User login
Novel oral antifungal headed to phase III for onychomycosis
VIENNA – A once-weekly oral antifungal drug known as VT-1161 will move into phase III clinical testing in 2017 based on its impressive performance in an interim analysis of a phase IIb study, Amir Tavakkol, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“We saw robust evidence of clinical and mycologic efficacy in patients with moderate to severe onychomycosis. This was true even in patients with nails considered very difficult to treat because of dermatophytomas and spikes, which are usually poor prognostic elements,” said Dr. Tavakkol, chief development officer at Viamet Pharmaceuticals in Durham, N.C., which is developing VT-1161.
He reported on 107 patients with toenail onychomycosis who enrolled in the phase IIb, double-blind, placebo-controlled RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study. At enrollment they averaged 47% disease involvement of the big toenail, the target nail for the trial. Participants in the five study arms had an average of 4.2-5.0 affected toenails. Both the percentage of nail involvement and the number of diseased toenails were roughly twice as great as is typical in studies of topical antifungals, underscoring that participants in the VT-1161 trial had fairly severe onychomycosis.
Patients were assigned to one of five study arms: 300 mg of VT-1161 once weekly for 12 weeks, then 12 weeks of placebo; 600 mg of VT-1161 once weekly for 12 weeks, followed by 12 weeks of placebo; either 300 or 600 mg of the antifungal agent once weekly for the full 24 weeks; or 24 weeks of once-per-week placebo. Immediately prior to the formal start of the study, however, everyone received 14 days of a once-daily loading dose of VT-1161 or placebo at the dose they would subsequently take once weekly during the trial.
The primary outcome in the ongoing study is the percentage of patients with a complete cure, both mycologic and clinical, at 48 weeks. Those data aren’t in yet, but Dr. Tavakkol presented the results of the prespecified interim analysis at 24 weeks. 
“Please keep in mind that this is only at most 24 weeks of therapy. Given the rate of nail growth at 1 mm per month when it is healthy, these are remarkable data. Ten percent or less nail involvement is basically 1-2 mm at the distal end. I believe a substantial percentage of these patients will reach clinical cure by 48 weeks,” he said.
VT-1161, a molecule with high selectivity for fungal CYP51, blocks the production of ergosterol, a key component of the fungal cell membrane, according to the company. It has no known drug interactions. At all doses studied in the trial, it was safe and well tolerated, with no abnormal liver function tests, no effect on bilirubin, and no change in QTc interval. Only 8 of the 107 patients reported adverse events deemed possibly related to the study drug by blinded investigators. No one dropped out of the study.
“VT-1161 is also being developed for recurrent vulvovaginal candidiasis. The results there are outstanding, too,” Dr. Tavakkol said.
The trial was funded by Viamet, where he is employed.
VIENNA – A once-weekly oral antifungal drug known as VT-1161 will move into phase III clinical testing in 2017 based on its impressive performance in an interim analysis of a phase IIb study, Amir Tavakkol, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“We saw robust evidence of clinical and mycologic efficacy in patients with moderate to severe onychomycosis. This was true even in patients with nails considered very difficult to treat because of dermatophytomas and spikes, which are usually poor prognostic elements,” said Dr. Tavakkol, chief development officer at Viamet Pharmaceuticals in Durham, N.C., which is developing VT-1161.
He reported on 107 patients with toenail onychomycosis who enrolled in the phase IIb, double-blind, placebo-controlled RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study. At enrollment they averaged 47% disease involvement of the big toenail, the target nail for the trial. Participants in the five study arms had an average of 4.2-5.0 affected toenails. Both the percentage of nail involvement and the number of diseased toenails were roughly twice as great as is typical in studies of topical antifungals, underscoring that participants in the VT-1161 trial had fairly severe onychomycosis.
Patients were assigned to one of five study arms: 300 mg of VT-1161 once weekly for 12 weeks, then 12 weeks of placebo; 600 mg of VT-1161 once weekly for 12 weeks, followed by 12 weeks of placebo; either 300 or 600 mg of the antifungal agent once weekly for the full 24 weeks; or 24 weeks of once-per-week placebo. Immediately prior to the formal start of the study, however, everyone received 14 days of a once-daily loading dose of VT-1161 or placebo at the dose they would subsequently take once weekly during the trial.
The primary outcome in the ongoing study is the percentage of patients with a complete cure, both mycologic and clinical, at 48 weeks. Those data aren’t in yet, but Dr. Tavakkol presented the results of the prespecified interim analysis at 24 weeks.
“Please keep in mind that this is only at most 24 weeks of therapy. Given the rate of nail growth at 1 mm per month when it is healthy, these are remarkable data. Ten percent or less nail involvement is basically 1-2 mm at the distal end. I believe a substantial percentage of these patients will reach clinical cure by 48 weeks,” he said.
VT-1161, a molecule with high selectivity for fungal CYP51, blocks the production of ergosterol, a key component of the fungal cell membrane, according to the company. It has no known drug interactions. At all doses studied in the trial, it was safe and well tolerated, with no abnormal liver function tests, no effect on bilirubin, and no change in QTc interval. Only 8 of the 107 patients reported adverse events deemed possibly related to the study drug by blinded investigators. No one dropped out of the study.
“VT-1161 is also being developed for recurrent vulvovaginal candidiasis. The results there are outstanding, too,” Dr. Tavakkol said.
The trial was funded by Viamet, where he is employed.
VIENNA – A once-weekly oral antifungal drug known as VT-1161 will move into phase III clinical testing in 2017 based on its impressive performance in an interim analysis of a phase IIb study, Amir Tavakkol, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
“We saw robust evidence of clinical and mycologic efficacy in patients with moderate to severe onychomycosis. This was true even in patients with nails considered very difficult to treat because of dermatophytomas and spikes, which are usually poor prognostic elements,” said Dr. Tavakkol, chief development officer at Viamet Pharmaceuticals in Durham, N.C., which is developing VT-1161.
He reported on 107 patients with toenail onychomycosis who enrolled in the phase IIb, double-blind, placebo-controlled RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study. At enrollment they averaged 47% disease involvement of the big toenail, the target nail for the trial. Participants in the five study arms had an average of 4.2-5.0 affected toenails. Both the percentage of nail involvement and the number of diseased toenails were roughly twice as great as is typical in studies of topical antifungals, underscoring that participants in the VT-1161 trial had fairly severe onychomycosis.
Patients were assigned to one of five study arms: 300 mg of VT-1161 once weekly for 12 weeks, then 12 weeks of placebo; 600 mg of VT-1161 once weekly for 12 weeks, followed by 12 weeks of placebo; either 300 or 600 mg of the antifungal agent once weekly for the full 24 weeks; or 24 weeks of once-per-week placebo. Immediately prior to the formal start of the study, however, everyone received 14 days of a once-daily loading dose of VT-1161 or placebo at the dose they would subsequently take once weekly during the trial.
The primary outcome in the ongoing study is the percentage of patients with a complete cure, both mycologic and clinical, at 48 weeks. Those data aren’t in yet, but Dr. Tavakkol presented the results of the prespecified interim analysis at 24 weeks.
“Please keep in mind that this is only at most 24 weeks of therapy. Given the rate of nail growth at 1 mm per month when it is healthy, these are remarkable data. Ten percent or less nail involvement is basically 1-2 mm at the distal end. I believe a substantial percentage of these patients will reach clinical cure by 48 weeks,” he said.
VT-1161, a molecule with high selectivity for fungal CYP51, blocks the production of ergosterol, a key component of the fungal cell membrane, according to the company. It has no known drug interactions. At all doses studied in the trial, it was safe and well tolerated, with no abnormal liver function tests, no effect on bilirubin, and no change in QTc interval. Only 8 of the 107 patients reported adverse events deemed possibly related to the study drug by blinded investigators. No one dropped out of the study.
“VT-1161 is also being developed for recurrent vulvovaginal candidiasis. The results there are outstanding, too,” Dr. Tavakkol said.
The trial was funded by Viamet, where he is employed.
AT THE EADV CONGRESS
Key clinical point:
Major finding: Among onychomycosis patients with an average 47% target toenail involvement at baseline, 35% had improved to no more than 10% nail involvement at 24 weeks after 12 weeks of once-weekly VT-1161 followed by 12 weeks of placebo.
Data source: A double-blind, randomized, phase IIb clinical trial involving 107 patients with toenail onychomycosis.
Disclosures: The trial was funded by Viamet Pharmaceuticals, where the study presenter is employed.
Oncolytic virus active against bladder cancer
NATIONAL HARBOR, MD – For patients with non-muscle invasive bladder cancer, intravesicular administration of an oncolytic virus was both feasible and safe, and in a small study was associated with at least one complete tumor response, investigators reported.
Instillation into the bladder of coxsackievirus A21 (CVA21; Cavatak), alone or in combination with low-dose mitomycin C, was associated with increases in immune cell filtrates and ramped-up expression of the programmed death-1 ligand (PD-L1) in the tumor microenvironment, reported Nicola Annels, PhD, a research fellow at the University of Surrey in England.
“Whilst the use of BCG [Bacille Calmette-Guerin] as an immunotherapy for non-muscle invasive bladder cancer has significantly improved disease-specific survival, the potential for serious side effects and local and systemic toxicity, together with the fact that there is a significant proportion of non-responding patients to BCG, highlights the need to develop future immune-based therapies to overcome these problems,” she said at the annual meeting of the Society for Immunotherapy of Cancer.
CVA21 is a proprietary formulation of coxsackievirus A21, a common cold virus. It targets intracellular adhesion molecule-1 (ICAM-1), and has been shown to have potent oncolytic activity against both non-muscle invasive bladder cancer (NMIBC) cell lines and ex vivo human bladder tumors. Delivering CVA21 with low-dose mitomycin C has been shown to enhance viral replication by increasing cell surface expression levels of ICAM-1, Dr. Annels noted.
In the stage I/II CANON study, the investigators studied the tolerability and safety of escalating doses of CVA21 alone or in combination with 10 mg mitomycin C in 16 patients with untreated NMIBC who were scheduled to undergo transurethral resection of bladder tumor (TURBT).
On serial cystoscopic photographs, the investigators saw evidence of anticancer activity including one complete response in one of three patients on CVA21 monotherapy at the highest of three doses, as well as virally-induced tumor inflammation.
Additional evidence of viral tumor targeting came from detection of secondary viral-load peaks in urine, and immunohistochemical analysis of tissues excised during TURBT, which tissue displayed tumor-specific viral replication and programmed cell death.
The authors also found that tissues treated with CVA21 showed upregulation of both interferon-response genes and immune checkpoint inhibitory genes compared with tissues from historical controls. This finding suggests that the antitumor effect of CVA21 might be enhanced by sequential administration of the virus followed by an immune checkpoint inhibitor, Dr. Annels said.
Patients tolerated the administration of CVA21 well, and there were no product-related adverse events greater than grade 1.
The activity observed thus “is likely to provide a strong signal in generating both a strong local and systemic anti-tumor response,” she said.
The study was funded by The Prostate Project, RingRose Foundation, Prostate Cancer UK, Topic of Cancer UK, Breast Cancer Campaign, the European Union, and Viralytics. Dr. Annels reported no conflicts of interest.
NATIONAL HARBOR, MD – For patients with non-muscle invasive bladder cancer, intravesicular administration of an oncolytic virus was both feasible and safe, and in a small study was associated with at least one complete tumor response, investigators reported.
Instillation into the bladder of coxsackievirus A21 (CVA21; Cavatak), alone or in combination with low-dose mitomycin C, was associated with increases in immune cell filtrates and ramped-up expression of the programmed death-1 ligand (PD-L1) in the tumor microenvironment, reported Nicola Annels, PhD, a research fellow at the University of Surrey in England.
“Whilst the use of BCG [Bacille Calmette-Guerin] as an immunotherapy for non-muscle invasive bladder cancer has significantly improved disease-specific survival, the potential for serious side effects and local and systemic toxicity, together with the fact that there is a significant proportion of non-responding patients to BCG, highlights the need to develop future immune-based therapies to overcome these problems,” she said at the annual meeting of the Society for Immunotherapy of Cancer.
CVA21 is a proprietary formulation of coxsackievirus A21, a common cold virus. It targets intracellular adhesion molecule-1 (ICAM-1), and has been shown to have potent oncolytic activity against both non-muscle invasive bladder cancer (NMIBC) cell lines and ex vivo human bladder tumors. Delivering CVA21 with low-dose mitomycin C has been shown to enhance viral replication by increasing cell surface expression levels of ICAM-1, Dr. Annels noted.
In the stage I/II CANON study, the investigators studied the tolerability and safety of escalating doses of CVA21 alone or in combination with 10 mg mitomycin C in 16 patients with untreated NMIBC who were scheduled to undergo transurethral resection of bladder tumor (TURBT).
On serial cystoscopic photographs, the investigators saw evidence of anticancer activity including one complete response in one of three patients on CVA21 monotherapy at the highest of three doses, as well as virally-induced tumor inflammation.
Additional evidence of viral tumor targeting came from detection of secondary viral-load peaks in urine, and immunohistochemical analysis of tissues excised during TURBT, which tissue displayed tumor-specific viral replication and programmed cell death.
The authors also found that tissues treated with CVA21 showed upregulation of both interferon-response genes and immune checkpoint inhibitory genes compared with tissues from historical controls. This finding suggests that the antitumor effect of CVA21 might be enhanced by sequential administration of the virus followed by an immune checkpoint inhibitor, Dr. Annels said.
Patients tolerated the administration of CVA21 well, and there were no product-related adverse events greater than grade 1.
The activity observed thus “is likely to provide a strong signal in generating both a strong local and systemic anti-tumor response,” she said.
The study was funded by The Prostate Project, RingRose Foundation, Prostate Cancer UK, Topic of Cancer UK, Breast Cancer Campaign, the European Union, and Viralytics. Dr. Annels reported no conflicts of interest.
NATIONAL HARBOR, MD – For patients with non-muscle invasive bladder cancer, intravesicular administration of an oncolytic virus was both feasible and safe, and in a small study was associated with at least one complete tumor response, investigators reported.
Instillation into the bladder of coxsackievirus A21 (CVA21; Cavatak), alone or in combination with low-dose mitomycin C, was associated with increases in immune cell filtrates and ramped-up expression of the programmed death-1 ligand (PD-L1) in the tumor microenvironment, reported Nicola Annels, PhD, a research fellow at the University of Surrey in England.
“Whilst the use of BCG [Bacille Calmette-Guerin] as an immunotherapy for non-muscle invasive bladder cancer has significantly improved disease-specific survival, the potential for serious side effects and local and systemic toxicity, together with the fact that there is a significant proportion of non-responding patients to BCG, highlights the need to develop future immune-based therapies to overcome these problems,” she said at the annual meeting of the Society for Immunotherapy of Cancer.
CVA21 is a proprietary formulation of coxsackievirus A21, a common cold virus. It targets intracellular adhesion molecule-1 (ICAM-1), and has been shown to have potent oncolytic activity against both non-muscle invasive bladder cancer (NMIBC) cell lines and ex vivo human bladder tumors. Delivering CVA21 with low-dose mitomycin C has been shown to enhance viral replication by increasing cell surface expression levels of ICAM-1, Dr. Annels noted.
In the stage I/II CANON study, the investigators studied the tolerability and safety of escalating doses of CVA21 alone or in combination with 10 mg mitomycin C in 16 patients with untreated NMIBC who were scheduled to undergo transurethral resection of bladder tumor (TURBT).
On serial cystoscopic photographs, the investigators saw evidence of anticancer activity including one complete response in one of three patients on CVA21 monotherapy at the highest of three doses, as well as virally-induced tumor inflammation.
Additional evidence of viral tumor targeting came from detection of secondary viral-load peaks in urine, and immunohistochemical analysis of tissues excised during TURBT, which tissue displayed tumor-specific viral replication and programmed cell death.
The authors also found that tissues treated with CVA21 showed upregulation of both interferon-response genes and immune checkpoint inhibitory genes compared with tissues from historical controls. This finding suggests that the antitumor effect of CVA21 might be enhanced by sequential administration of the virus followed by an immune checkpoint inhibitor, Dr. Annels said.
Patients tolerated the administration of CVA21 well, and there were no product-related adverse events greater than grade 1.
The activity observed thus “is likely to provide a strong signal in generating both a strong local and systemic anti-tumor response,” she said.
The study was funded by The Prostate Project, RingRose Foundation, Prostate Cancer UK, Topic of Cancer UK, Breast Cancer Campaign, the European Union, and Viralytics. Dr. Annels reported no conflicts of interest.
AT SITC 2016
Key clinical point:. Intravesicular coxsackievirus A21 (CVA21) showed good activity and safety against non-muscle invasive bladder cancer (NMIBC).
Major finding: One of three patients on the highest dose of CVA21 had a complete tumor response.
Data source: Phase I/II dose escalation and safety study in 16 patients with untreated NMIBC before surgery.
Disclosures: The study was funded by The Prostate Project, RingRose Foundation, Prostate Cancer UK, Topic of Cancer UK, Breast Cancer Campaign, the European Union, and Viralytics. Dr. Annels reported no conflicts of interest.
2016 Update on bone health
Prioritize bone health, as osteoporotic fracture is a major source of morbidity and mortality among women. In this article: fracture risk with OC use in perimenopause, data that inform calcium’s role in cardiovascular disease, sarcopenia management, and an emerging treatment.
Most women’s health care providers are aware of recent changes and controversies regarding cervical cancer screening, mammography frequency, and whether a pelvic bimanual exam should be part of our annual well woman evaluation.1 However, I believe one of the most important things we as clinicians can do is be frontline in promoting bone health. Osteoporotic fracture is a major source of morbidity and mortality.2,3 Thus, promoting the maintenance of bone health is a priority in my own practice. It is also one of my many academic interests.
What follows is an update on bone health. In past years, this update has been entitled, “Update on osteoporosis,” but what we are trying to accomplish is fracture reduction. Thus, priorities for bone health consist of recognition of risk, lifestyle and dietary counseling, as well as the use of pharmacologic agents when appropriate. Certain research stands out as informative for your practice:
- a recent study on the risk of fracture with oral contraceptive (OC) use in perimenopause
- 3 just-published studies that inform our understanding of calcium’s role in cardiovascular health
- a review on sarcopenia management
- new data on romosozumab.
Oral contraceptive use in perimenopause
Scholes D, LaCroix AZ, Hubbard RA, et al. Oral contraceptive use and fracture risk around the menopausal transition. Menopause. 2016;23(2):166-174.
The use of OCs in women of older reproductive age has increased ever since the cutoff age of 35 years was eliminated.4 Lower doses have continued to be utilized in these "older" women with excellent control of irregular bleeding due to ovulatory dysfunction (and reduction in psychosocial symptoms as well).5
The effect of OC use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, Scholes and colleagues conducted a population-based case-controlled study in a Pacific Northwest HMO, Group Health Cooperative.
Details of the study
Scholes and colleagues enrolled 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs).
Participation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases and controls for OC use:
- in the 10 years before menopause (OR, 0.90; 95% CI, 0.74-1.11)
- after age 38 years (OR, 0.94; 95% CI, 0.78-1.14)
- over the duration, or
- for other OC exposures.
Related article:
2016 Update on female sexual dysfunction
Association between fractures and OC use near menopause
The current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38 years. For women considering OC use at these times, fracture risk does not seem to be either reduced or increased.
These results, looking at fracture, seem to be further supported by trials conducted by Gambacciani and colleagues,6 in which researchers randomly assigned irregularly cycling perimenopausal women (aged 40-49 years) to 20 μg ethinyl estradiol OCs or calcium/placebo. Results showed that this low-dose OC use significantly increased bone density at the femoral neck, spine, and other sites relative to control women after 24 months.
In the current Scholes study, the use of OCs in the decade before menopause or after age 38 did not reduce fracture risk in the years around the time of menopause. It is reassuring that their use was not associated with any increased fracture risk.
These findings provide additional clarity and guidance to women and their clinicians at a time of increasing public health concern about fractures. For women who may choose to use OCs during late premenopause (around age 38-48 years), fracture risk around the menopausal transition will not differ from women not choosing this option.
Calcium and calcium supplements: The data continue to grow
Anderson JJ, Kruszka B, Delaney JA, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA) [published online ahead of print October 11, 2016]. J Am Heart Assoc. pii: e003815.
Billington EO, Bristow SM, Gamble GD, et al. Acute effects of calcium supplements on blood pressure: randomised, crossover trial in postmenopausal women [published online ahead of print August 20, 2016]. Osteoporos Int. doi:10.1007/s00198-016-3744-y.
Crandall CJ, Aragaki AK, LeBoff MS, et al. Calcium plus vitamin D supplementation and height loss: findings from the Women's Health Initiative Calcium and Vitamin D clinical trial [published online ahead of print August 1, 2016]. Menopause. doi:10.1097 /GME.0000000000000704.
