Osteoporosis

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

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The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

[email protected]

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

An accelerated path to surgery after hip fracture did not improve mortality or major complications, according to a new international randomized trial. However, a fast track to surgery hastened mobilization, weight-bearing, and hospital discharge, and reduced the risk of urinary tract infection and delirium.

The HIP ATTACK (Hip Fracture Accelerated Surgical Treatment and Care Track) study enrolled 2,970 patients (median age, 79 years; 69% women) during March 2014-May 2019. The study excluded patients younger than 45 years, as well as those who were on nonreversible anticoagulation and who had high-energy or more complex hip fractures. In all, 1,487 patients were randomly assigned to the accelerated-surgery group, which received early medical evaluation with a goal of heading to surgery within 6 hours of a hip fracture diagnosis. The goal was achieved, with patients in the intervention arm receiving care at a median 6 hours after diagnosis. Patients in the 69 participating hospitals in 17 countries who were assigned to standard of care received surgery at a median 24 hours after diagnosis (P less than .001).

“Observational data, clinical experience, and biological rationale suggest that the longer a patient is immobile and lying in a bed, the higher the risk of poor outcomes,” wrote principal investigators Philip J. Devereaux, MD, PhD, and Mohit Bhandari, MD, PhD, of McMaster University, Hamilton, Ont., and their colleagues on the HIP ATTACK writing committee.

The study was the first large, randomized trial that directly compared accelerated surgery with standard of care, noted the authors. Previous observational studies had shown worse outcomes for those usual-care patients who waited longer for surgery.

In HIP ATTACK, there was no difference in the primary outcome measures of 90-day mortality and major complications for patients receiving surgery within 6 hours after hip fracture diagnosis, compared with those who received surgery within 24 hours. The coprimary outcome measures included serious complications, such as MI, stroke, venous thromboembolism, sepsis, pneumonia, and life-threatening or major bleeding.

In practice, the researchers found that patients in the accelerated-surgery group received medical clearance in a median time of 2 hours after a diagnosis of hip fracture, whereas the standard of care group was cleared in 4 hours.

At 90 days, 9% of patients in the accelerated-surgery group and 10% of those in the usual-care group had died, a nonsignificant difference between the two groups. In both groups, 22% of patients experienced a major complication. A post hoc analysis that looked for any site-clustering effects did not detect different outcomes, the investigators wrote.

Delirium occurred in 132 patients (9%) of the accelerated-surgery group and in 175 patients (12%) in the usual-care group (odds ratio, 0.72; 95% confidence interval, 0.58-0.92). Infection without sepsis and urinary tract infection were both less common in the accelerated-surgery group (hazard ratio, 0.80 and 0.78, respectively).

The authors noted that the potential benefits of a speedy course to surgery, including reduced immobility and less pain, could be negated if physicians had less time to optimize medical care for older patients with multiple comorbidities and who make up a significant proportion of those who sustain low-energy hip fractures. However, medical complications, such as MI and new-onset atrial fibrillation, were not seen more frequently in the accelerated-surgery group.

In an editorial accompanying the study, Alejandro Lizaur-Utrilla, MD, and Fernando Lopez-Prats, MD, of the Universidad Miguel Hernández, Alicante, Spain, observed that the 6-hour window for hip fracture surgery may be difficult to achieve given clinical practicalities and that, in some cases, the 6-hour window might be unavoidable if severe comorbidities and overall poor health make early surgery inadvisable.

They also expressed concern that, despite the lack of harm shown in the patients who underwent accelerated surgery, the surgery “might negatively affect patients’ outcomes by preventing or limiting the opportunity for optimization of patients’ medical conditions before surgery.” They called for further study to delineate how fitness for surgery affects outcomes in accelerated surgery and to further examine whether the better outcomes are associated with improved cost-effectiveness.

Multiple HIP ATTACK coinvestigators reported relationships with pharmaceutical and medical device companies, including companies that manufacture hip prosthesis and orthopedic surgical devices and implants. The study was sponsored by the Canadian Population Health Research Institute, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, Physicians’ Services Incorporated Foundation, Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding.