In 2001, a National Institutes of Health (NIH) Consensus Development Panel on osteoporosis concluded that calcium intake is crucial to maintain bone mass and should be maintained at 1,000-1,500 mg/day in older adults. The panel acknowledged that the majority of older adults did not meet the recommended intake from dietary sources alone, and therefore would require calcium supplementation. Calcium supplements are one of the most commonly used dietary supplements, and population-based surveys have shown that they are used by the majority of older men and women in the United States.7
More recently results from large randomized controlled trials (RCTs) of calcium supplements have been reported, leading to concerns about calcium efficacy for fracture risk and safety. Bolland and colleagues8 reported that calcium supplements increased the rate of cardiovascular events in healthy older women and suggested that their role in osteoporosis management be reconsidered. More recently, the US Preventive Services Task Force recommended against calcium supplements for the primary prevention of fractures in noninstitutionalized postmenopausal women.9
The association between calcium intake and CVD events
Anderson and colleagues acknowledged that recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, they assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC).
Details of the study by Anderson and colleagues
The authors studied 5,448 adults free of clinically diagnosed CVD (52% female; age range, 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles based on overall population distribution. Baseline CAC was measured by computed tomography (CT) scan, and CAC measurements were repeated in 2,742 participants approximately 10 years later. Women had higher calcium intakes than men.
After adjustment for potential confounders, among 1,567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake is included in the TABLE. After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR, 1.22; 95% CI, 1.07-1.39). No relation was found between baseline calcium intake and 10-year changes in CAC among those participants with baseline CAC less than zero.
They concluded that high total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.
Related article:
Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
Calcium supplements and blood pressure
Billington and colleagues acknowledged that calcium supplements appear to increase cardiovascular risk but that the mechanism is unknown. They had previously reported that blood pressure declines over the course of the day in older women.10
Details of the study by Billington and colleagues
In this new study the investigators examined the acute effects of calcium supplements on blood pressure in a randomized controlled crossover trial in 40 healthy postmenopausal women (mean age, 71 years; body mass index [BMI], 27.2 kg/m2). Women attended on 2 occasions, with visits separated by 7 or more days. At each visit, they received either 1 g of calcium as citrate or placebo. Blood pressure and serum calcium concentrations were measured immediately before and 2, 4, and 6 hours after each intervention.
Ionized and total calcium concentrations increased after calcium (P<.0001 vs placebo). Systolic blood pressure (SBP) measurements decreased after both calcium and placebo but significantly less so after calcium (P=.02). The reduction in SBP from baseline was smaller after calcium compared with placebo by 6 mm Hg at 4 hours (P=.036) and by 9 mm Hg at 6 hours (P=.002). The reduction in diastolic blood pressure was similar after calcium and placebo.
These findings indicate that the use of calcium supplements in postmenopausal women attenuates the postbreakfast reduction in SBP by 6 to 9 mm Hg. Whether these changes in blood pressure influence cardiovascular risk requires further study.
Association between calcium, vitamin D, and height loss
Crandall and colleagues looked at the association between calcium and vitamin D supplementation and height loss in 36,282 participants of the Women's Health Initiative Calcium and Vitamin D trial.
Details of the study by Crandall and colleagues
The authors performed a post hoc analysis of data from a double-blind randomized controlled trial of 1,000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily (CaD) or placebo in postmenopausal women at 40 US clinical centers. Height was measured annually (mean follow-up, 5.9 years) with a stadiometer.
Average height loss was 1.28 mm/yr among participants assigned to CaD, versus 1.26 mm/yr for women assigned to placebo (P=.35). A strong association (P<.001) was observed between age group and height loss. The study authors concluded that, compared with placebo, calcium and vitamin D supplementation used in this trial did not prevent height loss in healthy postmenopausal women.
Adequate calcium is necessary for bone health. While calcium supplementation may not be adequate to prevent fractures, it is also not involved in the inevitable loss of overall height seen in postmenopausal women. Calcium supplementation has been implicated in an increase in CVD. These data seem to indicate that, while calcium supplementation results in higher systolic blood pressure during the day, as well as higher coronary artery calcium scores, greater dietary calcium actually may decrease the incidence of atherosclerosis.
Sarcopenia: Still important, clinical approaches to easily detect it
Beaudart C, McCloskey E, Bruyére O, et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 2016;16(1):170.
In last year's update, I reviewed the article by He and colleagues11 on the relationship between sarcopenia and body composition with osteoporosis. Sarcopenia, which is the age-related loss of muscle mass and strength, is important to address in patients. Body composition and muscle strength are directly correlated with bone density, and this is not surprising since bone and muscle share some common hormonal, genetic, nutritional, and lifestyle determinants.12,13 Sarcopenia can be diagnosed via dual-energy x-ray absorptiometry (DXA) scan looking at lean muscle mass.
The term sarcopenia was first coined by Rosenberg and colleagues in 198914 as a progressive loss of skeletal muscle mass with advancing age. Since then, the definition has expanded to incorporate the notion of impaired muscle strength or physical performance. Sarcopenia is associated with morbidity and mortality from linked physical disability, falls, fractures, poor quality of life, depression, and hospitalization.15
Current research is focusing on nutritional exercise/activity-based and other novel interventions for improving the quality and quantity of skeletal muscle in older people. Some studies demonstrated that resistance training combined with nutritional supplements can improve muscle function.16
Details of the study
Beaudart and colleagues propose some user-friendly and inexpensive methods that can be utilized to assess sarcopenia in real life settings. They acknowledge that in research settings or even specialist clinical settings, DXA or computed tomography (CT) scans are the best assessment of muscle mass.
Anthropometric measurements. In a primary care setting, anthropometric measurement, especially calf circumference and mid-upper arm muscle circumference, correlate with overall muscle mass and reflect both health and nutritional status and predict performance, health, and survival in older people.
However, with advancing age, changes in the distribution of fat and loss of skin elasticity are such that circumference incurs a loss of accuracy and precision in older people. Some studies suggest that an adjustment of anthropometric measurements for age, sex, or BMI results in a better correlation with DXA-measured lean mass.17 Anthropometric measurements are simple clinical prediction tools that can be easily applied for sarcopenia since they offer the most portable, commonly applicable, inexpensive, and noninvasive technique for assessing size, proportions, and composition of the human body. However, their validity is limited when applied to individuals because cutoff points to identify low muscle mass still need to be defined. Still, serial measurements in a patient over time may be valuable.
Related article:
2014 Update on osteoporosis
Handgrip strength, as measured with a dynamometer, appears to be the most widely used method for the measurement of muscle strength. In general, isometric handgrip strength shows a good correlation with leg strength and also with lower extremity power, and calf cross-sectional muscle area. The measurement is easy to perform, inexpensive and does not require a specialist-trained staff.
Standardized conditions for the test include seating the patient in a standard chair with her forearms resting flat on the chair arms. Clinicians should demonstrate the use of the dynamometer and show that gripping very tightly registers the best score. Six measurements should be taken, 3 with each arm. Ideally, patients should be encouraged to squeeze as hard and tightly as possible during 3 to 5 seconds for each of the 6 trials; usually the highest reading of the 6 measurements is reported as the final result. The Jamar dynamometer, or similar hydraulic dynamometer, is the gold standard for this measurement.
Gait speed measurement. The most widely used tool in clinical practice for the assessment of physical performance is the gait speed measurement. The test is highly acceptable for participants and health professionals in clinical settings. No special equipment is required; it needs only a flat floor devoid of obstacles. In the 4-meter gait speed test, men and women with a gait speed of less than 0.8 meters/sec are described as having a poor physical performance. The average extra time added to the consultation by measuring the 4-meter gait speed was only 95 seconds (SD, 20 seconds).
Loss of muscle mass correlates with loss of bone mass as our patients age. In addition, such sarcopenia increases the risk of falls, a significant component of the rising rate of fragility fractures. Anthropometric measures, grip strength, and gait speed are easy, low-cost measures that can identify patients at increased risk.
Romosozumab: An interesting new agent to look forward to
Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532-1543.
Romosozumab is a monoclonal antibody that binds sclerostin, increasing bone formation and decreasing bone resorption. Cosman and colleagues enrolled 7,180 postmenopausal women with a T score of -2.5 to -3.5 at the total hip or femoral neck. Participants were randomly assigned to receive subcutaneous injections of romosozumab 210 mg or placebo monthly for 12 months. Thereafter, women in each group received subcutaneous denosumab 60 mg for 12 months--administered every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 and 24 months. Secondary end points included clinical and nonvertebral fractures.
Details of the study
At 12 months, new vertebral fractures had occurred in 16 of 3,321 women (0.5%) in the romosozumab group, as compared with 59 of 3,322 (1.8%) in the placebo group (representing a 73% lower risk of fracture with romosozumab; P<.001). Clinical fractures had occurred in 58 of 3,589 women (1.6%) in the romosozumab group, as compared with 90 of 3,591 (2.5%) in the placebo group (a 36% lower fracture risk with romosozumab; P = .008). Nonvertebral fractures had occurred in 56 of 3,589 women (1.6%) in the romosozumab group and in 75 of 3,591 (2.1%) in the placebo group (P = .10).
At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3,325 women] in the romosozumab group vs 2.5% [84 of 3,327 women] in the placebo group, a 75% lower risk with romosozumab; P<.001). Adverse events, including cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and 2 cases of osteonecrosis of the jaw were observed in the romosozumab group.
Lower risk of fracture
Thus, in postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year.
Of note, the effect of romosozumab on the risk of vertebral fracture was rapid, with only 2 additional vertebral fractures (of a total of 16 such fractures in the romosozumab group) occurring in the second 6 months of the first year of therapy. Because vertebral and clinical fractures are associated with increased morbidity and considerable health care costs, a treatment that would reduce this risk rapidly could offer appropriate patients an important benefit.
Romosozumab is a new agent. Though not yet available, it is extremely interesting because it not only decreases bone resorption but also increases bone formation. The results of this large prospective trial show that such an agent reduces both vertebral and clinical fracture and reduces that fracture risk quite rapidly within the first 6 months of therapy.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- MacLaughlin KL, Faubion SS, Long ME, Pruthi S, Casey PM. Should the annual pelvic examination go the way of annual cervical cytology? Womens Health (Lond). 2014;10(4):373–384.
- Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520–2526.
- Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King AB, Tosterson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 2007;22(3):465–475.
- Kaunitz AM. Hormonal contraception in women of older reproductive age. N Engl J Med. 2008;358:1262–1270.
- Kaunitz AM. Oral contraceptive use in perimenopause. Am J Obstet Gynecol. 2001;185(2 suppl):S32–S37.
- Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54(2):176–180.
- Bailey R, Dodd K, Goldman J, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140(4):817–822.
- Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013;4(5):199–210.
- Moyer VA; U.S. Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158(9):691–696.
- Bristow SM, Gamble GD, Stewart A, Horne AM, Reid IR. Acute effects of calcium supplements on blood pressure and blood coagulation: secondary analysis of a randomised controlled trial in post-menopausal women. Br J Nutr. 2015;114(11):1868–1874.
- He H, Liu Y, Tian Q, Papasian CJ, Hu T, Deng HW. Relationship of sarcopenia and body composition with osteoporosis. Osteoporos Int. 2016;27(2):473–482.
- Coin A, Perissinotto E, Enzi G, et al. Predictors of low bone mineral density in the elderly: the role of dietary intake, nutritional status and sarcopenia. Eur J Clin Nutr. 2008;62(6):802–809.
- Taaffe DR, Cauley JA, Danielson M, et al. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study. J Bone Miner Res. 2001;16(7):1343–1352.
- Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 suppl):990S–991S.
- Beaudart C, Rizzoli R, Bruyere O, Reginster JY, Biver E. Sarcopenia: Burden and challenges for Public Health. Arch Public Health. 2014;72(1):45.
- Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–759.
- Kulkarni B, Kuper H, Taylor A, et al. Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women. J Appl Physiol. 2013;115(8):1156–1162.
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York University School of Medicine, and Director of Gynecologic Ultrasound and Co-Director of Bone Densitometry and Body Composition at New York University Medical Center in New York, New York. He serves on the OBG
The author reports no financial relationships relevant to this article.
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York University School of Medicine, and Director of Gynecologic Ultrasound and Co-Director of Bone Densitometry and Body Composition at New York University Medical Center in New York, New York. He serves on the OBG
The author reports no financial relationships relevant to this article.
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York University School of Medicine, and Director of Gynecologic Ultrasound and Co-Director of Bone Densitometry and Body Composition at New York University Medical Center in New York, New York. He serves on the OBG
The author reports no financial relationships relevant to this article.
Prioritize bone health, as osteoporotic fracture is a major source of morbidity and mortality among women. In this article: fracture risk with OC use in perimenopause, data that inform calcium’s role in cardiovascular disease, sarcopenia management, and an emerging treatment.
Most women’s health care providers are aware of recent changes and controversies regarding cervical cancer screening, mammography frequency, and whether a pelvic bimanual exam should be part of our annual well woman evaluation.1 However, I believe one of the most important things we as clinicians can do is be frontline in promoting bone health. Osteoporotic fracture is a major source of morbidity and mortality.2,3 Thus, promoting the maintenance of bone health is a priority in my own practice. It is also one of my many academic interests.
What follows is an update on bone health. In past years, this update has been entitled, “Update on osteoporosis,” but what we are trying to accomplish is fracture reduction. Thus, priorities for bone health consist of recognition of risk, lifestyle and dietary counseling, as well as the use of pharmacologic agents when appropriate. Certain research stands out as informative for your practice:
- a recent study on the risk of fracture with oral contraceptive (OC) use in perimenopause
- 3 just-published studies that inform our understanding of calcium’s role in cardiovascular health
- a review on sarcopenia management
- new data on romosozumab.
Oral contraceptive use in perimenopause
Scholes D, LaCroix AZ, Hubbard RA, et al. Oral contraceptive use and fracture risk around the menopausal transition. Menopause. 2016;23(2):166-174.
The use of OCs in women of older reproductive age has increased ever since the cutoff age of 35 years was eliminated.4 Lower doses have continued to be utilized in these "older" women with excellent control of irregular bleeding due to ovulatory dysfunction (and reduction in psychosocial symptoms as well).5
The effect of OC use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, Scholes and colleagues conducted a population-based case-controlled study in a Pacific Northwest HMO, Group Health Cooperative.
Details of the study
Scholes and colleagues enrolled 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs).
Participation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases and controls for OC use:
- in the 10 years before menopause (OR, 0.90; 95% CI, 0.74-1.11)
- after age 38 years (OR, 0.94; 95% CI, 0.78-1.14)
- over the duration, or
- for other OC exposures.
Related article:
2016 Update on female sexual dysfunction
Association between fractures and OC use near menopause
The current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38 years. For women considering OC use at these times, fracture risk does not seem to be either reduced or increased.
These results, looking at fracture, seem to be further supported by trials conducted by Gambacciani and colleagues,6 in which researchers randomly assigned irregularly cycling perimenopausal women (aged 40-49 years) to 20 μg ethinyl estradiol OCs or calcium/placebo. Results showed that this low-dose OC use significantly increased bone density at the femoral neck, spine, and other sites relative to control women after 24 months.
In the current Scholes study, the use of OCs in the decade before menopause or after age 38 did not reduce fracture risk in the years around the time of menopause. It is reassuring that their use was not associated with any increased fracture risk.
These findings provide additional clarity and guidance to women and their clinicians at a time of increasing public health concern about fractures. For women who may choose to use OCs during late premenopause (around age 38-48 years), fracture risk around the menopausal transition will not differ from women not choosing this option.
Calcium and calcium supplements: The data continue to grow
Anderson JJ, Kruszka B, Delaney JA, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA) [published online ahead of print October 11, 2016]. J Am Heart Assoc. pii: e003815.
Billington EO, Bristow SM, Gamble GD, et al. Acute effects of calcium supplements on blood pressure: randomised, crossover trial in postmenopausal women [published online ahead of print August 20, 2016]. Osteoporos Int. doi:10.1007/s00198-016-3744-y.
Crandall CJ, Aragaki AK, LeBoff MS, et al. Calcium plus vitamin D supplementation and height loss: findings from the Women's Health Initiative Calcium and Vitamin D clinical trial [published online ahead of print August 1, 2016]. Menopause. doi:10.1097 /GME.0000000000000704.
In 2001, a National Institutes of Health (NIH) Consensus Development Panel on osteoporosis concluded that calcium intake is crucial to maintain bone mass and should be maintained at 1,000-1,500 mg/day in older adults. The panel acknowledged that the majority of older adults did not meet the recommended intake from dietary sources alone, and therefore would require calcium supplementation. Calcium supplements are one of the most commonly used dietary supplements, and population-based surveys have shown that they are used by the majority of older men and women in the United States.7
More recently results from large randomized controlled trials (RCTs) of calcium supplements have been reported, leading to concerns about calcium efficacy for fracture risk and safety. Bolland and colleagues8 reported that calcium supplements increased the rate of cardiovascular events in healthy older women and suggested that their role in osteoporosis management be reconsidered. More recently, the US Preventive Services Task Force recommended against calcium supplements for the primary prevention of fractures in noninstitutionalized postmenopausal women.9
The association between calcium intake and CVD events
Anderson and colleagues acknowledged that recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, they assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC).
Details of the study by Anderson and colleagues
The authors studied 5,448 adults free of clinically diagnosed CVD (52% female; age range, 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles based on overall population distribution. Baseline CAC was measured by computed tomography (CT) scan, and CAC measurements were repeated in 2,742 participants approximately 10 years later. Women had higher calcium intakes than men.
After adjustment for potential confounders, among 1,567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake is included in the TABLE. After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR, 1.22; 95% CI, 1.07-1.39). No relation was found between baseline calcium intake and 10-year changes in CAC among those participants with baseline CAC less than zero.
They concluded that high total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.
Related article:
Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
Calcium supplements and blood pressure
Billington and colleagues acknowledged that calcium supplements appear to increase cardiovascular risk but that the mechanism is unknown. They had previously reported that blood pressure declines over the course of the day in older women.10
Details of the study by Billington and colleagues
In this new study the investigators examined the acute effects of calcium supplements on blood pressure in a randomized controlled crossover trial in 40 healthy postmenopausal women (mean age, 71 years; body mass index [BMI], 27.2 kg/m2). Women attended on 2 occasions, with visits separated by 7 or more days. At each visit, they received either 1 g of calcium as citrate or placebo. Blood pressure and serum calcium concentrations were measured immediately before and 2, 4, and 6 hours after each intervention.
Ionized and total calcium concentrations increased after calcium (P<.0001 vs placebo). Systolic blood pressure (SBP) measurements decreased after both calcium and placebo but significantly less so after calcium (P=.02). The reduction in SBP from baseline was smaller after calcium compared with placebo by 6 mm Hg at 4 hours (P=.036) and by 9 mm Hg at 6 hours (P=.002). The reduction in diastolic blood pressure was similar after calcium and placebo.
These findings indicate that the use of calcium supplements in postmenopausal women attenuates the postbreakfast reduction in SBP by 6 to 9 mm Hg. Whether these changes in blood pressure influence cardiovascular risk requires further study.
Association between calcium, vitamin D, and height loss
Crandall and colleagues looked at the association between calcium and vitamin D supplementation and height loss in 36,282 participants of the Women's Health Initiative Calcium and Vitamin D trial.
Details of the study by Crandall and colleagues
The authors performed a post hoc analysis of data from a double-blind randomized controlled trial of 1,000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily (CaD) or placebo in postmenopausal women at 40 US clinical centers. Height was measured annually (mean follow-up, 5.9 years) with a stadiometer.
Average height loss was 1.28 mm/yr among participants assigned to CaD, versus 1.26 mm/yr for women assigned to placebo (P=.35). A strong association (P<.001) was observed between age group and height loss. The study authors concluded that, compared with placebo, calcium and vitamin D supplementation used in this trial did not prevent height loss in healthy postmenopausal women.
Adequate calcium is necessary for bone health. While calcium supplementation may not be adequate to prevent fractures, it is also not involved in the inevitable loss of overall height seen in postmenopausal women. Calcium supplementation has been implicated in an increase in CVD. These data seem to indicate that, while calcium supplementation results in higher systolic blood pressure during the day, as well as higher coronary artery calcium scores, greater dietary calcium actually may decrease the incidence of atherosclerosis.
Sarcopenia: Still important, clinical approaches to easily detect it
Beaudart C, McCloskey E, Bruyére O, et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 2016;16(1):170.
In last year's update, I reviewed the article by He and colleagues11 on the relationship between sarcopenia and body composition with osteoporosis. Sarcopenia, which is the age-related loss of muscle mass and strength, is important to address in patients. Body composition and muscle strength are directly correlated with bone density, and this is not surprising since bone and muscle share some common hormonal, genetic, nutritional, and lifestyle determinants.12,13 Sarcopenia can be diagnosed via dual-energy x-ray absorptiometry (DXA) scan looking at lean muscle mass.
The term sarcopenia was first coined by Rosenberg and colleagues in 198914 as a progressive loss of skeletal muscle mass with advancing age. Since then, the definition has expanded to incorporate the notion of impaired muscle strength or physical performance. Sarcopenia is associated with morbidity and mortality from linked physical disability, falls, fractures, poor quality of life, depression, and hospitalization.15
Current research is focusing on nutritional exercise/activity-based and other novel interventions for improving the quality and quantity of skeletal muscle in older people. Some studies demonstrated that resistance training combined with nutritional supplements can improve muscle function.16
Details of the study
Beaudart and colleagues propose some user-friendly and inexpensive methods that can be utilized to assess sarcopenia in real life settings. They acknowledge that in research settings or even specialist clinical settings, DXA or computed tomography (CT) scans are the best assessment of muscle mass.
Anthropometric measurements. In a primary care setting, anthropometric measurement, especially calf circumference and mid-upper arm muscle circumference, correlate with overall muscle mass and reflect both health and nutritional status and predict performance, health, and survival in older people.
However, with advancing age, changes in the distribution of fat and loss of skin elasticity are such that circumference incurs a loss of accuracy and precision in older people. Some studies suggest that an adjustment of anthropometric measurements for age, sex, or BMI results in a better correlation with DXA-measured lean mass.17 Anthropometric measurements are simple clinical prediction tools that can be easily applied for sarcopenia since they offer the most portable, commonly applicable, inexpensive, and noninvasive technique for assessing size, proportions, and composition of the human body. However, their validity is limited when applied to individuals because cutoff points to identify low muscle mass still need to be defined. Still, serial measurements in a patient over time may be valuable.
Related article:
2014 Update on osteoporosis
Handgrip strength, as measured with a dynamometer, appears to be the most widely used method for the measurement of muscle strength. In general, isometric handgrip strength shows a good correlation with leg strength and also with lower extremity power, and calf cross-sectional muscle area. The measurement is easy to perform, inexpensive and does not require a specialist-trained staff.
Standardized conditions for the test include seating the patient in a standard chair with her forearms resting flat on the chair arms. Clinicians should demonstrate the use of the dynamometer and show that gripping very tightly registers the best score. Six measurements should be taken, 3 with each arm. Ideally, patients should be encouraged to squeeze as hard and tightly as possible during 3 to 5 seconds for each of the 6 trials; usually the highest reading of the 6 measurements is reported as the final result. The Jamar dynamometer, or similar hydraulic dynamometer, is the gold standard for this measurement.
Gait speed measurement. The most widely used tool in clinical practice for the assessment of physical performance is the gait speed measurement. The test is highly acceptable for participants and health professionals in clinical settings. No special equipment is required; it needs only a flat floor devoid of obstacles. In the 4-meter gait speed test, men and women with a gait speed of less than 0.8 meters/sec are described as having a poor physical performance. The average extra time added to the consultation by measuring the 4-meter gait speed was only 95 seconds (SD, 20 seconds).
Loss of muscle mass correlates with loss of bone mass as our patients age. In addition, such sarcopenia increases the risk of falls, a significant component of the rising rate of fragility fractures. Anthropometric measures, grip strength, and gait speed are easy, low-cost measures that can identify patients at increased risk.
Romosozumab: An interesting new agent to look forward to
Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532-1543.
Romosozumab is a monoclonal antibody that binds sclerostin, increasing bone formation and decreasing bone resorption. Cosman and colleagues enrolled 7,180 postmenopausal women with a T score of -2.5 to -3.5 at the total hip or femoral neck. Participants were randomly assigned to receive subcutaneous injections of romosozumab 210 mg or placebo monthly for 12 months. Thereafter, women in each group received subcutaneous denosumab 60 mg for 12 months--administered every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 and 24 months. Secondary end points included clinical and nonvertebral fractures.
Details of the study
At 12 months, new vertebral fractures had occurred in 16 of 3,321 women (0.5%) in the romosozumab group, as compared with 59 of 3,322 (1.8%) in the placebo group (representing a 73% lower risk of fracture with romosozumab; P<.001). Clinical fractures had occurred in 58 of 3,589 women (1.6%) in the romosozumab group, as compared with 90 of 3,591 (2.5%) in the placebo group (a 36% lower fracture risk with romosozumab; P = .008). Nonvertebral fractures had occurred in 56 of 3,589 women (1.6%) in the romosozumab group and in 75 of 3,591 (2.1%) in the placebo group (P = .10).
At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3,325 women] in the romosozumab group vs 2.5% [84 of 3,327 women] in the placebo group, a 75% lower risk with romosozumab; P<.001). Adverse events, including cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and 2 cases of osteonecrosis of the jaw were observed in the romosozumab group.
Lower risk of fracture
Thus, in postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year.
Of note, the effect of romosozumab on the risk of vertebral fracture was rapid, with only 2 additional vertebral fractures (of a total of 16 such fractures in the romosozumab group) occurring in the second 6 months of the first year of therapy. Because vertebral and clinical fractures are associated with increased morbidity and considerable health care costs, a treatment that would reduce this risk rapidly could offer appropriate patients an important benefit.
Romosozumab is a new agent. Though not yet available, it is extremely interesting because it not only decreases bone resorption but also increases bone formation. The results of this large prospective trial show that such an agent reduces both vertebral and clinical fracture and reduces that fracture risk quite rapidly within the first 6 months of therapy.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Prioritize bone health, as osteoporotic fracture is a major source of morbidity and mortality among women. In this article: fracture risk with OC use in perimenopause, data that inform calcium’s role in cardiovascular disease, sarcopenia management, and an emerging treatment.
Most women’s health care providers are aware of recent changes and controversies regarding cervical cancer screening, mammography frequency, and whether a pelvic bimanual exam should be part of our annual well woman evaluation.1 However, I believe one of the most important things we as clinicians can do is be frontline in promoting bone health. Osteoporotic fracture is a major source of morbidity and mortality.2,3 Thus, promoting the maintenance of bone health is a priority in my own practice. It is also one of my many academic interests.
What follows is an update on bone health. In past years, this update has been entitled, “Update on osteoporosis,” but what we are trying to accomplish is fracture reduction. Thus, priorities for bone health consist of recognition of risk, lifestyle and dietary counseling, as well as the use of pharmacologic agents when appropriate. Certain research stands out as informative for your practice:
- a recent study on the risk of fracture with oral contraceptive (OC) use in perimenopause
- 3 just-published studies that inform our understanding of calcium’s role in cardiovascular health
- a review on sarcopenia management
- new data on romosozumab.
Oral contraceptive use in perimenopause
Scholes D, LaCroix AZ, Hubbard RA, et al. Oral contraceptive use and fracture risk around the menopausal transition. Menopause. 2016;23(2):166-174.
The use of OCs in women of older reproductive age has increased ever since the cutoff age of 35 years was eliminated.4 Lower doses have continued to be utilized in these "older" women with excellent control of irregular bleeding due to ovulatory dysfunction (and reduction in psychosocial symptoms as well).5
The effect of OC use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, Scholes and colleagues conducted a population-based case-controlled study in a Pacific Northwest HMO, Group Health Cooperative.
Details of the study
Scholes and colleagues enrolled 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs).
Participation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases and controls for OC use:
- in the 10 years before menopause (OR, 0.90; 95% CI, 0.74-1.11)
- after age 38 years (OR, 0.94; 95% CI, 0.78-1.14)
- over the duration, or
- for other OC exposures.
Related article:
2016 Update on female sexual dysfunction
Association between fractures and OC use near menopause
The current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38 years. For women considering OC use at these times, fracture risk does not seem to be either reduced or increased.
These results, looking at fracture, seem to be further supported by trials conducted by Gambacciani and colleagues,6 in which researchers randomly assigned irregularly cycling perimenopausal women (aged 40-49 years) to 20 μg ethinyl estradiol OCs or calcium/placebo. Results showed that this low-dose OC use significantly increased bone density at the femoral neck, spine, and other sites relative to control women after 24 months.
In the current Scholes study, the use of OCs in the decade before menopause or after age 38 did not reduce fracture risk in the years around the time of menopause. It is reassuring that their use was not associated with any increased fracture risk.
These findings provide additional clarity and guidance to women and their clinicians at a time of increasing public health concern about fractures. For women who may choose to use OCs during late premenopause (around age 38-48 years), fracture risk around the menopausal transition will not differ from women not choosing this option.
Calcium and calcium supplements: The data continue to grow
Anderson JJ, Kruszka B, Delaney JA, et al. Calcium intake from diet and supplements and the risk of coronary artery calcification and its progression among older adults: 10-year follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA) [published online ahead of print October 11, 2016]. J Am Heart Assoc. pii: e003815.
Billington EO, Bristow SM, Gamble GD, et al. Acute effects of calcium supplements on blood pressure: randomised, crossover trial in postmenopausal women [published online ahead of print August 20, 2016]. Osteoporos Int. doi:10.1007/s00198-016-3744-y.
Crandall CJ, Aragaki AK, LeBoff MS, et al. Calcium plus vitamin D supplementation and height loss: findings from the Women's Health Initiative Calcium and Vitamin D clinical trial [published online ahead of print August 1, 2016]. Menopause. doi:10.1097 /GME.0000000000000704.
In 2001, a National Institutes of Health (NIH) Consensus Development Panel on osteoporosis concluded that calcium intake is crucial to maintain bone mass and should be maintained at 1,000-1,500 mg/day in older adults. The panel acknowledged that the majority of older adults did not meet the recommended intake from dietary sources alone, and therefore would require calcium supplementation. Calcium supplements are one of the most commonly used dietary supplements, and population-based surveys have shown that they are used by the majority of older men and women in the United States.7
More recently results from large randomized controlled trials (RCTs) of calcium supplements have been reported, leading to concerns about calcium efficacy for fracture risk and safety. Bolland and colleagues8 reported that calcium supplements increased the rate of cardiovascular events in healthy older women and suggested that their role in osteoporosis management be reconsidered. More recently, the US Preventive Services Task Force recommended against calcium supplements for the primary prevention of fractures in noninstitutionalized postmenopausal women.9
The association between calcium intake and CVD events
Anderson and colleagues acknowledged that recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, they assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC).
Details of the study by Anderson and colleagues
The authors studied 5,448 adults free of clinically diagnosed CVD (52% female; age range, 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles based on overall population distribution. Baseline CAC was measured by computed tomography (CT) scan, and CAC measurements were repeated in 2,742 participants approximately 10 years later. Women had higher calcium intakes than men.
After adjustment for potential confounders, among 1,567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake is included in the TABLE. After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR, 1.22; 95% CI, 1.07-1.39). No relation was found between baseline calcium intake and 10-year changes in CAC among those participants with baseline CAC less than zero.
They concluded that high total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC.
Related article:
Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
Calcium supplements and blood pressure
Billington and colleagues acknowledged that calcium supplements appear to increase cardiovascular risk but that the mechanism is unknown. They had previously reported that blood pressure declines over the course of the day in older women.10
Details of the study by Billington and colleagues
In this new study the investigators examined the acute effects of calcium supplements on blood pressure in a randomized controlled crossover trial in 40 healthy postmenopausal women (mean age, 71 years; body mass index [BMI], 27.2 kg/m2). Women attended on 2 occasions, with visits separated by 7 or more days. At each visit, they received either 1 g of calcium as citrate or placebo. Blood pressure and serum calcium concentrations were measured immediately before and 2, 4, and 6 hours after each intervention.
Ionized and total calcium concentrations increased after calcium (P<.0001 vs placebo). Systolic blood pressure (SBP) measurements decreased after both calcium and placebo but significantly less so after calcium (P=.02). The reduction in SBP from baseline was smaller after calcium compared with placebo by 6 mm Hg at 4 hours (P=.036) and by 9 mm Hg at 6 hours (P=.002). The reduction in diastolic blood pressure was similar after calcium and placebo.
These findings indicate that the use of calcium supplements in postmenopausal women attenuates the postbreakfast reduction in SBP by 6 to 9 mm Hg. Whether these changes in blood pressure influence cardiovascular risk requires further study.
Association between calcium, vitamin D, and height loss
Crandall and colleagues looked at the association between calcium and vitamin D supplementation and height loss in 36,282 participants of the Women's Health Initiative Calcium and Vitamin D trial.
Details of the study by Crandall and colleagues
The authors performed a post hoc analysis of data from a double-blind randomized controlled trial of 1,000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily (CaD) or placebo in postmenopausal women at 40 US clinical centers. Height was measured annually (mean follow-up, 5.9 years) with a stadiometer.
Average height loss was 1.28 mm/yr among participants assigned to CaD, versus 1.26 mm/yr for women assigned to placebo (P=.35). A strong association (P<.001) was observed between age group and height loss. The study authors concluded that, compared with placebo, calcium and vitamin D supplementation used in this trial did not prevent height loss in healthy postmenopausal women.
Adequate calcium is necessary for bone health. While calcium supplementation may not be adequate to prevent fractures, it is also not involved in the inevitable loss of overall height seen in postmenopausal women. Calcium supplementation has been implicated in an increase in CVD. These data seem to indicate that, while calcium supplementation results in higher systolic blood pressure during the day, as well as higher coronary artery calcium scores, greater dietary calcium actually may decrease the incidence of atherosclerosis.
Sarcopenia: Still important, clinical approaches to easily detect it
Beaudart C, McCloskey E, Bruyére O, et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 2016;16(1):170.
In last year's update, I reviewed the article by He and colleagues11 on the relationship between sarcopenia and body composition with osteoporosis. Sarcopenia, which is the age-related loss of muscle mass and strength, is important to address in patients. Body composition and muscle strength are directly correlated with bone density, and this is not surprising since bone and muscle share some common hormonal, genetic, nutritional, and lifestyle determinants.12,13 Sarcopenia can be diagnosed via dual-energy x-ray absorptiometry (DXA) scan looking at lean muscle mass.
The term sarcopenia was first coined by Rosenberg and colleagues in 198914 as a progressive loss of skeletal muscle mass with advancing age. Since then, the definition has expanded to incorporate the notion of impaired muscle strength or physical performance. Sarcopenia is associated with morbidity and mortality from linked physical disability, falls, fractures, poor quality of life, depression, and hospitalization.15
Current research is focusing on nutritional exercise/activity-based and other novel interventions for improving the quality and quantity of skeletal muscle in older people. Some studies demonstrated that resistance training combined with nutritional supplements can improve muscle function.16
Details of the study
Beaudart and colleagues propose some user-friendly and inexpensive methods that can be utilized to assess sarcopenia in real life settings. They acknowledge that in research settings or even specialist clinical settings, DXA or computed tomography (CT) scans are the best assessment of muscle mass.
Anthropometric measurements. In a primary care setting, anthropometric measurement, especially calf circumference and mid-upper arm muscle circumference, correlate with overall muscle mass and reflect both health and nutritional status and predict performance, health, and survival in older people.
However, with advancing age, changes in the distribution of fat and loss of skin elasticity are such that circumference incurs a loss of accuracy and precision in older people. Some studies suggest that an adjustment of anthropometric measurements for age, sex, or BMI results in a better correlation with DXA-measured lean mass.17 Anthropometric measurements are simple clinical prediction tools that can be easily applied for sarcopenia since they offer the most portable, commonly applicable, inexpensive, and noninvasive technique for assessing size, proportions, and composition of the human body. However, their validity is limited when applied to individuals because cutoff points to identify low muscle mass still need to be defined. Still, serial measurements in a patient over time may be valuable.
Related article:
2014 Update on osteoporosis
Handgrip strength, as measured with a dynamometer, appears to be the most widely used method for the measurement of muscle strength. In general, isometric handgrip strength shows a good correlation with leg strength and also with lower extremity power, and calf cross-sectional muscle area. The measurement is easy to perform, inexpensive and does not require a specialist-trained staff.
Standardized conditions for the test include seating the patient in a standard chair with her forearms resting flat on the chair arms. Clinicians should demonstrate the use of the dynamometer and show that gripping very tightly registers the best score. Six measurements should be taken, 3 with each arm. Ideally, patients should be encouraged to squeeze as hard and tightly as possible during 3 to 5 seconds for each of the 6 trials; usually the highest reading of the 6 measurements is reported as the final result. The Jamar dynamometer, or similar hydraulic dynamometer, is the gold standard for this measurement.
Gait speed measurement. The most widely used tool in clinical practice for the assessment of physical performance is the gait speed measurement. The test is highly acceptable for participants and health professionals in clinical settings. No special equipment is required; it needs only a flat floor devoid of obstacles. In the 4-meter gait speed test, men and women with a gait speed of less than 0.8 meters/sec are described as having a poor physical performance. The average extra time added to the consultation by measuring the 4-meter gait speed was only 95 seconds (SD, 20 seconds).
Loss of muscle mass correlates with loss of bone mass as our patients age. In addition, such sarcopenia increases the risk of falls, a significant component of the rising rate of fragility fractures. Anthropometric measures, grip strength, and gait speed are easy, low-cost measures that can identify patients at increased risk.
Romosozumab: An interesting new agent to look forward to
Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532-1543.
Romosozumab is a monoclonal antibody that binds sclerostin, increasing bone formation and decreasing bone resorption. Cosman and colleagues enrolled 7,180 postmenopausal women with a T score of -2.5 to -3.5 at the total hip or femoral neck. Participants were randomly assigned to receive subcutaneous injections of romosozumab 210 mg or placebo monthly for 12 months. Thereafter, women in each group received subcutaneous denosumab 60 mg for 12 months--administered every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 and 24 months. Secondary end points included clinical and nonvertebral fractures.
Details of the study
At 12 months, new vertebral fractures had occurred in 16 of 3,321 women (0.5%) in the romosozumab group, as compared with 59 of 3,322 (1.8%) in the placebo group (representing a 73% lower risk of fracture with romosozumab; P<.001). Clinical fractures had occurred in 58 of 3,589 women (1.6%) in the romosozumab group, as compared with 90 of 3,591 (2.5%) in the placebo group (a 36% lower fracture risk with romosozumab; P = .008). Nonvertebral fractures had occurred in 56 of 3,589 women (1.6%) in the romosozumab group and in 75 of 3,591 (2.1%) in the placebo group (P = .10).
At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3,325 women] in the romosozumab group vs 2.5% [84 of 3,327 women] in the placebo group, a 75% lower risk with romosozumab; P<.001). Adverse events, including cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and 2 cases of osteonecrosis of the jaw were observed in the romosozumab group.
Lower risk of fracture
Thus, in postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year.
Of note, the effect of romosozumab on the risk of vertebral fracture was rapid, with only 2 additional vertebral fractures (of a total of 16 such fractures in the romosozumab group) occurring in the second 6 months of the first year of therapy. Because vertebral and clinical fractures are associated with increased morbidity and considerable health care costs, a treatment that would reduce this risk rapidly could offer appropriate patients an important benefit.
Romosozumab is a new agent. Though not yet available, it is extremely interesting because it not only decreases bone resorption but also increases bone formation. The results of this large prospective trial show that such an agent reduces both vertebral and clinical fracture and reduces that fracture risk quite rapidly within the first 6 months of therapy.
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- MacLaughlin KL, Faubion SS, Long ME, Pruthi S, Casey PM. Should the annual pelvic examination go the way of annual cervical cytology? Womens Health (Lond). 2014;10(4):373–384.
- Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520–2526.
- Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King AB, Tosterson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 2007;22(3):465–475.
- Kaunitz AM. Hormonal contraception in women of older reproductive age. N Engl J Med. 2008;358:1262–1270.
- Kaunitz AM. Oral contraceptive use in perimenopause. Am J Obstet Gynecol. 2001;185(2 suppl):S32–S37.
- Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54(2):176–180.
- Bailey R, Dodd K, Goldman J, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140(4):817–822.
- Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013;4(5):199–210.
- Moyer VA; U.S. Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158(9):691–696.
- Bristow SM, Gamble GD, Stewart A, Horne AM, Reid IR. Acute effects of calcium supplements on blood pressure and blood coagulation: secondary analysis of a randomised controlled trial in post-menopausal women. Br J Nutr. 2015;114(11):1868–1874.
- He H, Liu Y, Tian Q, Papasian CJ, Hu T, Deng HW. Relationship of sarcopenia and body composition with osteoporosis. Osteoporos Int. 2016;27(2):473–482.
- Coin A, Perissinotto E, Enzi G, et al. Predictors of low bone mineral density in the elderly: the role of dietary intake, nutritional status and sarcopenia. Eur J Clin Nutr. 2008;62(6):802–809.
- Taaffe DR, Cauley JA, Danielson M, et al. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study. J Bone Miner Res. 2001;16(7):1343–1352.
- Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 suppl):990S–991S.
- Beaudart C, Rizzoli R, Bruyere O, Reginster JY, Biver E. Sarcopenia: Burden and challenges for Public Health. Arch Public Health. 2014;72(1):45.
- Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–759.
- Kulkarni B, Kuper H, Taylor A, et al. Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women. J Appl Physiol. 2013;115(8):1156–1162.
- MacLaughlin KL, Faubion SS, Long ME, Pruthi S, Casey PM. Should the annual pelvic examination go the way of annual cervical cytology? Womens Health (Lond). 2014;10(4):373–384.
- Wright NC, Looker AC, Saag KG, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. 2014;29(11):2520–2526.
- Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King AB, Tosterson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 2007;22(3):465–475.
- Kaunitz AM. Hormonal contraception in women of older reproductive age. N Engl J Med. 2008;358:1262–1270.
- Kaunitz AM. Oral contraceptive use in perimenopause. Am J Obstet Gynecol. 2001;185(2 suppl):S32–S37.
- Gambacciani M, Cappagli B, Lazzarini V, Ciaponi M, Fruzzetti F, Genazzani AR. Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density. Maturitas. 2006;54(2):176–180.
- Bailey R, Dodd K, Goldman J, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140(4):817–822.
- Bolland MJ, Grey A, Reid IR. Calcium supplements and cardiovascular risk: 5 years on. Ther Adv Drug Saf. 2013;4(5):199–210.
- Moyer VA; U.S. Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;158(9):691–696.
- Bristow SM, Gamble GD, Stewart A, Horne AM, Reid IR. Acute effects of calcium supplements on blood pressure and blood coagulation: secondary analysis of a randomised controlled trial in post-menopausal women. Br J Nutr. 2015;114(11):1868–1874.
- He H, Liu Y, Tian Q, Papasian CJ, Hu T, Deng HW. Relationship of sarcopenia and body composition with osteoporosis. Osteoporos Int. 2016;27(2):473–482.
- Coin A, Perissinotto E, Enzi G, et al. Predictors of low bone mineral density in the elderly: the role of dietary intake, nutritional status and sarcopenia. Eur J Clin Nutr. 2008;62(6):802–809.
- Taaffe DR, Cauley JA, Danielson M, et al. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study. J Bone Miner Res. 2001;16(7):1343–1352.
- Rosenberg IH. Sarcopenia: origins and clinical relevance. J Nutr. 1997;127(5 suppl):990S–991S.
- Beaudart C, Rizzoli R, Bruyere O, Reginster JY, Biver E. Sarcopenia: Burden and challenges for Public Health. Arch Public Health. 2014;72(1):45.
- Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–759.
- Kulkarni B, Kuper H, Taylor A, et al. Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women. J Appl Physiol. 2013;115(8):1156–1162.
Mycophenolate puts lupus patients in remission faster than azathioprine
WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD, reported at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint of the trial was complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.
[email protected]
On Twitter @alz_gal
WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD, reported at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint of the trial was complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.
[email protected]
On Twitter @alz_gal
WASHINGTON – Mycophenolate sodium conferred complete remission sooner and more often than did azathioprine in a 24-month, open-label, randomized trial of patients with nonrenal systemic lupus erythematosus.
The enteric-coated version of mycophenolate used in the study was well tolerated, too, with just 7.5% of patients reporting gastrointestinal symptoms – a distinct advantage, Josefina Cortés-Hernández, MD, reported at the annual meeting of the American College of Rheumatology.
But azathioprine still holds one critical advantage over mycophenolate, said Dr. Cortés-Hernández of Vall d´Hebron Hospital, Barcelona: It is safe for use in pregnancy. “This is a very important advantage that we should not lose sight of,” she said.
Dr. Cortés-Hernández and her associates at 13 centers across Spain randomized 240 patients with nonrenal, active systemic lupus erythematosus (SLE) to either azathioprine (target dose, 2 mg/kg per day) or the enteric-coated mycophenolate sodium (target dose, 1,440 mg/day). Patients could add both a corticosteroid and an antimalarial as needed. No patient was allowed to take immunosuppressive therapy for at least 3 months before randomization.
The primary endpoint of the trial was complete remission at 3 months and 24 months, defined as an SLE Disease Activity Index (SLEDAI) less than 4 and/or absence of any BILAG (British Isles Lupus Assessment Group) A or B flares. Secondary endpoints were time to remission, time to first flare, and changes in prednisone use.
The patients were primarily women with a mean age of 41 years and mean disease duration of 5 years. The mean SLEDAI was 9.5; 45% had a mean SLEDAI of 10 or higher. The mean BILAG score was about 19. All the patients had autoantibodies, and about half had anti–double-stranded DNA antibodies. Half of the patients also had low complement C3 and/or C4 levels. About 80% were taking an antimalarial and 95%, a corticosteroid; the mean daily prednisone dose equivalent was about 19 mg.
In an intent-to-treat analysis, patients treated with mycophenolate had a higher remission rate at both 3 and 24 months. At 3 months, the complete remission rate was 33% for mycophenolate, compared with 19% for azathioprine. Clinical response improved over time in both groups, but mycophenolate remained significantly more effective over the entire study period. By 24 months, complete remission was present in 71% of those taking mycophenolate versus 48% of those taking azathioprine.
Both groups had significant improvements over baseline in both the SLEDAI and BILAG scores. By 24 months, the SLEDAI had dropped to a mean of 3 in the mycophenolate group and 4 in the azathioprine group. The BILAG dropped from a mean of 19 at baseline to 2 in the mycophenolate group and 5 in the azathioprine group.
BILAG A/B flares occurred in 50% of the mycophenolate group and 72% of the azathioprine group. The time to first flare was longer with mycophenolate, as was the time to a severe flare. New BILAG A flares occurred in 8% of the mycophenolate group and 22% of the azathioprine group. Azathioprine was associated with more renal flares (7% vs. 2%) and more hematologic flares (7.5% vs. 2.5%)
Steroid use declined to a prednisone equivalent of less than 7.5 mg/day in significantly more patients taking mycophenolate than azathioprine (95% vs. 85%).
Adverse events occurred in about 70% of each group; these were serious in about 10% of each group. Three patients taking mycophenolate and 10 taking azathioprine discontinued because of an adverse event, but this wasn’t statistically significant. Infections were the most common problem, occurring in about a quarter of each group; these were serious in five mycophenolate patients and seven azathioprine patients. There were two deaths, one in each group. Cancers occurred in three taking azathioprine and one taking mycophenolate. Leukopenia occurred in five patients taking azathioprine but in no one taking mycophenolate.
The study was funded by the Spanish Ministry of Health. Dr. Cortés-Hernández had no relevant financial disclosures.
[email protected]
On Twitter @alz_gal
Key clinical point:
Major finding: Complete remission rates at 3 months were 32% for mycophenolate and 19% for azathioprine.
Data source: A 24-month, open-label, randomized trial of 240 patients.
Disclosures: The Spanish Ministry of Health funded the study. Dr. Cortés-Hernández had no relevant financial disclosures.
Limited-Incision Knotless Achilles Tendon Repair
The incidence of midsubstance Achilles tendon ruptures is increasing in patients 30 years to 50 years of age, and more than 50% of these injuries occur during recreational basketball.1,2 Achilles ruptures occur more in deconditioned individuals engaged in explosive push-off and jumping activities. Management of these injuries has been controversial over the past decade; there is no consensus on nonoperative treatment, surgical repair, or optimal repair technique.1,3-7 According to American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines, limited-incision approaches have fewer overall complications relative to traditional open repair.3,4
Modern repair techniques, such as the Percutaneous Achilles Repair System (PARS; Arthrex), combine limited soft-tissue dissection with percutaneous suture insertion and knot tying.1,8 This limited-incision technique, employed since 2010, uses a 2-cm transverse incision and nondisposable metal jig with divergent needle passes and locking suture fixation options to secure and fix both tendon ends with minimal dissection of skin, subcutaneous tissue, and paratenon. A review of 270 surgically treated Achilles tendon ruptures (101 PARS, 169 traditional open repair) found that, compared with the open repair group, the PARS group had significantly shorter operative times and more patients returning to baseline physical activities within 5 months after surgery.1 Although the difference was not statistically significant, the overall postoperative complication rate was 5% for the PARS group and 11% for the open repair group. The PARS group had no cases of sural neuritis or deep infection requiring reoperation.
Although the PARS technique has had good outcomes with few complications, care must be taken during surgery to prevent sutures from pulling through the tendon near the rupture site, which can result from overtensioning and from suture knot irritation against superficial soft tissues. Given these potential issues, the PARS procedure was modified (Achilles Midsubstance SpeedBridge; Arthrex) to provide knotless restoration of musculotendinous length in a reliable, reproducible fashion and direct fixation of tendon to bone for early mobilization.9 This new procedure bypasses suture fixation in the compromised tendon ends adjacent to the rupture site, thereby reducing suture slippage and allowing for potential early range of motion and weight-bearing relative to previous techniques. Preliminary results from a cohort of 34 patients treated with this technique are promising: Average return to baseline activities was 18.2 weeks (range, 9-26 weeks), and there were no wound complications, nerve injuries, or reruptures.9Indications are overall health and an acute midsubstance Achilles rupture that presents within 3 weeks after injury (the time limit is used to ensure that both tendon ends can be mobilized and repaired to appropriate length). A relative contraindication is delayed presentation (≥4 weeks), which may require open reconstruction in combination with V-Y lengthening or other adjuvant procedures. Other relative contraindications are insertional rupture, Achilles tendinopathy, and a significant medical comorbidity that prohibits surgical intervention.
Surgical Technique
Operating Room Setup and Approach
The patient is positioned prone with chest rolls and kneepads and with arms at <90° of abduction (Figures 1A-1E). 
A “no-touch” technique is used without pickups, and soft tissues are carefully dissected with small scissors down to the paratenon. The sural nerve typically is not visible in the operative field, but, if it is, it can be dissected out and retracted out of the way. A transverse incision is made through the paratenon, and expression of rupture hematoma often follows. Paratenon preservation is key in minimizing disruption of the native vascular supply of the tendon and allowing for repair at the end of the case. A freer can be placed within the wound to confirm that the center of the rupture has been identified.
An Allis clamp is inserted into the wound, and the proximal tendon stump is secured and then pulled about 1 cm through the wound. A freer is circumferentially run along the sides of the proximal tendon to release any potential adhesions that may limit distal excursion.
PARS Jig Insertion and Suture Passing
The PARS jig is inserted into the wound with the inner prongs in the narrowest position possible. The curved jig is inserted proximally, and the center turn wheel is used to widen the inner prongs so they can slide along the sides of the tendon in the paratenon. Proper jig placement should be smooth and encounter little resistance. The proximal tendon is in a superficial location and can be palpated within the prongs of the jig to double-check that the tendon is centered within the jig. A frequent error is to insert the jig too deep, which subsequently causes needles and sutures to miss the tendon and pull through.
Keeping the jig centralized in neutral rotation minimizes improper suture passing and avoids iatrogenic injury to the medial and lateral neurovascular structures. During suture passing, all needles (1.6 mm) with nitinol loops are first used unloaded without suture. The first 2 needles are inserted into their respective, numbered holes, through the tendon, and then through the opposite side of the jig. Each needle is checked to make sure that it does not pass outside the jig. Having 2 needles within the jig and tendon at all times during suture passing helps stabilize the jig and avoids adjacent suture piercing with the subsequent needle.
A No. 2 FiberWire suture (Arthrex) is then passed through the first hole using the needle suture passer and made even in length on both sides. The specific colors of the suture are not important, but the order of the sutures placed is. An assistant can write down the colors and order of the sutures passed. Before the second suture is passed, the first needle is inserted back through the jig and tendon into the third hole. The third and fourth sutures (green-striped) differ from the other sutures in that one end has a loop and the other has a tail, and they are passed in an oblique, crossing pattern. These sutures later help create a locking suture on either side of the tendon.
After these sutures are passed, the final result should be 1 green-striped loop and 1 green-striped tail on either side of the tendon. The fifth suture is passed straight across the tendon in a trajectory similar to that of the first suture. In large laborers, obese patients, and elite athletes, 2 additional green-striped sutures can be passed through the optional sixth and seventh holes to create an additional locking suture.
PARS Jig Removal and Suture Management
After all sutures are passed, the turn wheel is used to narrow the inner prongs while gentle, controlled tension is applied to the jig to remove it from the wound (Figures 2A-2C). 
Pullout of any suture from the tendon indicates that the tendon was not centered in the jig or was not proximal enough along the tendon during suture passing. If a suture pulls out, it is removed, and the previous steps are repeated with close attention paid to tendon positioning within the jig. It is not advised to extend the incision longitudinally on either end of the transverse incision, as doing so can lead to potential wound-healing complications. After proximal fixation is achieved, all sutures on each side of the tendon are neatly spread apart in the following order from proximal to distal: first suture, second suture, looped green-striped (third) suture, tail green-striped (fourth) suture, fifth suture. The second suture on both sides is then looped around the 2 green-striped sutures and back proximally through the looped end of the green-striped suture.
The green-striped suture tail is pulled through the tendon to the opposite side to create a locking suture on both sides of the tendon. In the end, there are 2 nonlocking sutures and 1 locking suture on either side of the tendon. Each pair of sutures is pulled distally to confirm fixation and remove any initial suture creep from the system. A hemostat is placed on each group of 3 sutures to keep them out of the way during distal anchor preparation.
Distal Anchor Preparation and Banana SutureLasso Passing
Two longitudinal 5-mm incisions are made along the posterior aspect of the heel just distal to the area of maximal heel convexity. Incisions are spaced 1.5 cm apart along the sides of the Achilles tendon insertion. A 3.5-mm drill and a drill guide are used through each incision and placed flush against bone (Figures 3A-3E). 
A Banana SutureLasso (Arthrex) with inner nitinol wire is passed through the center of the distal Achilles tendon stump and out the proximal incision to retrieve one side of the proximal sutures. SutureLasso passage through tendon can be facilitated with tactile feedback. The surgeon’s nondominant thumb is placed directly against the distal tendon while the dominant hand grasps the SutureLasso with the thumb near the tip. As the SutureLasso is advanced proximally through the tendon, the surgeon can feel its tip meeting mild resistance. Confirm that the tip of the SutureLasso is in the center of the distal tendon by direct visual inspection through the wound.
The inner nitinol wire is advanced 2 cm to 3 cm out of the tip of the SutureLasso, and sutures are passed through the distal Achilles tendon. During suture passing, the nitinol wire is drawn back to the tip of the SutureLasso, and then the entire SutureLasso is removed from the distal incision. Trying to pass the sutures only through the inner nitinol wire can result in suture tangling and increased resistance. The process is then repeated for the sutures on the opposite side. Suture pairs are placed under maximal tension and cycled multiple times (5-10) to remove any residual proximal suture creep.10
Achilles Tensioning and Anchor Insertion
The ankle is plantar flexed to tension the Achilles tendon relative to the contralateral limb and is held in place by an assistant (Figures 4A-4E). 
Position of the drill holes can be rechecked with a Kirschner wire before anchor insertion, as their relative position changes with ankle plantar flexion. It is not necessary to premeasure and adjust suture length at the tip of the anchor as in other blind tunnel anchor insertion techniques (eg, InternalBrace; Arthrex). Once the anchor tip is malleted into bone, the free suture ends are released to avoid overtensioning the tendon. Before the anchor insertion handle is completely removed, the tip of a mosquito clamp can be used to feel the bony surface and confirm the anchor is completely seated.
With the ankle still held in the appropriate amount of plantarflexion, the process is repeated and the other SwiveLock anchor inserted. Sutures are cut flush with the anchor, and the surgeon performs wound irrigation and layered closure, with absorbable suture, of the paratenon and subcutaneous tissues. After skin closure with nylon suture, resting ankle plantarflexion is assessed and the Thompson test performed. The patient is placed in a well-padded non-weight-bearing plantar flexion splint for incision and initial tendon healing during the first 2 weeks after surgery.
Discussion
A key aspect of recovery is the balance achieved between skin and tendon healing and early mobilization, as outcomes of surgical repair of Achilles ruptures are improved with early weight-bearing and functional rehabilitation.11-13 Some surgeons recommend weight-bearing immediately after surgery, given the direct tendon-to-bone fixation achieved with repair.9 I prefer 2 weeks of non-weight-bearing, which allows the skin to heal adequately and the initial soft-tissue inflammation to subside. If the incision is healed at 2 weeks, sutures are removed, and the patient is transitioned to a tall, non-weight-bearing CAM (controlled ankle motion) boot, worn for 1 to 2 weeks with initiation of gentle ankle range-of-motion exercises. If there is any concern about wound healing, sutures are maintained for another 1 to 2 weeks.
Between 3 and 8 weeks after surgery, progressive weight-bearing is initiated with a peel-away heel lift (~2 cm thick total, 3 layers). Each lift layer is removed as pain allows, every 2 to 3 days. The goal is full weight-bearing with the foot flat 5 to 6 weeks after surgery. Physical therapy focusing on ankle motion and gentle Achilles stretching and strengthening is started 5 to 6 weeks after surgery, depending on progression and functional needs. Between 8 and 12 weeks after surgery, the patient is transitioned to normal shoe wear with increased activities. Running and jumping are allowed, as pain and swelling allow, starting at 12 weeks.
Although preliminary outcomes and experience with the Achilles Midsubstance SpeedBridge have been favorable, long-term clinical and functional studies are needed to determine the specific advantages and disadvantages of this new technique relative to other repairs. The main benefits observed thus far are reduced subjective knot tying and tensioning, decreased reliance on suture fixation in compromised tissue at the rupture site, reduced risk of FiberWire knot irritation of superficial soft tissues, lower risk of distal suture pullout, and earlier mobilization owing to bony fixation of the tendon. Potential complications include anchor-site heel pain caused by prominent anchors or by the bone edema that occurs when a patient increases physical activity by a significant amount at 12 weeks.9 Heel pain caused by bone edema resolves by 20 weeks without intervention.
Stress shielding of the distal Achilles tendon is a theoretical concern given the tendon–bone construct, but there have been no reports of tendon atrophy or repair failure caused by stress shielding. The original PARS technique was often used to create Achilles tension with the ankle maximally plantar flexed—the idea being that the tendon would gradually stretch over time.1 Overtensioning the Achilles repair is a potential complication with the SpeedBridge, as the distal anchors provide a more rigid point of distal fixation. Surgeons can avoid this complication by cycling the sutures to remove any residual creep and then tensioning the Achilles according to the contralateral limb and/or palpating tendon opposition at the rupture site.
Overall, this new limited-incision knotless Achilles tendon repair technique allows for minimal soft-tissue dissection, restoration of Achilles musculotendinous length, and direct tendon-to-bone fixation. Early results are promising, but long-term clinical outcomes and comparative analysis are needed. In addition, many details of this technique must be clarified—including incidence of short- and long-term complications in larger cohorts, optimal suture material and configuration, and risks and benefits of immediate (<2 weeks) and delayed (2-4 weeks) weight-bearing.
Am J Orthop. 2016;45(7):E487-E492. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Hsu AR, Jones CP, Cohen BE, Davis WH, Ellington JK, Anderson RB. Clinical outcomes and complications of Percutaneous Achilles Repair System versus open technique for acute Achilles tendon ruptures. Foot Ankle Int. 2015;36(11):1279-1286.
2. Raikin SM, Garras DN, Krapchev PV. Achilles tendon injuries in a United States population. Foot Ankle Int. 2013;34(4):475-480.
3. Chiodo CP, Glazebrook M, Bluman EM, et al; American Academy of Orthopaedic Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on treatment of Achilles tendon rupture. J Bone Joint Surg Am. 2010;92(14):2466-2468.
4. Chiodo CP, Glazebrook M, Bluman EM, et al; American Academy of Orthopaedic Surgeons. Diagnosis and treatment of acute Achilles tendon rupture. J Am Acad Orthop Surg. 2010;18(8):503-510.
5. Khan RJ, Fick D, Keogh A, Crawford J, Brammar T, Parker M. Treatment of acute Achilles tendon ruptures. A meta-analysis of randomized, controlled trials. J Bone Joint Surg Am. 2005;87(10):2202-2210.
6. Renninger CH, Kuhn K, Fellars T, Youngblood S, Bellamy J. Operative and nonoperative management of Achilles tendon ruptures in active duty military population. Foot Ankle Int. 2016;37(3):269-273.
7. Khan RJ, Carey Smith RL. Surgical interventions for treating acute Achilles tendon ruptures. Cochrane Database Syst Rev. 2010;(9):CD003674.
8. McCullough KA, Shaw CM, Anderson RB. Mini-open repair of Achilles rupture in the National Football League. J Surg Orthop Adv. 2014;23(4):179-183.
9. McWilliam JR, Mackay G. The internal brace for midsubstance Achilles ruptures. Foot Ankle Int. 2016;37(7):794-800.
10. Clanton TO, Haytmanek CT, Williams BT, et al. A biomechanical comparison of an open repair and 3 minimally invasive percutaneous Achilles tendon repair techniques during a simulated, progressive rehabilitation protocol. Am J Sports Med. 2015;43(8):1957-1964.