SOURCE: Borges F et al. Lancet. 2020 Feb. 9. doi: 10.1016/S0140-6736(20)30058-1.


 

Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.

Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.

In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.

At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.

All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.

The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.

A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”

The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.

SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.

Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.

Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.

In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.

At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.

All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.

The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.

A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”

The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.

SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.

Women with osteoporosis who received a single infusion of zoledronate after discontinuing denosumab (Prolia) maintained bone mineral density at both the lumbar spine and the total hip, based on data from 120 individuals.

Although denosumab is often prescribed for postmenopausal osteoporosis, its effects disappear when treatment ends, wrote Judith Everts-Graber, MD, of OsteoRheuma Bern (Switzerland), and colleagues. In addition, recent reports of increased fractures in osteoporotic women after denosumab discontinuation highlight the need for subsequent therapy, but no protocol has been established.

In a study published in the Journal of Bone and Mineral Research, the investigators reviewed data from women aged older than 48 years with postmenopausal osteoporosis who were treated with denosumab between Aug. 1, 2010, and March 31, 2019. The women received four or more injections of 60 mg denosumab administered at 6-month intervals, followed by a single infusion of 5 mg zoledronate 6 months after the final denosumab injection. Patients were evaluated using dual-energy x-ray absorptiometry and vertebral fracture assessment every 2 years after starting denosumab; the average duration of treatment was 3 years.

At an average of 2.5 years after discontinuing denosumab, women who received zoledronate retained 66% of bone mineral density (BMD) gains at the lumbar spine, 49% at the total hip, and 57% at the femoral neck. In addition, three patients developed symptomatic single vertebral fractures and four patients developed peripheral fractures between 1 and 3 years after their last denosumab injections, but none of these patients sustained multiple fractures.

All bone loss occurred within 18 months of denosumab discontinuation, and no significant differences appeared between patients with gains in BMD greater than or less than 9%.

The study findings were limited by several factors, including the retrospective design and the lack of a control group, the researchers noted. However, they collected data from 11 of 28 patients who did not follow the treatment recommendations and did not receive zoledronate after discontinuing denosumab. “As expected, BMD of the lumbar spine and total hip decreased to baseline,” they wrote. In addition, 2 of the 11 patients experienced multiple vertebral fractures.

A single 5-mg infusion of zoledronate “may be a promising step in identifying sequential long-term treatment strategies for osteoporosis,” the researchers concluded. “Nevertheless, each patient requires an individualized surveillance and treatment plan after denosumab discontinuation, including BMD assessment, evaluation of bone turnover markers and consideration of individual clinical risk factors, in particular prevalent fragility fractures.”

The study was funded by OsteoRheuma Bern. The researchers reported having no financial conflicts.

SOURCE: Everts-Graber J et al. J Bone Miner Res. 2020 Jan 28. doi: 10.1002/jbmr.3962.

A new study has reinforced the link between anorexia nervosa and reduced bone mineral density (BMD), especially in patients with lower body mass index.

“Our large study raises further concerns that [anorexia nervosa] has significant deleterious effects on BMD,” wrote Cassandra Workman, MD, of the Eating Recovery Center in Denver and coauthors. The study was published in Bone.

To determine the degree of low BMD in patients with certain severe eating disorders, the researchers reviewed the medical records of 336 patients with either anorexia nervosa–restricting subtype (AN-R) or anorexia nervosa–binge/purge subtype (AN-BP) who had been admitted to a treatment facility in Denver. Bone density was assessed using dual-energy x-ray absorptiometry, with osteopenia being diagnosed for an average BMD z score between –1.0 and –2.0 and osteoporosis being diagnosed for an average BMD z score of less than –2.0. The average age of the patients was 27 years (standard deviation, 9.12; range, 18-69), and 91% (n = 305) were women.

Across the sample, the average BMD z score was –1.67 (SD, 1.21), and 43.5% of the sample met the established criteria for low BMD.