11. Aoki M, Ogiwara N, Ohta T, Nabeta Y. Early active motion and weightbearing after cross-stitch Achilles tendon repair. Am J Sports Med. 1998;26(6):794-800.
12. Kangas J, Pajala A, Ohtonen P, Leppilahti J. Achilles tendon elongation after rupture repair: a randomized comparison of 2 postoperative regimens. Am J Sports Med. 2007;35(1):59-64.
13. Kangas J, Pajala A, Siira P, Hämäläinen M, Leppilahti J. Early functional treatment versus early immobilization in tension of the musculotendinous unit after Achilles rupture repair: a prospective, randomized, clinical study. J Trauma. 2003;54(6):1171-1180.
The incidence of midsubstance Achilles tendon ruptures is increasing in patients 30 years to 50 years of age, and more than 50% of these injuries occur during recreational basketball.1,2 Achilles ruptures occur more in deconditioned individuals engaged in explosive push-off and jumping activities. Management of these injuries has been controversial over the past decade; there is no consensus on nonoperative treatment, surgical repair, or optimal repair technique.1,3-7 According to American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines, limited-incision approaches have fewer overall complications relative to traditional open repair.3,4
Modern repair techniques, such as the Percutaneous Achilles Repair System (PARS; Arthrex), combine limited soft-tissue dissection with percutaneous suture insertion and knot tying.1,8 This limited-incision technique, employed since 2010, uses a 2-cm transverse incision and nondisposable metal jig with divergent needle passes and locking suture fixation options to secure and fix both tendon ends with minimal dissection of skin, subcutaneous tissue, and paratenon. A review of 270 surgically treated Achilles tendon ruptures (101 PARS, 169 traditional open repair) found that, compared with the open repair group, the PARS group had significantly shorter operative times and more patients returning to baseline physical activities within 5 months after surgery.1 Although the difference was not statistically significant, the overall postoperative complication rate was 5% for the PARS group and 11% for the open repair group. The PARS group had no cases of sural neuritis or deep infection requiring reoperation.
Although the PARS technique has had good outcomes with few complications, care must be taken during surgery to prevent sutures from pulling through the tendon near the rupture site, which can result from overtensioning and from suture knot irritation against superficial soft tissues. Given these potential issues, the PARS procedure was modified (Achilles Midsubstance SpeedBridge; Arthrex) to provide knotless restoration of musculotendinous length in a reliable, reproducible fashion and direct fixation of tendon to bone for early mobilization.9 This new procedure bypasses suture fixation in the compromised tendon ends adjacent to the rupture site, thereby reducing suture slippage and allowing for potential early range of motion and weight-bearing relative to previous techniques. Preliminary results from a cohort of 34 patients treated with this technique are promising: Average return to baseline activities was 18.2 weeks (range, 9-26 weeks), and there were no wound complications, nerve injuries, or reruptures.9Indications are overall health and an acute midsubstance Achilles rupture that presents within 3 weeks after injury (the time limit is used to ensure that both tendon ends can be mobilized and repaired to appropriate length). A relative contraindication is delayed presentation (≥4 weeks), which may require open reconstruction in combination with V-Y lengthening or other adjuvant procedures. Other relative contraindications are insertional rupture, Achilles tendinopathy, and a significant medical comorbidity that prohibits surgical intervention.
Surgical Technique
Operating Room Setup and Approach
The patient is positioned prone with chest rolls and kneepads and with arms at <90° of abduction (Figures 1A-1E).
A “no-touch” technique is used without pickups, and soft tissues are carefully dissected with small scissors down to the paratenon. The sural nerve typically is not visible in the operative field, but, if it is, it can be dissected out and retracted out of the way. A transverse incision is made through the paratenon, and expression of rupture hematoma often follows. Paratenon preservation is key in minimizing disruption of the native vascular supply of the tendon and allowing for repair at the end of the case. A freer can be placed within the wound to confirm that the center of the rupture has been identified.
An Allis clamp is inserted into the wound, and the proximal tendon stump is secured and then pulled about 1 cm through the wound. A freer is circumferentially run along the sides of the proximal tendon to release any potential adhesions that may limit distal excursion.
PARS Jig Insertion and Suture Passing
The PARS jig is inserted into the wound with the inner prongs in the narrowest position possible. The curved jig is inserted proximally, and the center turn wheel is used to widen the inner prongs so they can slide along the sides of the tendon in the paratenon. Proper jig placement should be smooth and encounter little resistance. The proximal tendon is in a superficial location and can be palpated within the prongs of the jig to double-check that the tendon is centered within the jig. A frequent error is to insert the jig too deep, which subsequently causes needles and sutures to miss the tendon and pull through.
Keeping the jig centralized in neutral rotation minimizes improper suture passing and avoids iatrogenic injury to the medial and lateral neurovascular structures. During suture passing, all needles (1.6 mm) with nitinol loops are first used unloaded without suture. The first 2 needles are inserted into their respective, numbered holes, through the tendon, and then through the opposite side of the jig. Each needle is checked to make sure that it does not pass outside the jig. Having 2 needles within the jig and tendon at all times during suture passing helps stabilize the jig and avoids adjacent suture piercing with the subsequent needle.
A No. 2 FiberWire suture (Arthrex) is then passed through the first hole using the needle suture passer and made even in length on both sides. The specific colors of the suture are not important, but the order of the sutures placed is. An assistant can write down the colors and order of the sutures passed. Before the second suture is passed, the first needle is inserted back through the jig and tendon into the third hole. The third and fourth sutures (green-striped) differ from the other sutures in that one end has a loop and the other has a tail, and they are passed in an oblique, crossing pattern. These sutures later help create a locking suture on either side of the tendon.
After these sutures are passed, the final result should be 1 green-striped loop and 1 green-striped tail on either side of the tendon. The fifth suture is passed straight across the tendon in a trajectory similar to that of the first suture. In large laborers, obese patients, and elite athletes, 2 additional green-striped sutures can be passed through the optional sixth and seventh holes to create an additional locking suture.
PARS Jig Removal and Suture Management
After all sutures are passed, the turn wheel is used to narrow the inner prongs while gentle, controlled tension is applied to the jig to remove it from the wound (Figures 2A-2C).
Pullout of any suture from the tendon indicates that the tendon was not centered in the jig or was not proximal enough along the tendon during suture passing. If a suture pulls out, it is removed, and the previous steps are repeated with close attention paid to tendon positioning within the jig. It is not advised to extend the incision longitudinally on either end of the transverse incision, as doing so can lead to potential wound-healing complications. After proximal fixation is achieved, all sutures on each side of the tendon are neatly spread apart in the following order from proximal to distal: first suture, second suture, looped green-striped (third) suture, tail green-striped (fourth) suture, fifth suture. The second suture on both sides is then looped around the 2 green-striped sutures and back proximally through the looped end of the green-striped suture.
The green-striped suture tail is pulled through the tendon to the opposite side to create a locking suture on both sides of the tendon. In the end, there are 2 nonlocking sutures and 1 locking suture on either side of the tendon. Each pair of sutures is pulled distally to confirm fixation and remove any initial suture creep from the system. A hemostat is placed on each group of 3 sutures to keep them out of the way during distal anchor preparation.
Distal Anchor Preparation and Banana SutureLasso Passing
Two longitudinal 5-mm incisions are made along the posterior aspect of the heel just distal to the area of maximal heel convexity. Incisions are spaced 1.5 cm apart along the sides of the Achilles tendon insertion. A 3.5-mm drill and a drill guide are used through each incision and placed flush against bone (Figures 3A-3E).
A Banana SutureLasso (Arthrex) with inner nitinol wire is passed through the center of the distal Achilles tendon stump and out the proximal incision to retrieve one side of the proximal sutures. SutureLasso passage through tendon can be facilitated with tactile feedback. The surgeon’s nondominant thumb is placed directly against the distal tendon while the dominant hand grasps the SutureLasso with the thumb near the tip. As the SutureLasso is advanced proximally through the tendon, the surgeon can feel its tip meeting mild resistance. Confirm that the tip of the SutureLasso is in the center of the distal tendon by direct visual inspection through the wound.
The inner nitinol wire is advanced 2 cm to 3 cm out of the tip of the SutureLasso, and sutures are passed through the distal Achilles tendon. During suture passing, the nitinol wire is drawn back to the tip of the SutureLasso, and then the entire SutureLasso is removed from the distal incision. Trying to pass the sutures only through the inner nitinol wire can result in suture tangling and increased resistance. The process is then repeated for the sutures on the opposite side. Suture pairs are placed under maximal tension and cycled multiple times (5-10) to remove any residual proximal suture creep.10
Achilles Tensioning and Anchor Insertion
The ankle is plantar flexed to tension the Achilles tendon relative to the contralateral limb and is held in place by an assistant (Figures 4A-4E).
Position of the drill holes can be rechecked with a Kirschner wire before anchor insertion, as their relative position changes with ankle plantar flexion. It is not necessary to premeasure and adjust suture length at the tip of the anchor as in other blind tunnel anchor insertion techniques (eg, InternalBrace; Arthrex). Once the anchor tip is malleted into bone, the free suture ends are released to avoid overtensioning the tendon. Before the anchor insertion handle is completely removed, the tip of a mosquito clamp can be used to feel the bony surface and confirm the anchor is completely seated.
With the ankle still held in the appropriate amount of plantarflexion, the process is repeated and the other SwiveLock anchor inserted. Sutures are cut flush with the anchor, and the surgeon performs wound irrigation and layered closure, with absorbable suture, of the paratenon and subcutaneous tissues. After skin closure with nylon suture, resting ankle plantarflexion is assessed and the Thompson test performed. The patient is placed in a well-padded non-weight-bearing plantar flexion splint for incision and initial tendon healing during the first 2 weeks after surgery.
Discussion
A key aspect of recovery is the balance achieved between skin and tendon healing and early mobilization, as outcomes of surgical repair of Achilles ruptures are improved with early weight-bearing and functional rehabilitation.11-13 Some surgeons recommend weight-bearing immediately after surgery, given the direct tendon-to-bone fixation achieved with repair.9 I prefer 2 weeks of non-weight-bearing, which allows the skin to heal adequately and the initial soft-tissue inflammation to subside. If the incision is healed at 2 weeks, sutures are removed, and the patient is transitioned to a tall, non-weight-bearing CAM (controlled ankle motion) boot, worn for 1 to 2 weeks with initiation of gentle ankle range-of-motion exercises. If there is any concern about wound healing, sutures are maintained for another 1 to 2 weeks.
Between 3 and 8 weeks after surgery, progressive weight-bearing is initiated with a peel-away heel lift (~2 cm thick total, 3 layers). Each lift layer is removed as pain allows, every 2 to 3 days. The goal is full weight-bearing with the foot flat 5 to 6 weeks after surgery. Physical therapy focusing on ankle motion and gentle Achilles stretching and strengthening is started 5 to 6 weeks after surgery, depending on progression and functional needs. Between 8 and 12 weeks after surgery, the patient is transitioned to normal shoe wear with increased activities. Running and jumping are allowed, as pain and swelling allow, starting at 12 weeks.
Although preliminary outcomes and experience with the Achilles Midsubstance SpeedBridge have been favorable, long-term clinical and functional studies are needed to determine the specific advantages and disadvantages of this new technique relative to other repairs. The main benefits observed thus far are reduced subjective knot tying and tensioning, decreased reliance on suture fixation in compromised tissue at the rupture site, reduced risk of FiberWire knot irritation of superficial soft tissues, lower risk of distal suture pullout, and earlier mobilization owing to bony fixation of the tendon. Potential complications include anchor-site heel pain caused by prominent anchors or by the bone edema that occurs when a patient increases physical activity by a significant amount at 12 weeks.9 Heel pain caused by bone edema resolves by 20 weeks without intervention.
Stress shielding of the distal Achilles tendon is a theoretical concern given the tendon–bone construct, but there have been no reports of tendon atrophy or repair failure caused by stress shielding. The original PARS technique was often used to create Achilles tension with the ankle maximally plantar flexed—the idea being that the tendon would gradually stretch over time.1 Overtensioning the Achilles repair is a potential complication with the SpeedBridge, as the distal anchors provide a more rigid point of distal fixation. Surgeons can avoid this complication by cycling the sutures to remove any residual creep and then tensioning the Achilles according to the contralateral limb and/or palpating tendon opposition at the rupture site.
Overall, this new limited-incision knotless Achilles tendon repair technique allows for minimal soft-tissue dissection, restoration of Achilles musculotendinous length, and direct tendon-to-bone fixation. Early results are promising, but long-term clinical outcomes and comparative analysis are needed. In addition, many details of this technique must be clarified—including incidence of short- and long-term complications in larger cohorts, optimal suture material and configuration, and risks and benefits of immediate (<2 weeks) and delayed (2-4 weeks) weight-bearing.
Am J Orthop. 2016;45(7):E487-E492. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
The incidence of midsubstance Achilles tendon ruptures is increasing in patients 30 years to 50 years of age, and more than 50% of these injuries occur during recreational basketball.1,2 Achilles ruptures occur more in deconditioned individuals engaged in explosive push-off and jumping activities. Management of these injuries has been controversial over the past decade; there is no consensus on nonoperative treatment, surgical repair, or optimal repair technique.1,3-7 According to American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines, limited-incision approaches have fewer overall complications relative to traditional open repair.3,4
Modern repair techniques, such as the Percutaneous Achilles Repair System (PARS; Arthrex), combine limited soft-tissue dissection with percutaneous suture insertion and knot tying.1,8 This limited-incision technique, employed since 2010, uses a 2-cm transverse incision and nondisposable metal jig with divergent needle passes and locking suture fixation options to secure and fix both tendon ends with minimal dissection of skin, subcutaneous tissue, and paratenon. A review of 270 surgically treated Achilles tendon ruptures (101 PARS, 169 traditional open repair) found that, compared with the open repair group, the PARS group had significantly shorter operative times and more patients returning to baseline physical activities within 5 months after surgery.1 Although the difference was not statistically significant, the overall postoperative complication rate was 5% for the PARS group and 11% for the open repair group. The PARS group had no cases of sural neuritis or deep infection requiring reoperation.
Although the PARS technique has had good outcomes with few complications, care must be taken during surgery to prevent sutures from pulling through the tendon near the rupture site, which can result from overtensioning and from suture knot irritation against superficial soft tissues. Given these potential issues, the PARS procedure was modified (Achilles Midsubstance SpeedBridge; Arthrex) to provide knotless restoration of musculotendinous length in a reliable, reproducible fashion and direct fixation of tendon to bone for early mobilization.9 This new procedure bypasses suture fixation in the compromised tendon ends adjacent to the rupture site, thereby reducing suture slippage and allowing for potential early range of motion and weight-bearing relative to previous techniques. Preliminary results from a cohort of 34 patients treated with this technique are promising: Average return to baseline activities was 18.2 weeks (range, 9-26 weeks), and there were no wound complications, nerve injuries, or reruptures.9Indications are overall health and an acute midsubstance Achilles rupture that presents within 3 weeks after injury (the time limit is used to ensure that both tendon ends can be mobilized and repaired to appropriate length). A relative contraindication is delayed presentation (≥4 weeks), which may require open reconstruction in combination with V-Y lengthening or other adjuvant procedures. Other relative contraindications are insertional rupture, Achilles tendinopathy, and a significant medical comorbidity that prohibits surgical intervention.
Surgical Technique
Operating Room Setup and Approach
The patient is positioned prone with chest rolls and kneepads and with arms at <90° of abduction (Figures 1A-1E).
A “no-touch” technique is used without pickups, and soft tissues are carefully dissected with small scissors down to the paratenon. The sural nerve typically is not visible in the operative field, but, if it is, it can be dissected out and retracted out of the way. A transverse incision is made through the paratenon, and expression of rupture hematoma often follows. Paratenon preservation is key in minimizing disruption of the native vascular supply of the tendon and allowing for repair at the end of the case. A freer can be placed within the wound to confirm that the center of the rupture has been identified.
An Allis clamp is inserted into the wound, and the proximal tendon stump is secured and then pulled about 1 cm through the wound. A freer is circumferentially run along the sides of the proximal tendon to release any potential adhesions that may limit distal excursion.
PARS Jig Insertion and Suture Passing
The PARS jig is inserted into the wound with the inner prongs in the narrowest position possible. The curved jig is inserted proximally, and the center turn wheel is used to widen the inner prongs so they can slide along the sides of the tendon in the paratenon. Proper jig placement should be smooth and encounter little resistance. The proximal tendon is in a superficial location and can be palpated within the prongs of the jig to double-check that the tendon is centered within the jig. A frequent error is to insert the jig too deep, which subsequently causes needles and sutures to miss the tendon and pull through.
Keeping the jig centralized in neutral rotation minimizes improper suture passing and avoids iatrogenic injury to the medial and lateral neurovascular structures. During suture passing, all needles (1.6 mm) with nitinol loops are first used unloaded without suture. The first 2 needles are inserted into their respective, numbered holes, through the tendon, and then through the opposite side of the jig. Each needle is checked to make sure that it does not pass outside the jig. Having 2 needles within the jig and tendon at all times during suture passing helps stabilize the jig and avoids adjacent suture piercing with the subsequent needle.
A No. 2 FiberWire suture (Arthrex) is then passed through the first hole using the needle suture passer and made even in length on both sides. The specific colors of the suture are not important, but the order of the sutures placed is. An assistant can write down the colors and order of the sutures passed. Before the second suture is passed, the first needle is inserted back through the jig and tendon into the third hole. The third and fourth sutures (green-striped) differ from the other sutures in that one end has a loop and the other has a tail, and they are passed in an oblique, crossing pattern. These sutures later help create a locking suture on either side of the tendon.
After these sutures are passed, the final result should be 1 green-striped loop and 1 green-striped tail on either side of the tendon. The fifth suture is passed straight across the tendon in a trajectory similar to that of the first suture. In large laborers, obese patients, and elite athletes, 2 additional green-striped sutures can be passed through the optional sixth and seventh holes to create an additional locking suture.
PARS Jig Removal and Suture Management
After all sutures are passed, the turn wheel is used to narrow the inner prongs while gentle, controlled tension is applied to the jig to remove it from the wound (Figures 2A-2C).
Pullout of any suture from the tendon indicates that the tendon was not centered in the jig or was not proximal enough along the tendon during suture passing. If a suture pulls out, it is removed, and the previous steps are repeated with close attention paid to tendon positioning within the jig. It is not advised to extend the incision longitudinally on either end of the transverse incision, as doing so can lead to potential wound-healing complications. After proximal fixation is achieved, all sutures on each side of the tendon are neatly spread apart in the following order from proximal to distal: first suture, second suture, looped green-striped (third) suture, tail green-striped (fourth) suture, fifth suture. The second suture on both sides is then looped around the 2 green-striped sutures and back proximally through the looped end of the green-striped suture.
The green-striped suture tail is pulled through the tendon to the opposite side to create a locking suture on both sides of the tendon. In the end, there are 2 nonlocking sutures and 1 locking suture on either side of the tendon. Each pair of sutures is pulled distally to confirm fixation and remove any initial suture creep from the system. A hemostat is placed on each group of 3 sutures to keep them out of the way during distal anchor preparation.
Distal Anchor Preparation and Banana SutureLasso Passing
Two longitudinal 5-mm incisions are made along the posterior aspect of the heel just distal to the area of maximal heel convexity. Incisions are spaced 1.5 cm apart along the sides of the Achilles tendon insertion. A 3.5-mm drill and a drill guide are used through each incision and placed flush against bone (Figures 3A-3E).
A Banana SutureLasso (Arthrex) with inner nitinol wire is passed through the center of the distal Achilles tendon stump and out the proximal incision to retrieve one side of the proximal sutures. SutureLasso passage through tendon can be facilitated with tactile feedback. The surgeon’s nondominant thumb is placed directly against the distal tendon while the dominant hand grasps the SutureLasso with the thumb near the tip. As the SutureLasso is advanced proximally through the tendon, the surgeon can feel its tip meeting mild resistance. Confirm that the tip of the SutureLasso is in the center of the distal tendon by direct visual inspection through the wound.
The inner nitinol wire is advanced 2 cm to 3 cm out of the tip of the SutureLasso, and sutures are passed through the distal Achilles tendon. During suture passing, the nitinol wire is drawn back to the tip of the SutureLasso, and then the entire SutureLasso is removed from the distal incision. Trying to pass the sutures only through the inner nitinol wire can result in suture tangling and increased resistance. The process is then repeated for the sutures on the opposite side. Suture pairs are placed under maximal tension and cycled multiple times (5-10) to remove any residual proximal suture creep.10
Achilles Tensioning and Anchor Insertion
The ankle is plantar flexed to tension the Achilles tendon relative to the contralateral limb and is held in place by an assistant (Figures 4A-4E).
Position of the drill holes can be rechecked with a Kirschner wire before anchor insertion, as their relative position changes with ankle plantar flexion. It is not necessary to premeasure and adjust suture length at the tip of the anchor as in other blind tunnel anchor insertion techniques (eg, InternalBrace; Arthrex). Once the anchor tip is malleted into bone, the free suture ends are released to avoid overtensioning the tendon. Before the anchor insertion handle is completely removed, the tip of a mosquito clamp can be used to feel the bony surface and confirm the anchor is completely seated.
With the ankle still held in the appropriate amount of plantarflexion, the process is repeated and the other SwiveLock anchor inserted. Sutures are cut flush with the anchor, and the surgeon performs wound irrigation and layered closure, with absorbable suture, of the paratenon and subcutaneous tissues. After skin closure with nylon suture, resting ankle plantarflexion is assessed and the Thompson test performed. The patient is placed in a well-padded non-weight-bearing plantar flexion splint for incision and initial tendon healing during the first 2 weeks after surgery.
Discussion
A key aspect of recovery is the balance achieved between skin and tendon healing and early mobilization, as outcomes of surgical repair of Achilles ruptures are improved with early weight-bearing and functional rehabilitation.11-13 Some surgeons recommend weight-bearing immediately after surgery, given the direct tendon-to-bone fixation achieved with repair.9 I prefer 2 weeks of non-weight-bearing, which allows the skin to heal adequately and the initial soft-tissue inflammation to subside. If the incision is healed at 2 weeks, sutures are removed, and the patient is transitioned to a tall, non-weight-bearing CAM (controlled ankle motion) boot, worn for 1 to 2 weeks with initiation of gentle ankle range-of-motion exercises. If there is any concern about wound healing, sutures are maintained for another 1 to 2 weeks.
Between 3 and 8 weeks after surgery, progressive weight-bearing is initiated with a peel-away heel lift (~2 cm thick total, 3 layers). Each lift layer is removed as pain allows, every 2 to 3 days. The goal is full weight-bearing with the foot flat 5 to 6 weeks after surgery. Physical therapy focusing on ankle motion and gentle Achilles stretching and strengthening is started 5 to 6 weeks after surgery, depending on progression and functional needs. Between 8 and 12 weeks after surgery, the patient is transitioned to normal shoe wear with increased activities. Running and jumping are allowed, as pain and swelling allow, starting at 12 weeks.
Although preliminary outcomes and experience with the Achilles Midsubstance SpeedBridge have been favorable, long-term clinical and functional studies are needed to determine the specific advantages and disadvantages of this new technique relative to other repairs. The main benefits observed thus far are reduced subjective knot tying and tensioning, decreased reliance on suture fixation in compromised tissue at the rupture site, reduced risk of FiberWire knot irritation of superficial soft tissues, lower risk of distal suture pullout, and earlier mobilization owing to bony fixation of the tendon. Potential complications include anchor-site heel pain caused by prominent anchors or by the bone edema that occurs when a patient increases physical activity by a significant amount at 12 weeks.9 Heel pain caused by bone edema resolves by 20 weeks without intervention.
Stress shielding of the distal Achilles tendon is a theoretical concern given the tendon–bone construct, but there have been no reports of tendon atrophy or repair failure caused by stress shielding. The original PARS technique was often used to create Achilles tension with the ankle maximally plantar flexed—the idea being that the tendon would gradually stretch over time.1 Overtensioning the Achilles repair is a potential complication with the SpeedBridge, as the distal anchors provide a more rigid point of distal fixation. Surgeons can avoid this complication by cycling the sutures to remove any residual creep and then tensioning the Achilles according to the contralateral limb and/or palpating tendon opposition at the rupture site.
Overall, this new limited-incision knotless Achilles tendon repair technique allows for minimal soft-tissue dissection, restoration of Achilles musculotendinous length, and direct tendon-to-bone fixation. Early results are promising, but long-term clinical outcomes and comparative analysis are needed. In addition, many details of this technique must be clarified—including incidence of short- and long-term complications in larger cohorts, optimal suture material and configuration, and risks and benefits of immediate (<2 weeks) and delayed (2-4 weeks) weight-bearing.
Am J Orthop. 2016;45(7):E487-E492. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Hsu AR, Jones CP, Cohen BE, Davis WH, Ellington JK, Anderson RB. Clinical outcomes and complications of Percutaneous Achilles Repair System versus open technique for acute Achilles tendon ruptures. Foot Ankle Int. 2015;36(11):1279-1286.
2. Raikin SM, Garras DN, Krapchev PV. Achilles tendon injuries in a United States population. Foot Ankle Int. 2013;34(4):475-480.
3. Chiodo CP, Glazebrook M, Bluman EM, et al; American Academy of Orthopaedic Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on treatment of Achilles tendon rupture. J Bone Joint Surg Am. 2010;92(14):2466-2468.
4. Chiodo CP, Glazebrook M, Bluman EM, et al; American Academy of Orthopaedic Surgeons. Diagnosis and treatment of acute Achilles tendon rupture. J Am Acad Orthop Surg. 2010;18(8):503-510.
5. Khan RJ, Fick D, Keogh A, Crawford J, Brammar T, Parker M. Treatment of acute Achilles tendon ruptures. A meta-analysis of randomized, controlled trials. J Bone Joint Surg Am. 2005;87(10):2202-2210.
6. Renninger CH, Kuhn K, Fellars T, Youngblood S, Bellamy J. Operative and nonoperative management of Achilles tendon ruptures in active duty military population. Foot Ankle Int. 2016;37(3):269-273.
7. Khan RJ, Carey Smith RL. Surgical interventions for treating acute Achilles tendon ruptures. Cochrane Database Syst Rev. 2010;(9):CD003674.
8. McCullough KA, Shaw CM, Anderson RB. Mini-open repair of Achilles rupture in the National Football League. J Surg Orthop Adv. 2014;23(4):179-183.
9. McWilliam JR, Mackay G. The internal brace for midsubstance Achilles ruptures. Foot Ankle Int. 2016;37(7):794-800.
10. Clanton TO, Haytmanek CT, Williams BT, et al. A biomechanical comparison of an open repair and 3 minimally invasive percutaneous Achilles tendon repair techniques during a simulated, progressive rehabilitation protocol. Am J Sports Med. 2015;43(8):1957-1964.
11. Aoki M, Ogiwara N, Ohta T, Nabeta Y. Early active motion and weightbearing after cross-stitch Achilles tendon repair. Am J Sports Med. 1998;26(6):794-800.
12. Kangas J, Pajala A, Ohtonen P, Leppilahti J. Achilles tendon elongation after rupture repair: a randomized comparison of 2 postoperative regimens. Am J Sports Med. 2007;35(1):59-64.
13. Kangas J, Pajala A, Siira P, Hämäläinen M, Leppilahti J. Early functional treatment versus early immobilization in tension of the musculotendinous unit after Achilles rupture repair: a prospective, randomized, clinical study. J Trauma. 2003;54(6):1171-1180.
1. Hsu AR, Jones CP, Cohen BE, Davis WH, Ellington JK, Anderson RB. Clinical outcomes and complications of Percutaneous Achilles Repair System versus open technique for acute Achilles tendon ruptures. Foot Ankle Int. 2015;36(11):1279-1286.
2. Raikin SM, Garras DN, Krapchev PV. Achilles tendon injuries in a United States population. Foot Ankle Int. 2013;34(4):475-480.
3. Chiodo CP, Glazebrook M, Bluman EM, et al; American Academy of Orthopaedic Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on treatment of Achilles tendon rupture. J Bone Joint Surg Am. 2010;92(14):2466-2468.
4. Chiodo CP, Glazebrook M, Bluman EM, et al; American Academy of Orthopaedic Surgeons. Diagnosis and treatment of acute Achilles tendon rupture. J Am Acad Orthop Surg. 2010;18(8):503-510.
5. Khan RJ, Fick D, Keogh A, Crawford J, Brammar T, Parker M. Treatment of acute Achilles tendon ruptures. A meta-analysis of randomized, controlled trials. J Bone Joint Surg Am. 2005;87(10):2202-2210.
6. Renninger CH, Kuhn K, Fellars T, Youngblood S, Bellamy J. Operative and nonoperative management of Achilles tendon ruptures in active duty military population. Foot Ankle Int. 2016;37(3):269-273.
7. Khan RJ, Carey Smith RL. Surgical interventions for treating acute Achilles tendon ruptures. Cochrane Database Syst Rev. 2010;(9):CD003674.
8. McCullough KA, Shaw CM, Anderson RB. Mini-open repair of Achilles rupture in the National Football League. J Surg Orthop Adv. 2014;23(4):179-183.
9. McWilliam JR, Mackay G. The internal brace for midsubstance Achilles ruptures. Foot Ankle Int. 2016;37(7):794-800.
10. Clanton TO, Haytmanek CT, Williams BT, et al. A biomechanical comparison of an open repair and 3 minimally invasive percutaneous Achilles tendon repair techniques during a simulated, progressive rehabilitation protocol. Am J Sports Med. 2015;43(8):1957-1964.
11. Aoki M, Ogiwara N, Ohta T, Nabeta Y. Early active motion and weightbearing after cross-stitch Achilles tendon repair. Am J Sports Med. 1998;26(6):794-800.
12. Kangas J, Pajala A, Ohtonen P, Leppilahti J. Achilles tendon elongation after rupture repair: a randomized comparison of 2 postoperative regimens. Am J Sports Med. 2007;35(1):59-64.
13. Kangas J, Pajala A, Siira P, Hämäläinen M, Leppilahti J. Early functional treatment versus early immobilization in tension of the musculotendinous unit after Achilles rupture repair: a prospective, randomized, clinical study. J Trauma. 2003;54(6):1171-1180.
Pediatric OSA improved with oral montelukast
The majority of children with obstructive sleep apnea (OSA) who took oral montelukast showed reductions in their apnea-hypopnea index (AHI) scores, according to the results of a randomized, double-blind placebo-controlled study. Typically, OSA in children is treated with adenotonsillectomy, explained Leila Kheirandish-Gozal, MD, director of clinical sleep research at the University of Chicago, and her colleagues. However, in this study, children were given either montelukast or placebo for 16 weeks and then participated in an overnight polysomnographic study. Seventy-one percent of the patients who took montelukast had fewer AHI events per hour of total sleep time at the end of the study. To learn more, see Family Practice News: http://www.mdedge.com/familypracticenews/article/116479/pulmonology/pediatric-osa-improved-oral-montelukast.
The majority of children with obstructive sleep apnea (OSA) who took oral montelukast showed reductions in their apnea-hypopnea index (AHI) scores, according to the results of a randomized, double-blind placebo-controlled study. Typically, OSA in children is treated with adenotonsillectomy, explained Leila Kheirandish-Gozal, MD, director of clinical sleep research at the University of Chicago, and her colleagues. However, in this study, children were given either montelukast or placebo for 16 weeks and then participated in an overnight polysomnographic study. Seventy-one percent of the patients who took montelukast had fewer AHI events per hour of total sleep time at the end of the study. To learn more, see Family Practice News: http://www.mdedge.com/familypracticenews/article/116479/pulmonology/pediatric-osa-improved-oral-montelukast.
The majority of children with obstructive sleep apnea (OSA) who took oral montelukast showed reductions in their apnea-hypopnea index (AHI) scores, according to the results of a randomized, double-blind placebo-controlled study. Typically, OSA in children is treated with adenotonsillectomy, explained Leila Kheirandish-Gozal, MD, director of clinical sleep research at the University of Chicago, and her colleagues. However, in this study, children were given either montelukast or placebo for 16 weeks and then participated in an overnight polysomnographic study. Seventy-one percent of the patients who took montelukast had fewer AHI events per hour of total sleep time at the end of the study. To learn more, see Family Practice News: http://www.mdedge.com/familypracticenews/article/116479/pulmonology/pediatric-osa-improved-oral-montelukast.
VIDEO: Don’t be surprised by weight gain in men after HCV cure
Researchers found that men, but not women, who had achieved sustained virologic response (SVR) after treatment for hepatitis C virus (HCV) had a small but significant weight gain, according to a single-center retrospective study. Liver fat also increased significantly in men after SVR was achieved, according to noninvasive assessments. The researchers believe that social, and not biochemical or mechanistic, reasons may be behind the weight gain and increased hepatic steatosis. A video interview with one of the researchers can be seen at Family Practice News: http://www.mdedge.com/familypracticenews/article/118172/obesity/video-dont-be-surprised-weight-gain-men-after-hcv-cure.
Researchers found that men, but not women, who had achieved sustained virologic response (SVR) after treatment for hepatitis C virus (HCV) had a small but significant weight gain, according to a single-center retrospective study. Liver fat also increased significantly in men after SVR was achieved, according to noninvasive assessments. The researchers believe that social, and not biochemical or mechanistic, reasons may be behind the weight gain and increased hepatic steatosis. A video interview with one of the researchers can be seen at Family Practice News: http://www.mdedge.com/familypracticenews/article/118172/obesity/video-dont-be-surprised-weight-gain-men-after-hcv-cure.
Researchers found that men, but not women, who had achieved sustained virologic response (SVR) after treatment for hepatitis C virus (HCV) had a small but significant weight gain, according to a single-center retrospective study. Liver fat also increased significantly in men after SVR was achieved, according to noninvasive assessments. The researchers believe that social, and not biochemical or mechanistic, reasons may be behind the weight gain and increased hepatic steatosis. A video interview with one of the researchers can be seen at Family Practice News: http://www.mdedge.com/familypracticenews/article/118172/obesity/video-dont-be-surprised-weight-gain-men-after-hcv-cure.
VIDEO: Bariatric surgery may protect against heart failure
Results of a new 40,000-patient Swedish observational study provide the strongest evidence to date suggesting a causal relationship between bariatric surgery and reduced risk of heart failure, according to Johan Sundström, MD. The study, which included patients drawn from 2 large Swedish national registries, demonstrated that bariatric surgery was associated with a 46% reduction in the incidence of heart failure during a median 4.1 years of follow-up, compared with an intensive lifestyle modification program for weight loss.
“A great way of studying causality is to take away the exposure and note what happens to the outcome. If there’s a causal link, then if you take away the risk factor—in this case, obesity—the disease should go away,” Dr. Sundström explained. Further details and a video interview are available at Cardiology News: http://www.mdedge.com/ecardiologynews/article/118204/heart-failure/video-bariatric-surgery-may-protect-against-heart?channel=224.
Results of a new 40,000-patient Swedish observational study provide the strongest evidence to date suggesting a causal relationship between bariatric surgery and reduced risk of heart failure, according to Johan Sundström, MD. The study, which included patients drawn from 2 large Swedish national registries, demonstrated that bariatric surgery was associated with a 46% reduction in the incidence of heart failure during a median 4.1 years of follow-up, compared with an intensive lifestyle modification program for weight loss.
“A great way of studying causality is to take away the exposure and note what happens to the outcome. If there’s a causal link, then if you take away the risk factor—in this case, obesity—the disease should go away,” Dr. Sundström explained. Further details and a video interview are available at Cardiology News: http://www.mdedge.com/ecardiologynews/article/118204/heart-failure/video-bariatric-surgery-may-protect-against-heart?channel=224.
Results of a new 40,000-patient Swedish observational study provide the strongest evidence to date suggesting a causal relationship between bariatric surgery and reduced risk of heart failure, according to Johan Sundström, MD. The study, which included patients drawn from 2 large Swedish national registries, demonstrated that bariatric surgery was associated with a 46% reduction in the incidence of heart failure during a median 4.1 years of follow-up, compared with an intensive lifestyle modification program for weight loss.
“A great way of studying causality is to take away the exposure and note what happens to the outcome. If there’s a causal link, then if you take away the risk factor—in this case, obesity—the disease should go away,” Dr. Sundström explained. Further details and a video interview are available at Cardiology News: http://www.mdedge.com/ecardiologynews/article/118204/heart-failure/video-bariatric-surgery-may-protect-against-heart?channel=224.
Interrupting oral anticoagulation in AF carries high thromboembolic cost
Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.
The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings may encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons. More on the findings of this analysis can be found at Cardiology News: http://www.mdedge.com/ecardiologynews/article/116905/arrhythmias-ep/interrupting-oral-anticoagulation-af-carries-high.
Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.
The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings may encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons. More on the findings of this analysis can be found at Cardiology News: http://www.mdedge.com/ecardiologynews/article/116905/arrhythmias-ep/interrupting-oral-anticoagulation-af-carries-high.
Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.
The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings may encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons. More on the findings of this analysis can be found at Cardiology News: http://www.mdedge.com/ecardiologynews/article/116905/arrhythmias-ep/interrupting-oral-anticoagulation-af-carries-high.
Preventing infection after cesarean delivery: 5 more evidence-based measures to consider
In part 1 of our review on preventing postcesarean infection, we critically evaluated methods of skin preparation and administration of prophylactic antibiotics. In part 2, we address preoperative cleansing of the vagina with an antiseptic solution, preoperative bathing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.
Related article:
Preventing infection after cesarean delivery: Evidence-based guidance
CASE: Should vaginal cleansing be performed prior to cesarean delivery?
An 18-year-old primigravid woman at 41 weeks’ gestation has been in labor for 16 hours, and now has an arrest of descent at 0 station. An intrauterine pressure catheter and scalp electrode have been in place for the same length of time. The patient has had 9 internal examinations during the period of membrane rupture. As you are preparing to scrub the patient’s abdomen, the third-year medical student asks, “When I was on the Gynecology Service, I saw the doctors wash the vagina with an antiseptic solution before they performed a vaginal hysterectomy. Should we also do that before we operate on this patient?”
Preoperative vaginal cleansing
A preoperative antiseptic vaginal scrub is often used as an additional step to help reduce postcesarean infection.
Does cleansing the vagina with povidone-iodine before surgery further reduce the risk of endometritis and wound infection?
Multiple studies have sought to determine if cleansing the vagina with an antiseptic solution further reduces the incidence of postcesarean infection beyond what can be achieved with systemic antibiotic prophylaxis. These studies typically have focused on 3 specific outcomes: endometritis, wound (surgical site) infection, and febrile morbidity. The term febrile morbidity is defined as a temperature ≥100.4°F (38°C) on any 2 postoperative days excluding the first 24 hours. However, many patients who meet the standard definition of febrile morbidity may not have a proven infection and will not require treatment with antibiotics. The more precise measures of outcome are distinctly symptomatic infections, such as endometritis and wound infection, although, as noted in the review of published studies below, some authors continue to use the term febrile morbidity as one measure of postoperative complications.
In a randomized, placebo-controlled trial (RCT) of 308 women having a nonemergent cesarean delivery, Starr and colleagues reported a decreased incidence of postoperative endometritis in women who received a 30-second vaginal scrub with povidone-iodine compared with women who received only an abdominal scrub (7.0% vs 14.5%, P<.05).1 The groups did not differ in the frequency of wound infection (0.7% vs 1.2%, P = .4) or febrile morbidity (23.9% vs 28.3%, P = .4).1
In another RCT, Haas and colleagues found that preoperative vaginal cleansing with povidone-iodine compared with an abdominal scrub alone was associated with a decreased incidence of a composite measure of postoperative morbidity (6.5% vs 11.7%; relative risk [RR], 0.55; 95% confidence interval [CI], 0.26–1.11; P = .11).2 The postoperative composite included fever, endometritis, sepsis, readmission, and wound infection.
Subsequently, Asghania and associates conducted a double-blind, nonrandomized study of 568 women having cesarean delivery who received an abdominal scrub plus a 30-second vaginal scrub with povidone-iodine or received an abdominal scrub alone.3 They documented a decreased incidence of postoperative endometritis in the women who received the combined scrub (1.4% vs 2.5%; P = .03, adjusted odds ratio [AOR], 0.03; 95% CI, 0.008–0.7). The authors observed no significant difference in febrile morbidity (4.9% vs 6.0%; P = .73) or wound infection (3.5% vs 3.2%; P = .5).3
Yildirim and colleagues conducted an RCT comparing rates of infection in 334 women who received an abdominal scrub plus vaginal cleansing with povidone-iodine and 336 patients who had only a standard abdominal scrub.4 They documented a decreased incidence of endometritis in women who received the vaginal scrub (6.9% vs 11.6%; P = .04; RR for infection in the control group, 1.69; 95% CI, 1.03–2.76.) The authors found no difference in febrile morbidity (16.5% vs 18.2%; P = .61) or wound infection (1.8% vs 2.7%; P = .60). Of note, in excluding from the analysis women who had ruptured membranes or who were in labor, the investigators found no differences in outcome, indicating that the greatest impact of vaginal cleansing was in the highest risk patients.