Patients with AN-R had slightly lower z scores (–1.79; SD, 1.31), compared with patients with AN-BP (–1.54; SD, 1.08; P = .06), but the severity of osteoporosis was greater in patients with AN-R, compared with patients with AN-BP (chi-square, 7.40; P less than .01). Lower body mass index topped both anorexia nervosa subtype and duration of illness as a predictor of low BMD and probable osteoporosis (P less than .001).

The authors acknowledged their study’s limitations, including the use of retrospective data from the patient charts, which did not allow for assessment of follow-up improvements or longer-term effects. In addition, they noted that extrapolation of their findings may be problematic because all the patients were from a single site and the data might be representative of “a more ill population than a true cross section of the eating disorder population.”

The authors reported no conflicts of interest.

SOURCE: Workman C et al. Bone. 2019 Nov 23. doi: 10.1016/j.bone.2019.115161.

A new study has reinforced the link between anorexia nervosa and reduced bone mineral density (BMD), especially in patients with lower body mass index.

“Our large study raises further concerns that [anorexia nervosa] has significant deleterious effects on BMD,” wrote Cassandra Workman, MD, of the Eating Recovery Center in Denver and coauthors. The study was published in Bone.

To determine the degree of low BMD in patients with certain severe eating disorders, the researchers reviewed the medical records of 336 patients with either anorexia nervosa–restricting subtype (AN-R) or anorexia nervosa–binge/purge subtype (AN-BP) who had been admitted to a treatment facility in Denver. Bone density was assessed using dual-energy x-ray absorptiometry, with osteopenia being diagnosed for an average BMD z score between –1.0 and –2.0 and osteoporosis being diagnosed for an average BMD z score of less than –2.0. The average age of the patients was 27 years (standard deviation, 9.12; range, 18-69), and 91% (n = 305) were women.

Across the sample, the average BMD z score was –1.67 (SD, 1.21), and 43.5% of the sample met the established criteria for low BMD.

Patients with AN-R had slightly lower z scores (–1.79; SD, 1.31), compared with patients with AN-BP (–1.54; SD, 1.08; P = .06), but the severity of osteoporosis was greater in patients with AN-R, compared with patients with AN-BP (chi-square, 7.40; P less than .01). Lower body mass index topped both anorexia nervosa subtype and duration of illness as a predictor of low BMD and probable osteoporosis (P less than .001).

The authors acknowledged their study’s limitations, including the use of retrospective data from the patient charts, which did not allow for assessment of follow-up improvements or longer-term effects. In addition, they noted that extrapolation of their findings may be problematic because all the patients were from a single site and the data might be representative of “a more ill population than a true cross section of the eating disorder population.”

The authors reported no conflicts of interest.

SOURCE: Workman C et al. Bone. 2019 Nov 23. doi: 10.1016/j.bone.2019.115161.

A new study has reinforced the link between anorexia nervosa and reduced bone mineral density (BMD), especially in patients with lower body mass index.

“Our large study raises further concerns that [anorexia nervosa] has significant deleterious effects on BMD,” wrote Cassandra Workman, MD, of the Eating Recovery Center in Denver and coauthors. The study was published in Bone.

To determine the degree of low BMD in patients with certain severe eating disorders, the researchers reviewed the medical records of 336 patients with either anorexia nervosa–restricting subtype (AN-R) or anorexia nervosa–binge/purge subtype (AN-BP) who had been admitted to a treatment facility in Denver. Bone density was assessed using dual-energy x-ray absorptiometry, with osteopenia being diagnosed for an average BMD z score between –1.0 and –2.0 and osteoporosis being diagnosed for an average BMD z score of less than –2.0. The average age of the patients was 27 years (standard deviation, 9.12; range, 18-69), and 91% (n = 305) were women.

Across the sample, the average BMD z score was –1.67 (SD, 1.21), and 43.5% of the sample met the established criteria for low BMD.