In 2014, Haas and associates published a Cochrane review evaluating the effectiveness of preoperative vaginal cleansing with povidone-iodine.5 The authors reviewed 7 studies that analyzed outcomes in 2,635 women. They concluded that vaginal preparation with povidone-iodine at the time of cesarean delivery significantly decreased postoperative endometritis when compared with the control group (4.3% vs 8.3%; RR, 0.45; 95% CI, 0.25–0.81). They also noted that the most profound impact of vaginal cleansing was in women who were in labor before delivery (7.4% vs 13.0%; RR, 0.56; 95% CI, 0.34–0.95) and in women with ruptured membranes at the time of delivery (4.3% vs 17.9%; RR, 0.24; 95% CI, 0.10–0.55). The authors did not find a significant difference in postoperative wound infection or frequency of fever in women who received the vaginal scrub.
Related article:
STOP using instruments to assist with delivery of the head at cesarean
A notable exception to the beneficial outcomes reported above was the study by Reid et al.6 These authors randomly assigned 247 women having cesarean delivery to an abdominal scrub plus vaginal scrub with povidone-iodine and assigned 251 women to only an abdominal scrub. The authors were unable to document any significant difference between the groups with respect to frequency of fever, endometritis, and wound infection.
Other methods of vaginal preparation also have been studied. For example, Pitt and colleagues conducted a double-blind RCT of 224 women having cesarean delivery and compared preoperative metronidazole vaginal gel with placebo.7 Most of the patients in this trial also received systemic antibiotic prophylaxis after the umbilical cord was clamped. The authors demonstrated a decreased incidence of postcesarean endometritis in women who received the intravaginal antibiotic gel (7% vs 17%; RR, 0.42; 95% CI, 0.19–0.92). There was no difference in febrile morbidity (13% vs 19%; P = .28) or wound infection (4% vs 3%, P = .50).
What the evidence says
Consider vaginal preparation with povidone-iodine at the time of cesarean delivery to reduce the risk of postpartum endometritis. Do not expect this intervention to significantly reduce the frequency of wound infection. Vaginal cleansing is of most benefit to women who have ruptured membranes or are in labor at the time of delivery (Level I Evidence, Level A Recommendation; TABLE). Whether vaginal preparation with chlorhexidine with 4% alcohol would have the same beneficial effect has not been studied in a systematic manner.
Placenta extraction, closure techniques
Evidence suggests that employing certain intraoperative approaches helps reduce the incidence of postcesarean infection.
What other measures help prevent infection following cesarean surgery?
One other measure known to decrease the risk of postcesarean endometritis is removing the placenta by exerting traction on the umbilical cord rather than extracting it manually. In one of the first descriptions of this intervention, Lasley and associates showed that, in high-risk patients who also received intravenous antibiotic prophylaxis after cord clamping, the rate of postoperative endometritis was 15% in the group that had spontaneous delivery of the placenta compared with 27% in women who had manual extraction (RR, 0.6; 95% CI, 0.3–0.9; P = .02).8 A recent Cochrane review that included multiple subsequent reports confirmed this observation (Level I Evidence, Level A Recommendation; TABLE, page 2).9
Abdominal wall closure. Two other interventions are valuable in decreasing the frequency of deep and superficial wound infection. In patients whose subcutaneous layer is >2 cm thick, closure of the deep subcutaneous tissue significantly reduces the risk of wound seroma, hematoma, and infection.10 In addition, closure of the skin edges with a subcuticular suture, as opposed to surgical staples, significantly reduces the frequency of superficial wound complications (Level I Evidence, Level A Recommendation; TABLE, page 2).11 Poliglecaprone 25, polyglactin 910, and polyglycolic acid suture, 3-0 or 4-0 gauge, are excellent suture choices for this closure.
Related article:
Does one particular cesarean technique confer better maternal and neonatal outcomes?
CASE
Planned cesarean delivery: Is preoperative antiseptic bathing warranted?
A 33-year-old woman (G2P1001) at 39 weeks’ gestation is scheduled for a repeat low transverse cesarean delivery. In addition to planning to implement the measures discussed above, her clinician is considering whether to recommend that the patient bathe with an antiseptic solution, such as chlorhexidine, the day before the procedure.
Preoperative antiseptic bathing
The concept of bathing with an antiseptic solution before surgery to prevent surgical site infections (SSIs) has been considered for many years. Intuitively, if the body’s resident and transient skin flora are decreased preoperatively with whole-body antiseptic washing, then the overall pathogen burden should be decreased and the risk of SSI also should be reduced. Historically, chlorhexidine preparations have been used as preoperative antiseptic solutions because they are so effective in reducing colony counts of skin flora, especially staphylococci.12 Although preoperative antiseptic washing definitely reduces the concentration of skin bacteria, the data regarding reduction in SSI are inconsistent. Of particular note, there are no studies investigating the impact of preoperative antiseptic bathing in women having cesarean delivery.
Does preop bathing with an antiseptic reduce infection risk?
One of the first studies evaluating preoperative antiseptic washing was published by Cruse and Foord in 1980.13 In this 10-year prospective investigation, the authors demonstrated that patients who underwent preoperative washing with a hexachlorophene solution had fewer SSIs compared with those who washed with a nonmedicated soap and those who did not wash at all. Subsequent studies by Brady et al in 1990,14 Wilcox et al in 2003,15 and Colling et al in 201516 all showed a decrease in the rate of SSIs with preoperative antiseptic washing, and the authors strongly supported this intervention. However, care must be taken when interpreting the results of these cohort investigations because in some cases antiseptic washing was not the only preoperative intervention. Thus, it is difficult to ascertain the true benefit of antiseptic washing alone.14,15 Moreover, in one study, preoperative antiseptic washing did not decrease the overall incidence of SSIs, just those caused by Staphylococcus aureus and methicillin-resistant S aureus (MRSA).16
Authors of 3 recent reviews have assessed the relationship between preoperative antiseptic washing and SSIs. Webster and Osborne analyzed 7 RCTs in a Cochrane review.17 All trials used 4% chlorhexidine gluconate as the antiseptic, and they included a total of 10,157 patients. The authors concluded that bathing with chlorhexidine did not significantly reduce SSIs compared with either placebo (RR, 0.91; 95% CI, 0.8–1.04) or bar soap (RR, 1.02; 95% CI, 0.57–1.84). Three additional studies in this review compared chlorhexidine bathing with no washing. One study showed a significant reduction of SSIs after the patients bathed with chlorhexidine (RR, 0.36; 95% CI, 0.17–0.79); the other 2 studies demonstrated no significant difference in outcome.
Kamel and colleagues conducted a recent systematic review that included 20 randomized and nonrandomized studies (n = 9,520); while the authors concluded that showering with an antiseptic solution reduced skin flora, they could not confirm that it produced a significant reduction in infection.18 Finally, in a meta-analysis that included 16 randomized and nonrandomized studies with 17,932 patients, Chlebicki and associates concluded that there was no significant reduction in SSIs with whole-body bathing with chlorhexidine compared with bathing with soap or placebo or with no bathing (RR, 0.90; 95% CI, 0.77–1.05; P = .19).19 A recent report from the World Health Organization confirmed these observations, although the report did not specifically focus on patients who had had a cesarean delivery.20
What the evidence says
Although chlorhexidine bathing reduces skin flora, especially in the number of staphylococcal species, this effect does not necessarily translate into a reduction of SSIs. Therefore, we recommend against routine chlorhexidine bathing before cesarean delivery, although we acknowledge that there is no apparent harm associated with this practice, assuming that the patient is not allergic to the medicated soap (Level II Evidence, Level C Recommendation; TABLE, page 2).
Did you read Part 1 of this series?
Preventing infection after cesarean delivery: Evidence-based guidance, Part 1
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Starr RV, Zurawski J, Ismail M. Preoperative vaginal preparation with povidone-iodine and the risk of postcesarean endometritis. Obstet Gynecol. 2005;105(5 pt 1):1024–1029.
- Haas DM, Pazouki F, Smith RR, et al. Vaginal cleansing before cesarean delivery to reduce postoperative infectious morbidity: a randomized controlled trial. Am J Obstet Gynecol. 2010;202(3):310.e1–e6.
- Asghania M, Mirblouk F, Shakiba M, Faraji R. Preoperative vaginal preparation with povidone-iodine on post-caesarean infectious morbidity. J Obstet Gynaecol. 2011;31(5):400–403.
- Yildirim G, Güngördük K, Asicioglu O, et al. Does vaginal preparation with povidone-iodine prior to caesarean delivery reduce the risk of endometritis? A randomized controlled trial. J Matern Fetal Neonatal Med. 2012;25(11):2316–2321.
- Haas DM, Morgan S, Contreras K. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Sys Rev. 2014;(12):CD007892.
- Reid VC, Hartmann KE, McMahon M, Fry EP. Vaginal preparation with povidone iodine and postcesarean infectious morbidity: a randomized controlled trial. Obstet Gynecol. 2001;97(1):147–152.
- Pitt C, Sanchez-Ramos L, Kaunitz AM. Adjunctive intravaginal metronidazole for the prevention of postcesarean endometritis: a randomized controlled trial. Obstet Gynecol. 2001;98(5 pt 1):745–750.
- Lasley DS, Eblen A, Yancey MK, Duff P. The effect of placental removal method on the incidence of postcesarean infections. Am J Obstet Gynecol. 1997;176(6):1250–1254.
- Methods of delivering the placenta at caesarean section [comment]. Obstet Gynecol. 2008;112(5):1173–1174.
- Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 pt 1):974–980.
- Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a metaanalysis. Am J Obstet Gynecol. 2015;212(5):621.e1–e10.
- , , , . Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers . Ann Thorac Surg. 1988 ; 45(1) : 35 –3 8 .
- , . The epidemiology of wound infection. A 10-year prospective study of 62,939 wounds . Surg Clin North Am. 1980 ; 60 ( 1 ): 27 – 40 .
- , , , Harkness JL. Successful control of endemic MRSA in a cardiothoracic surgical unit . Med J Aust. 1990 ; 152(5) : 240 –24 5 .
- , , , et al. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J Hosp Infect. 2003 ; 54(3) : 196 – 201 .
- , , , Banton K, Bellman G. Pre-operative antiseptic shower and bath policy decreases the rate of S aureus and methicillin-resistant S aureus surgical site infections in patients undergoing joint arthroplasty . Surg Infect. 2015 ; 16(2):124–132.
- Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. 2012;(9):CD004985.
- , , , Mierzwinski-Urban M, Embil JM. Preoperative skin antiseptic preparations for preventing surgical site infections: a systematic review . Infect Control Hosp Epidemiol. 2012 ; 33(6) : 608 – 617 .
- , , , Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis . Am J Infect Control. 2013 ; 41(2) : 167 –1 73 .
- Global guidelines for the prevention of surgical site infection. Geneva, Switzerland: World Health Organization; November 2016. http://www.who.int/gpsc/global-guidelines-web.pdf?ua=1. Accessed November 9, 2016.
Dr. Patrick is a Maternal-Fetal Medicine Fellow in the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
Dr. Deatsman is an Obstetrician-Gynecologist, Bronson Methodist Hospital, Kalamazoo, Michigan.
Dr. Duff is Associate Dean for Student Affairs and Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Patrick is a Maternal-Fetal Medicine Fellow in the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
Dr. Deatsman is an Obstetrician-Gynecologist, Bronson Methodist Hospital, Kalamazoo, Michigan.
Dr. Duff is Associate Dean for Student Affairs and Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
Dr. Patrick is a Maternal-Fetal Medicine Fellow in the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
Dr. Deatsman is an Obstetrician-Gynecologist, Bronson Methodist Hospital, Kalamazoo, Michigan.
Dr. Duff is Associate Dean for Student Affairs and Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.
The authors report no financial relationships relevant to this article.
In part 1 of our review on preventing postcesarean infection, we critically evaluated methods of skin preparation and administration of prophylactic antibiotics. In part 2, we address preoperative cleansing of the vagina with an antiseptic solution, preoperative bathing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.
Related article:
Preventing infection after cesarean delivery: Evidence-based guidance
CASE: Should vaginal cleansing be performed prior to cesarean delivery?
An 18-year-old primigravid woman at 41 weeks’ gestation has been in labor for 16 hours, and now has an arrest of descent at 0 station. An intrauterine pressure catheter and scalp electrode have been in place for the same length of time. The patient has had 9 internal examinations during the period of membrane rupture. As you are preparing to scrub the patient’s abdomen, the third-year medical student asks, “When I was on the Gynecology Service, I saw the doctors wash the vagina with an antiseptic solution before they performed a vaginal hysterectomy. Should we also do that before we operate on this patient?”
Preoperative vaginal cleansing
A preoperative antiseptic vaginal scrub is often used as an additional step to help reduce postcesarean infection.
Does cleansing the vagina with povidone-iodine before surgery further reduce the risk of endometritis and wound infection?
Multiple studies have sought to determine if cleansing the vagina with an antiseptic solution further reduces the incidence of postcesarean infection beyond what can be achieved with systemic antibiotic prophylaxis. These studies typically have focused on 3 specific outcomes: endometritis, wound (surgical site) infection, and febrile morbidity. The term febrile morbidity is defined as a temperature ≥100.4°F (38°C) on any 2 postoperative days excluding the first 24 hours. However, many patients who meet the standard definition of febrile morbidity may not have a proven infection and will not require treatment with antibiotics. The more precise measures of outcome are distinctly symptomatic infections, such as endometritis and wound infection, although, as noted in the review of published studies below, some authors continue to use the term febrile morbidity as one measure of postoperative complications.
In a randomized, placebo-controlled trial (RCT) of 308 women having a nonemergent cesarean delivery, Starr and colleagues reported a decreased incidence of postoperative endometritis in women who received a 30-second vaginal scrub with povidone-iodine compared with women who received only an abdominal scrub (7.0% vs 14.5%, P<.05).1 The groups did not differ in the frequency of wound infection (0.7% vs 1.2%, P = .4) or febrile morbidity (23.9% vs 28.3%, P = .4).1
In another RCT, Haas and colleagues found that preoperative vaginal cleansing with povidone-iodine compared with an abdominal scrub alone was associated with a decreased incidence of a composite measure of postoperative morbidity (6.5% vs 11.7%; relative risk [RR], 0.55; 95% confidence interval [CI], 0.26–1.11; P = .11).2 The postoperative composite included fever, endometritis, sepsis, readmission, and wound infection.
Subsequently, Asghania and associates conducted a double-blind, nonrandomized study of 568 women having cesarean delivery who received an abdominal scrub plus a 30-second vaginal scrub with povidone-iodine or received an abdominal scrub alone.3 They documented a decreased incidence of postoperative endometritis in the women who received the combined scrub (1.4% vs 2.5%; P = .03, adjusted odds ratio [AOR], 0.03; 95% CI, 0.008–0.7). The authors observed no significant difference in febrile morbidity (4.9% vs 6.0%; P = .73) or wound infection (3.5% vs 3.2%; P = .5).3
Yildirim and colleagues conducted an RCT comparing rates of infection in 334 women who received an abdominal scrub plus vaginal cleansing with povidone-iodine and 336 patients who had only a standard abdominal scrub.4 They documented a decreased incidence of endometritis in women who received the vaginal scrub (6.9% vs 11.6%; P = .04; RR for infection in the control group, 1.69; 95% CI, 1.03–2.76.) The authors found no difference in febrile morbidity (16.5% vs 18.2%; P = .61) or wound infection (1.8% vs 2.7%; P = .60). Of note, in excluding from the analysis women who had ruptured membranes or who were in labor, the investigators found no differences in outcome, indicating that the greatest impact of vaginal cleansing was in the highest risk patients.
In 2014, Haas and associates published a Cochrane review evaluating the effectiveness of preoperative vaginal cleansing with povidone-iodine.5 The authors reviewed 7 studies that analyzed outcomes in 2,635 women. They concluded that vaginal preparation with povidone-iodine at the time of cesarean delivery significantly decreased postoperative endometritis when compared with the control group (4.3% vs 8.3%; RR, 0.45; 95% CI, 0.25–0.81). They also noted that the most profound impact of vaginal cleansing was in women who were in labor before delivery (7.4% vs 13.0%; RR, 0.56; 95% CI, 0.34–0.95) and in women with ruptured membranes at the time of delivery (4.3% vs 17.9%; RR, 0.24; 95% CI, 0.10–0.55). The authors did not find a significant difference in postoperative wound infection or frequency of fever in women who received the vaginal scrub.
Related article:
STOP using instruments to assist with delivery of the head at cesarean
A notable exception to the beneficial outcomes reported above was the study by Reid et al.6 These authors randomly assigned 247 women having cesarean delivery to an abdominal scrub plus vaginal scrub with povidone-iodine and assigned 251 women to only an abdominal scrub. The authors were unable to document any significant difference between the groups with respect to frequency of fever, endometritis, and wound infection.
Other methods of vaginal preparation also have been studied. For example, Pitt and colleagues conducted a double-blind RCT of 224 women having cesarean delivery and compared preoperative metronidazole vaginal gel with placebo.7 Most of the patients in this trial also received systemic antibiotic prophylaxis after the umbilical cord was clamped. The authors demonstrated a decreased incidence of postcesarean endometritis in women who received the intravaginal antibiotic gel (7% vs 17%; RR, 0.42; 95% CI, 0.19–0.92). There was no difference in febrile morbidity (13% vs 19%; P = .28) or wound infection (4% vs 3%, P = .50).
What the evidence says
Consider vaginal preparation with povidone-iodine at the time of cesarean delivery to reduce the risk of postpartum endometritis. Do not expect this intervention to significantly reduce the frequency of wound infection. Vaginal cleansing is of most benefit to women who have ruptured membranes or are in labor at the time of delivery (Level I Evidence, Level A Recommendation; TABLE). Whether vaginal preparation with chlorhexidine with 4% alcohol would have the same beneficial effect has not been studied in a systematic manner.
Placenta extraction, closure techniques
Evidence suggests that employing certain intraoperative approaches helps reduce the incidence of postcesarean infection.
What other measures help prevent infection following cesarean surgery?
One other measure known to decrease the risk of postcesarean endometritis is removing the placenta by exerting traction on the umbilical cord rather than extracting it manually. In one of the first descriptions of this intervention, Lasley and associates showed that, in high-risk patients who also received intravenous antibiotic prophylaxis after cord clamping, the rate of postoperative endometritis was 15% in the group that had spontaneous delivery of the placenta compared with 27% in women who had manual extraction (RR, 0.6; 95% CI, 0.3–0.9; P = .02).8 A recent Cochrane review that included multiple subsequent reports confirmed this observation (Level I Evidence, Level A Recommendation; TABLE, page 2).9
Abdominal wall closure. Two other interventions are valuable in decreasing the frequency of deep and superficial wound infection. In patients whose subcutaneous layer is >2 cm thick, closure of the deep subcutaneous tissue significantly reduces the risk of wound seroma, hematoma, and infection.10 In addition, closure of the skin edges with a subcuticular suture, as opposed to surgical staples, significantly reduces the frequency of superficial wound complications (Level I Evidence, Level A Recommendation; TABLE, page 2).11 Poliglecaprone 25, polyglactin 910, and polyglycolic acid suture, 3-0 or 4-0 gauge, are excellent suture choices for this closure.
Related article:
Does one particular cesarean technique confer better maternal and neonatal outcomes?
CASE
Planned cesarean delivery: Is preoperative antiseptic bathing warranted?
A 33-year-old woman (G2P1001) at 39 weeks’ gestation is scheduled for a repeat low transverse cesarean delivery. In addition to planning to implement the measures discussed above, her clinician is considering whether to recommend that the patient bathe with an antiseptic solution, such as chlorhexidine, the day before the procedure.
Preoperative antiseptic bathing
The concept of bathing with an antiseptic solution before surgery to prevent surgical site infections (SSIs) has been considered for many years. Intuitively, if the body’s resident and transient skin flora are decreased preoperatively with whole-body antiseptic washing, then the overall pathogen burden should be decreased and the risk of SSI also should be reduced. Historically, chlorhexidine preparations have been used as preoperative antiseptic solutions because they are so effective in reducing colony counts of skin flora, especially staphylococci.12 Although preoperative antiseptic washing definitely reduces the concentration of skin bacteria, the data regarding reduction in SSI are inconsistent. Of particular note, there are no studies investigating the impact of preoperative antiseptic bathing in women having cesarean delivery.
Does preop bathing with an antiseptic reduce infection risk?
One of the first studies evaluating preoperative antiseptic washing was published by Cruse and Foord in 1980.13 In this 10-year prospective investigation, the authors demonstrated that patients who underwent preoperative washing with a hexachlorophene solution had fewer SSIs compared with those who washed with a nonmedicated soap and those who did not wash at all. Subsequent studies by Brady et al in 1990,14 Wilcox et al in 2003,15 and Colling et al in 201516 all showed a decrease in the rate of SSIs with preoperative antiseptic washing, and the authors strongly supported this intervention. However, care must be taken when interpreting the results of these cohort investigations because in some cases antiseptic washing was not the only preoperative intervention. Thus, it is difficult to ascertain the true benefit of antiseptic washing alone.14,15 Moreover, in one study, preoperative antiseptic washing did not decrease the overall incidence of SSIs, just those caused by Staphylococcus aureus and methicillin-resistant S aureus (MRSA).16
Authors of 3 recent reviews have assessed the relationship between preoperative antiseptic washing and SSIs. Webster and Osborne analyzed 7 RCTs in a Cochrane review.17 All trials used 4% chlorhexidine gluconate as the antiseptic, and they included a total of 10,157 patients. The authors concluded that bathing with chlorhexidine did not significantly reduce SSIs compared with either placebo (RR, 0.91; 95% CI, 0.8–1.04) or bar soap (RR, 1.02; 95% CI, 0.57–1.84). Three additional studies in this review compared chlorhexidine bathing with no washing. One study showed a significant reduction of SSIs after the patients bathed with chlorhexidine (RR, 0.36; 95% CI, 0.17–0.79); the other 2 studies demonstrated no significant difference in outcome.
Kamel and colleagues conducted a recent systematic review that included 20 randomized and nonrandomized studies (n = 9,520); while the authors concluded that showering with an antiseptic solution reduced skin flora, they could not confirm that it produced a significant reduction in infection.18 Finally, in a meta-analysis that included 16 randomized and nonrandomized studies with 17,932 patients, Chlebicki and associates concluded that there was no significant reduction in SSIs with whole-body bathing with chlorhexidine compared with bathing with soap or placebo or with no bathing (RR, 0.90; 95% CI, 0.77–1.05; P = .19).19 A recent report from the World Health Organization confirmed these observations, although the report did not specifically focus on patients who had had a cesarean delivery.20
What the evidence says
Although chlorhexidine bathing reduces skin flora, especially in the number of staphylococcal species, this effect does not necessarily translate into a reduction of SSIs. Therefore, we recommend against routine chlorhexidine bathing before cesarean delivery, although we acknowledge that there is no apparent harm associated with this practice, assuming that the patient is not allergic to the medicated soap (Level II Evidence, Level C Recommendation; TABLE, page 2).
Did you read Part 1 of this series?
Preventing infection after cesarean delivery: Evidence-based guidance, Part 1
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
In part 1 of our review on preventing postcesarean infection, we critically evaluated methods of skin preparation and administration of prophylactic antibiotics. In part 2, we address preoperative cleansing of the vagina with an antiseptic solution, preoperative bathing with an antiseptic solution, methods of placental extraction, closure of the deep subcutaneous layer of the abdomen, and closure of the skin.
Related article:
Preventing infection after cesarean delivery: Evidence-based guidance
CASE: Should vaginal cleansing be performed prior to cesarean delivery?
An 18-year-old primigravid woman at 41 weeks’ gestation has been in labor for 16 hours, and now has an arrest of descent at 0 station. An intrauterine pressure catheter and scalp electrode have been in place for the same length of time. The patient has had 9 internal examinations during the period of membrane rupture. As you are preparing to scrub the patient’s abdomen, the third-year medical student asks, “When I was on the Gynecology Service, I saw the doctors wash the vagina with an antiseptic solution before they performed a vaginal hysterectomy. Should we also do that before we operate on this patient?”
Preoperative vaginal cleansing
A preoperative antiseptic vaginal scrub is often used as an additional step to help reduce postcesarean infection.
Does cleansing the vagina with povidone-iodine before surgery further reduce the risk of endometritis and wound infection?
Multiple studies have sought to determine if cleansing the vagina with an antiseptic solution further reduces the incidence of postcesarean infection beyond what can be achieved with systemic antibiotic prophylaxis. These studies typically have focused on 3 specific outcomes: endometritis, wound (surgical site) infection, and febrile morbidity. The term febrile morbidity is defined as a temperature ≥100.4°F (38°C) on any 2 postoperative days excluding the first 24 hours. However, many patients who meet the standard definition of febrile morbidity may not have a proven infection and will not require treatment with antibiotics. The more precise measures of outcome are distinctly symptomatic infections, such as endometritis and wound infection, although, as noted in the review of published studies below, some authors continue to use the term febrile morbidity as one measure of postoperative complications.
In a randomized, placebo-controlled trial (RCT) of 308 women having a nonemergent cesarean delivery, Starr and colleagues reported a decreased incidence of postoperative endometritis in women who received a 30-second vaginal scrub with povidone-iodine compared with women who received only an abdominal scrub (7.0% vs 14.5%, P<.05).1 The groups did not differ in the frequency of wound infection (0.7% vs 1.2%, P = .4) or febrile morbidity (23.9% vs 28.3%, P = .4).1
In another RCT, Haas and colleagues found that preoperative vaginal cleansing with povidone-iodine compared with an abdominal scrub alone was associated with a decreased incidence of a composite measure of postoperative morbidity (6.5% vs 11.7%; relative risk [RR], 0.55; 95% confidence interval [CI], 0.26–1.11; P = .11).2 The postoperative composite included fever, endometritis, sepsis, readmission, and wound infection.
Subsequently, Asghania and associates conducted a double-blind, nonrandomized study of 568 women having cesarean delivery who received an abdominal scrub plus a 30-second vaginal scrub with povidone-iodine or received an abdominal scrub alone.3 They documented a decreased incidence of postoperative endometritis in the women who received the combined scrub (1.4% vs 2.5%; P = .03, adjusted odds ratio [AOR], 0.03; 95% CI, 0.008–0.7). The authors observed no significant difference in febrile morbidity (4.9% vs 6.0%; P = .73) or wound infection (3.5% vs 3.2%; P = .5).3
Yildirim and colleagues conducted an RCT comparing rates of infection in 334 women who received an abdominal scrub plus vaginal cleansing with povidone-iodine and 336 patients who had only a standard abdominal scrub.4 They documented a decreased incidence of endometritis in women who received the vaginal scrub (6.9% vs 11.6%; P = .04; RR for infection in the control group, 1.69; 95% CI, 1.03–2.76.) The authors found no difference in febrile morbidity (16.5% vs 18.2%; P = .61) or wound infection (1.8% vs 2.7%; P = .60). Of note, in excluding from the analysis women who had ruptured membranes or who were in labor, the investigators found no differences in outcome, indicating that the greatest impact of vaginal cleansing was in the highest risk patients.
In 2014, Haas and associates published a Cochrane review evaluating the effectiveness of preoperative vaginal cleansing with povidone-iodine.5 The authors reviewed 7 studies that analyzed outcomes in 2,635 women. They concluded that vaginal preparation with povidone-iodine at the time of cesarean delivery significantly decreased postoperative endometritis when compared with the control group (4.3% vs 8.3%; RR, 0.45; 95% CI, 0.25–0.81). They also noted that the most profound impact of vaginal cleansing was in women who were in labor before delivery (7.4% vs 13.0%; RR, 0.56; 95% CI, 0.34–0.95) and in women with ruptured membranes at the time of delivery (4.3% vs 17.9%; RR, 0.24; 95% CI, 0.10–0.55). The authors did not find a significant difference in postoperative wound infection or frequency of fever in women who received the vaginal scrub.
Related article:
STOP using instruments to assist with delivery of the head at cesarean
A notable exception to the beneficial outcomes reported above was the study by Reid et al.6 These authors randomly assigned 247 women having cesarean delivery to an abdominal scrub plus vaginal scrub with povidone-iodine and assigned 251 women to only an abdominal scrub. The authors were unable to document any significant difference between the groups with respect to frequency of fever, endometritis, and wound infection.
Other methods of vaginal preparation also have been studied. For example, Pitt and colleagues conducted a double-blind RCT of 224 women having cesarean delivery and compared preoperative metronidazole vaginal gel with placebo.7 Most of the patients in this trial also received systemic antibiotic prophylaxis after the umbilical cord was clamped. The authors demonstrated a decreased incidence of postcesarean endometritis in women who received the intravaginal antibiotic gel (7% vs 17%; RR, 0.42; 95% CI, 0.19–0.92). There was no difference in febrile morbidity (13% vs 19%; P = .28) or wound infection (4% vs 3%, P = .50).
What the evidence says
Consider vaginal preparation with povidone-iodine at the time of cesarean delivery to reduce the risk of postpartum endometritis. Do not expect this intervention to significantly reduce the frequency of wound infection. Vaginal cleansing is of most benefit to women who have ruptured membranes or are in labor at the time of delivery (Level I Evidence, Level A Recommendation; TABLE). Whether vaginal preparation with chlorhexidine with 4% alcohol would have the same beneficial effect has not been studied in a systematic manner.
Placenta extraction, closure techniques
Evidence suggests that employing certain intraoperative approaches helps reduce the incidence of postcesarean infection.
What other measures help prevent infection following cesarean surgery?
One other measure known to decrease the risk of postcesarean endometritis is removing the placenta by exerting traction on the umbilical cord rather than extracting it manually. In one of the first descriptions of this intervention, Lasley and associates showed that, in high-risk patients who also received intravenous antibiotic prophylaxis after cord clamping, the rate of postoperative endometritis was 15% in the group that had spontaneous delivery of the placenta compared with 27% in women who had manual extraction (RR, 0.6; 95% CI, 0.3–0.9; P = .02).8 A recent Cochrane review that included multiple subsequent reports confirmed this observation (Level I Evidence, Level A Recommendation; TABLE, page 2).9
Abdominal wall closure. Two other interventions are valuable in decreasing the frequency of deep and superficial wound infection. In patients whose subcutaneous layer is >2 cm thick, closure of the deep subcutaneous tissue significantly reduces the risk of wound seroma, hematoma, and infection.10 In addition, closure of the skin edges with a subcuticular suture, as opposed to surgical staples, significantly reduces the frequency of superficial wound complications (Level I Evidence, Level A Recommendation; TABLE, page 2).11 Poliglecaprone 25, polyglactin 910, and polyglycolic acid suture, 3-0 or 4-0 gauge, are excellent suture choices for this closure.
Related article:
Does one particular cesarean technique confer better maternal and neonatal outcomes?
CASE
Planned cesarean delivery: Is preoperative antiseptic bathing warranted?
A 33-year-old woman (G2P1001) at 39 weeks’ gestation is scheduled for a repeat low transverse cesarean delivery. In addition to planning to implement the measures discussed above, her clinician is considering whether to recommend that the patient bathe with an antiseptic solution, such as chlorhexidine, the day before the procedure.
Preoperative antiseptic bathing
The concept of bathing with an antiseptic solution before surgery to prevent surgical site infections (SSIs) has been considered for many years. Intuitively, if the body’s resident and transient skin flora are decreased preoperatively with whole-body antiseptic washing, then the overall pathogen burden should be decreased and the risk of SSI also should be reduced. Historically, chlorhexidine preparations have been used as preoperative antiseptic solutions because they are so effective in reducing colony counts of skin flora, especially staphylococci.12 Although preoperative antiseptic washing definitely reduces the concentration of skin bacteria, the data regarding reduction in SSI are inconsistent. Of particular note, there are no studies investigating the impact of preoperative antiseptic bathing in women having cesarean delivery.
Does preop bathing with an antiseptic reduce infection risk?
One of the first studies evaluating preoperative antiseptic washing was published by Cruse and Foord in 1980.13 In this 10-year prospective investigation, the authors demonstrated that patients who underwent preoperative washing with a hexachlorophene solution had fewer SSIs compared with those who washed with a nonmedicated soap and those who did not wash at all. Subsequent studies by Brady et al in 1990,14 Wilcox et al in 2003,15 and Colling et al in 201516 all showed a decrease in the rate of SSIs with preoperative antiseptic washing, and the authors strongly supported this intervention. However, care must be taken when interpreting the results of these cohort investigations because in some cases antiseptic washing was not the only preoperative intervention. Thus, it is difficult to ascertain the true benefit of antiseptic washing alone.14,15 Moreover, in one study, preoperative antiseptic washing did not decrease the overall incidence of SSIs, just those caused by Staphylococcus aureus and methicillin-resistant S aureus (MRSA).16
Authors of 3 recent reviews have assessed the relationship between preoperative antiseptic washing and SSIs. Webster and Osborne analyzed 7 RCTs in a Cochrane review.17 All trials used 4% chlorhexidine gluconate as the antiseptic, and they included a total of 10,157 patients. The authors concluded that bathing with chlorhexidine did not significantly reduce SSIs compared with either placebo (RR, 0.91; 95% CI, 0.8–1.04) or bar soap (RR, 1.02; 95% CI, 0.57–1.84). Three additional studies in this review compared chlorhexidine bathing with no washing. One study showed a significant reduction of SSIs after the patients bathed with chlorhexidine (RR, 0.36; 95% CI, 0.17–0.79); the other 2 studies demonstrated no significant difference in outcome.
Kamel and colleagues conducted a recent systematic review that included 20 randomized and nonrandomized studies (n = 9,520); while the authors concluded that showering with an antiseptic solution reduced skin flora, they could not confirm that it produced a significant reduction in infection.18 Finally, in a meta-analysis that included 16 randomized and nonrandomized studies with 17,932 patients, Chlebicki and associates concluded that there was no significant reduction in SSIs with whole-body bathing with chlorhexidine compared with bathing with soap or placebo or with no bathing (RR, 0.90; 95% CI, 0.77–1.05; P = .19).19 A recent report from the World Health Organization confirmed these observations, although the report did not specifically focus on patients who had had a cesarean delivery.20
What the evidence says
Although chlorhexidine bathing reduces skin flora, especially in the number of staphylococcal species, this effect does not necessarily translate into a reduction of SSIs. Therefore, we recommend against routine chlorhexidine bathing before cesarean delivery, although we acknowledge that there is no apparent harm associated with this practice, assuming that the patient is not allergic to the medicated soap (Level II Evidence, Level C Recommendation; TABLE, page 2).
Did you read Part 1 of this series?
Preventing infection after cesarean delivery: Evidence-based guidance, Part 1
Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
- Starr RV, Zurawski J, Ismail M. Preoperative vaginal preparation with povidone-iodine and the risk of postcesarean endometritis. Obstet Gynecol. 2005;105(5 pt 1):1024–1029.
- Haas DM, Pazouki F, Smith RR, et al. Vaginal cleansing before cesarean delivery to reduce postoperative infectious morbidity: a randomized controlled trial. Am J Obstet Gynecol. 2010;202(3):310.e1–e6.
- Asghania M, Mirblouk F, Shakiba M, Faraji R. Preoperative vaginal preparation with povidone-iodine on post-caesarean infectious morbidity. J Obstet Gynaecol. 2011;31(5):400–403.
- Yildirim G, Güngördük K, Asicioglu O, et al. Does vaginal preparation with povidone-iodine prior to caesarean delivery reduce the risk of endometritis? A randomized controlled trial. J Matern Fetal Neonatal Med. 2012;25(11):2316–2321.
- Haas DM, Morgan S, Contreras K. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Sys Rev. 2014;(12):CD007892.
- Reid VC, Hartmann KE, McMahon M, Fry EP. Vaginal preparation with povidone iodine and postcesarean infectious morbidity: a randomized controlled trial. Obstet Gynecol. 2001;97(1):147–152.
- Pitt C, Sanchez-Ramos L, Kaunitz AM. Adjunctive intravaginal metronidazole for the prevention of postcesarean endometritis: a randomized controlled trial. Obstet Gynecol. 2001;98(5 pt 1):745–750.
- Lasley DS, Eblen A, Yancey MK, Duff P. The effect of placental removal method on the incidence of postcesarean infections. Am J Obstet Gynecol. 1997;176(6):1250–1254.
- Methods of delivering the placenta at caesarean section [comment]. Obstet Gynecol. 2008;112(5):1173–1174.
- Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 pt 1):974–980.
- Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a metaanalysis. Am J Obstet Gynecol. 2015;212(5):621.e1–e10.
- , , , . Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers . Ann Thorac Surg. 1988 ; 45(1) : 35 –3 8 .
- , . The epidemiology of wound infection. A 10-year prospective study of 62,939 wounds . Surg Clin North Am. 1980 ; 60 ( 1 ): 27 – 40 .
- , , , Harkness JL. Successful control of endemic MRSA in a cardiothoracic surgical unit . Med J Aust. 1990 ; 152(5) : 240 –24 5 .
- , , , et al. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J Hosp Infect. 2003 ; 54(3) : 196 – 201 .
- , , , Banton K, Bellman G. Pre-operative antiseptic shower and bath policy decreases the rate of S aureus and methicillin-resistant S aureus surgical site infections in patients undergoing joint arthroplasty . Surg Infect. 2015 ; 16(2):124–132.
- Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. 2012;(9):CD004985.
- , , , Mierzwinski-Urban M, Embil JM. Preoperative skin antiseptic preparations for preventing surgical site infections: a systematic review . Infect Control Hosp Epidemiol. 2012 ; 33(6) : 608 – 617 .
- , , , Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis . Am J Infect Control. 2013 ; 41(2) : 167 –1 73 .
- Global guidelines for the prevention of surgical site infection. Geneva, Switzerland: World Health Organization; November 2016. http://www.who.int/gpsc/global-guidelines-web.pdf?ua=1. Accessed November 9, 2016.
- Starr RV, Zurawski J, Ismail M. Preoperative vaginal preparation with povidone-iodine and the risk of postcesarean endometritis. Obstet Gynecol. 2005;105(5 pt 1):1024–1029.
- Haas DM, Pazouki F, Smith RR, et al. Vaginal cleansing before cesarean delivery to reduce postoperative infectious morbidity: a randomized controlled trial. Am J Obstet Gynecol. 2010;202(3):310.e1–e6.
- Asghania M, Mirblouk F, Shakiba M, Faraji R. Preoperative vaginal preparation with povidone-iodine on post-caesarean infectious morbidity. J Obstet Gynaecol. 2011;31(5):400–403.
- Yildirim G, Güngördük K, Asicioglu O, et al. Does vaginal preparation with povidone-iodine prior to caesarean delivery reduce the risk of endometritis? A randomized controlled trial. J Matern Fetal Neonatal Med. 2012;25(11):2316–2321.
- Haas DM, Morgan S, Contreras K. Vaginal preparation with antiseptic solution before cesarean section for preventing postoperative infections. Cochrane Database Sys Rev. 2014;(12):CD007892.
- Reid VC, Hartmann KE, McMahon M, Fry EP. Vaginal preparation with povidone iodine and postcesarean infectious morbidity: a randomized controlled trial. Obstet Gynecol. 2001;97(1):147–152.
- Pitt C, Sanchez-Ramos L, Kaunitz AM. Adjunctive intravaginal metronidazole for the prevention of postcesarean endometritis: a randomized controlled trial. Obstet Gynecol. 2001;98(5 pt 1):745–750.
- Lasley DS, Eblen A, Yancey MK, Duff P. The effect of placental removal method on the incidence of postcesarean infections. Am J Obstet Gynecol. 1997;176(6):1250–1254.
- Methods of delivering the placenta at caesarean section [comment]. Obstet Gynecol. 2008;112(5):1173–1174.
- Chelmow D, Rodriguez EJ, Sabatini MM. Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis. Obstet Gynecol. 2004;103(5 pt 1):974–980.
- Mackeen AD, Schuster M, Berghella V. Suture versus staples for skin closure after cesarean: a metaanalysis. Am J Obstet Gynecol. 2015;212(5):621.e1–e10.
- , , , . Influence of preoperative showers on staphylococcal skin colonization: a comparative trial of antiseptic skin cleansers . Ann Thorac Surg. 1988 ; 45(1) : 35 –3 8 .
- , . The epidemiology of wound infection. A 10-year prospective study of 62,939 wounds . Surg Clin North Am. 1980 ; 60 ( 1 ): 27 – 40 .
- , , , Harkness JL. Successful control of endemic MRSA in a cardiothoracic surgical unit . Med J Aust. 1990 ; 152(5) : 240 –24 5 .
- , , , et al. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J Hosp Infect. 2003 ; 54(3) : 196 – 201 .
- , , , Banton K, Bellman G. Pre-operative antiseptic shower and bath policy decreases the rate of S aureus and methicillin-resistant S aureus surgical site infections in patients undergoing joint arthroplasty . Surg Infect. 2015 ; 16(2):124–132.
- Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. 2012;(9):CD004985.
- , , , Mierzwinski-Urban M, Embil JM. Preoperative skin antiseptic preparations for preventing surgical site infections: a systematic review . Infect Control Hosp Epidemiol. 2012 ; 33(6) : 608 – 617 .
- , , , Maki DG. Preoperative chlorhexidine shower or bath for prevention of surgical site infection: a meta-analysis . Am J Infect Control. 2013 ; 41(2) : 167 –1 73 .
- Global guidelines for the prevention of surgical site infection. Geneva, Switzerland: World Health Organization; November 2016. http://www.who.int/gpsc/global-guidelines-web.pdf?ua=1. Accessed November 9, 2016.