Patients with AN-R had slightly lower z scores (–1.79; SD, 1.31), compared with patients with AN-BP (–1.54; SD, 1.08; P = .06), but the severity of osteoporosis was greater in patients with AN-R, compared with patients with AN-BP (chi-square, 7.40; P less than .01). Lower body mass index topped both anorexia nervosa subtype and duration of illness as a predictor of low BMD and probable osteoporosis (P less than .001).

The authors acknowledged their study’s limitations, including the use of retrospective data from the patient charts, which did not allow for assessment of follow-up improvements or longer-term effects. In addition, they noted that extrapolation of their findings may be problematic because all the patients were from a single site and the data might be representative of “a more ill population than a true cross section of the eating disorder population.”

The authors reported no conflicts of interest.

SOURCE: Workman C et al. Bone. 2019 Nov 23. doi: 10.1016/j.bone.2019.115161.

MADRID – Adults with atopic dermatitis (AD) face significantly increased risks of osteoporosis and major osteoporotic fractures – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.

Bruce Jancin/MDedge News

A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.

His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”

He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.

Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.

In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.

In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H₂ receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.

Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.

In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.

A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.

“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.

A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.

“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.

Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.

[email protected]

MADRID – Adults with atopic dermatitis (AD) face significantly increased risks of osteoporosis and major osteoporotic fractures – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.

Bruce Jancin/MDedge News

A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.

His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”

He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.

Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.

In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.

In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H₂ receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.

Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.

In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.

A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.

“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.

A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.

“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.

Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.

[email protected]

MADRID – Adults with atopic dermatitis (AD) face significantly increased risks of osteoporosis and major osteoporotic fractures – even if they’ve never taken systemic corticosteroids, according to a large observational Danish national registry study.

Bruce Jancin/MDedge News

A key study finding was that these elevated risks were concentrated in the patients who used potent or superpotent topical corticosteroids. Adult AD patients who used mild- or moderate-potency topical steroids were not at significantly increased risk. Neither were patients on topical calcineurin inhibitors, Jacob P. Thyssen, MD, PhD, reported at a meeting of the European Task Force on Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology.

“The absolute risk is low, but it’s real,” commented Dr. Thyssen, professor of dermatology at the University of Copenhagen.

His advice to colleagues: “Dermatologists should consider alternative treatments in the chronic excessive users of topical corticosteroids, or use them in combination with prophylactic treatment to preserve bone homeostasis in such patients.”

He presented the results of a retrospective case-control study of 10,636 Danish adults with AD and 87,989 matched controls. At baseline in this study, which featured a maximum of 20 years of follow-up starting in 1997, participants had no history of osteoporosis.

Dr. Thyssen expressed the absolute risk of being diagnosed with osteoporosis in the study as follows: If 10,000 adult AD patients were followed for 1 year, on average 23.5 of them would be diagnosed with osteoporosis, a rate more than double the 10.3 per 10,000 in the general population. Moreover, on average, 42.6 out of 10,000 adult AD patients would incur a major osteoporotic fracture during a year of follow-up, compared with 32.3 individuals in the general population.

In the subgroup of patients who never used systemic corticosteroids, the risk of being diagnosed with osteoporosis was 12.8 per 10,000 per year, significantly higher than the 7.4 per 10,000 rate in the general population. Similarly, the 1-year rate of major osteoporotic fractures was 33.1 per 10,000 among the AD group and 29.6 in matched controls.

In a Cox regression analysis adjusted for age, sex, socioeconomic status, body mass index, asthma, and the use of a variety of medications thought to potentially have a negative effect upon bone metabolism, the risk of osteoporosis in the entire group of 10,636 adult AD patients was 51% greater than in matched controls, and their risk of major osteoporotic fractures was 18% greater. In the subgroup of AD patients who never used systemic steroids, the risks of osteoporosis and major osteoporotic fractures were 82% and 14% greater than in controls. The medications adjusted for in the regression analysis included proton pump inhibitors, thiazide diuretics, H₂ receptor blockers, statins, cyclosporine, hormone therapy, contraceptives, and psychotropic medications.

Scoring Atopic Dermatitis (SCORAD) ratings were available on roughly 4,000 of the adult AD patients. In an analysis of this large subgroup, disease severity as reflected in SCORAD scores did not explain the increased osteoporosis and fracture risks. However, the use of potent or superpotent topical corticosteroids did. Patients who used potent topical steroids had a statistically significant 16% increased risk of being diagnosed with osteoporosis than nonusers, as well as a 7% increased risk of major osteoporotic fractures. Patients who applied superpotent topical steroids had 42% and 18% increased risks of those two adverse outcomes.

In contrast, neither the use of topical calcineurin inhibitors nor mild- or mid-potency topical steroids was associated with increased risk of bone events in a Cox regression analysis adjusted for potential confounders.

A relationship between the use of high-potency topical corticosteroids and adverse bone events is biologically plausible, according to Dr. Thyssen. He and his coinvestigators have previously documented a 100%-400% increased rate of chemical penetration through atopic skin, which is notoriously barrier damaged.

“We find it very likely that, if you put topical steroids on atopic skin in high amounts and for a very long time, you may have systemic effects,” he said.

A great many adult AD patients do exactly that. When Dr. Thyssen and coworkers analyzed Danish national prescription drug registry data for their patient cohort, they found that roughly one-third of the elderly subgroup had filled prescriptions totaling greater than 2 kg of mometasone or other similar-potency steroids over the previous 10 years.

“So we know that a significant proportion of our atopic dermatitis patients are really high users of topical corticosteroids,” the dermatologist noted.

Dr. Thyssen’s national osteoporosis and fracture study was funded with a government research grant. He reported serving as an advisor to and/or recipient of research grants from AbbVie, Pfizer, Leo Pharma, Eli Lilly, Regeneron, Sanofi Genzyme, and Union Therapeutics.

[email protected]

Vitamin D supplementation alone does not appear to reduce the risk of fracture, but a combination of vitamin D and calcium may, according to a systematic review and meta-analysis published in JAMA Network Open.

Pang Yao, PhD, from the Nuffield Department of Population Health at the University of Oxford (England) and coauthors wrote that, while randomized, controlled trials (RCTs) of vitamin D supplements – either alone or in combination with calcium supplementation – have found conflicting results, most only had limited power to detect differences in the risk of fracture.

Dr. Yao and associates performed a meta-analysis of 11 observational studies with 39,141 participants, 11 RCTs of vitamin D supplementation alone in 34,243 participants, and 6 RCTs of calcium plus vitamin D involving 49,282 participants.

The analysis of the observational studies revealed that each 10.0-ng/mL increase in blood 25-hydroxyvitamin D concentrations was associated with a 7% lower risk of any fracture. However the authors noted significant heterogeneity between individual studies.

The meta-analysis of the 11 trials of vitamin D alone found that supplementation was not associated with significant change in the risk for any fracture or for hip fracture. Even subgroup analyses looking at age, residential status, location, study design, daily supplementation, or duration of supplementation failed to find any effect. However, there was a median difference in blood 25-hydroxyvitamin D concentrations of 8.4 ng/mL with vitamin D supplementation.

In the meta-analysis of the six vitamin D plus calcium trials, there was a significant 6% reduction in the rate of any fracture and a 16% reduction in hip fracture rate with supplementation. Overall, there was a 1% reduction in the risk of any fracture for each 0.4-ng/mL difference in blood 25-hydroxyvitamin D concentration and 2% reduction in the risk of hip fracture.

However, the authors judged five of those six vitamin D plus calcium trials to be at high risk of bias, with two having open-label designs, although there was little heterogeneity among the studies. All the trials used either 800 or 400 IU/day of vitamin D and 1,200 or 800 mg/day of calcium, and the mean duration of treatment was 5.9 years.

Participants aged 80 years or older living in institutions showed greater reductions in the risk of any fracture with calcium plus vitamin D supplementation, compared with those younger than 80 years who were living in the community.

“In this systematic review and meta-analysis, the available evidence from completed RCTs provided no support for the effects of vitamin D alone on prevention of fracture, but most of these RCTs were constrained by methodological problems,” they wrote. “Meta-analyses of ongoing RCTs assessing the effects of higher daily doses of vitamin D on fracture risk are needed before making recommendations on the use of vitamin D for prevention of fracture.”

One author was supported by a Sino-British Fellowship Trust scholarship, and another received grants from the U.K. Medical Research Council. No conflicts of interest were declared.

SOURCE: Yao P et al. JAMA Netw Open. 2019. doi: 10.1001/jamanetworkopen.2019.17789.

Vitamin D supplementation alone does not appear to reduce the risk of fracture, but a combination of vitamin D and calcium may, according to a systematic review and meta-analysis published in JAMA Network Open.

Pang Yao, PhD, from the Nuffield Department of Population Health at the University of Oxford (England) and coauthors wrote that, while randomized, controlled trials (RCTs) of vitamin D supplements – either alone or in combination with calcium supplementation – have found conflicting results, most only had limited power to detect differences in the risk of fracture.

Dr. Yao and associates performed a meta-analysis of 11 observational studies with 39,141 participants, 11 RCTs of vitamin D supplementation alone in 34,243 participants, and 6 RCTs of calcium plus vitamin D involving 49,282 participants.

The analysis of the observational studies revealed that each 10.0-ng/mL increase in blood 25-hydroxyvitamin D concentrations was associated with a 7% lower risk of any fracture. However the authors noted significant heterogeneity between individual studies.

The meta-analysis of the 11 trials of vitamin D alone found that supplementation was not associated with significant change in the risk for any fracture or for hip fracture. Even subgroup analyses looking at age, residential status, location, study design, daily supplementation, or duration of supplementation failed to find any effect. However, there was a median difference in blood 25-hydroxyvitamin D concentrations of 8.4 ng/mL with vitamin D supplementation.

In the meta-analysis of the six vitamin D plus calcium trials, there was a significant 6% reduction in the rate of any fracture and a 16% reduction in hip fracture rate with supplementation. Overall, there was a 1% reduction in the risk of any fracture for each 0.4-ng/mL difference in blood 25-hydroxyvitamin D concentration and 2% reduction in the risk of hip fracture.

However, the authors judged five of those six vitamin D plus calcium trials to be at high risk of bias, with two having open-label designs, although there was little heterogeneity among the studies. All the trials used either 800 or 400 IU/day of vitamin D and 1,200 or 800 mg/day of calcium, and the mean duration of treatment was 5.9 years.

Participants aged 80 years or older living in institutions showed greater reductions in the risk of any fracture with calcium plus vitamin D supplementation, compared with those younger than 80 years who were living in the community.

“In this systematic review and meta-analysis, the available evidence from completed RCTs provided no support for the effects of vitamin D alone on prevention of fracture, but most of these RCTs were constrained by methodological problems,” they wrote. “Meta-analyses of ongoing RCTs assessing the effects of higher daily doses of vitamin D on fracture risk are needed before making recommendations on the use of vitamin D for prevention of fracture.”

One author was supported by a Sino-British Fellowship Trust scholarship, and another received grants from the U.K. Medical Research Council. No conflicts of interest were declared.

SOURCE: Yao P et al. JAMA Netw Open. 2019. doi: 10.1001/jamanetworkopen.2019.17789.

Vitamin D supplementation alone does not appear to reduce the risk of fracture, but a combination of vitamin D and calcium may, according to a systematic review and meta-analysis published in JAMA Network Open.

Pang Yao, PhD, from the Nuffield Department of Population Health at the University of Oxford (England) and coauthors wrote that, while randomized, controlled trials (RCTs) of vitamin D supplements – either alone or in combination with calcium supplementation – have found conflicting results, most only had limited power to detect differences in the risk of fracture.

Dr. Yao and associates performed a meta-analysis of 11 observational studies with 39,141 participants, 11 RCTs of vitamin D supplementation alone in 34,243 participants, and 6 RCTs of calcium plus vitamin D involving 49,282 participants.

The analysis of the observational studies revealed that each 10.0-ng/mL increase in blood 25-hydroxyvitamin D concentrations was associated with a 7% lower risk of any fracture. However the authors noted significant heterogeneity between individual studies.

The meta-analysis of the 11 trials of vitamin D alone found that supplementation was not associated with significant change in the risk for any fracture or for hip fracture. Even subgroup analyses looking at age, residential status, location, study design, daily supplementation, or duration of supplementation failed to find any effect. However, there was a median difference in blood 25-hydroxyvitamin D concentrations of 8.4 ng/mL with vitamin D supplementation.

In the meta-analysis of the six vitamin D plus calcium trials, there was a significant 6% reduction in the rate of any fracture and a 16% reduction in hip fracture rate with supplementation. Overall, there was a 1% reduction in the risk of any fracture for each 0.4-ng/mL difference in blood 25-hydroxyvitamin D concentration and 2% reduction in the risk of hip fracture.

However, the authors judged five of those six vitamin D plus calcium trials to be at high risk of bias, with two having open-label designs, although there was little heterogeneity among the studies. All the trials used either 800 or 400 IU/day of vitamin D and 1,200 or 800 mg/day of calcium, and the mean duration of treatment was 5.9 years.

Participants aged 80 years or older living in institutions showed greater reductions in the risk of any fracture with calcium plus vitamin D supplementation, compared with those younger than 80 years who were living in the community.

“In this systematic review and meta-analysis, the available evidence from completed RCTs provided no support for the effects of vitamin D alone on prevention of fracture, but most of these RCTs were constrained by methodological problems,” they wrote. “Meta-analyses of ongoing RCTs assessing the effects of higher daily doses of vitamin D on fracture risk are needed before making recommendations on the use of vitamin D for prevention of fracture.”

One author was supported by a Sino-British Fellowship Trust scholarship, and another received grants from the U.K. Medical Research Council. No conflicts of interest were declared.

SOURCE: Yao P et al. JAMA Netw Open. 2019. doi: 10.1001/jamanetworkopen.2019.17789.

Several studies published over the last few years have shown declining rates of diagnosis and treatment of osteoporosis in older adults. In part, this may be due to declining ability to diagnose osteoporosis because declining reimbursement for dual x-ray absorptiometry has made it less available to patients and doctors. The study by Curtis et al. from the annual meeting of the American College of Rheumatology confirms prior findings and confirmation is important in driving the message home.

More research is needed to understand the reasons why patients and health care providers are not diagnosing osteoporosis, given that we can easily do so, and not treating osteoporosis or accepting recommended treatments for osteoporosis, given that we have many effective treatments that reduce the risk of fractures, many of them very inexpensive.

The vast majority of Medicare patients have major risk factors for falls, and falls are the most important risk factor for osteoporotic fractures. It is important to be proactive, to ask about drugs and diseases than increase falls, to educate patients about how to prevent falls, and to initiate treatments that strengthen bones so that they are less likely to break as a consequence of falling.

Dr. Shane is an endocrinologist, professor of medicine, and vice chair of medicine for clinical and epidemiological research at Columbia University in New York. She had no conflicts to disclose.

Several studies published over the last few years have shown declining rates of diagnosis and treatment of osteoporosis in older adults. In part, this may be due to declining ability to diagnose osteoporosis because declining reimbursement for dual x-ray absorptiometry has made it less available to patients and doctors. The study by Curtis et al. from the annual meeting of the American College of Rheumatology confirms prior findings and confirmation is important in driving the message home.

More research is needed to understand the reasons why patients and health care providers are not diagnosing osteoporosis, given that we can easily do so, and not treating osteoporosis or accepting recommended treatments for osteoporosis, given that we have many effective treatments that reduce the risk of fractures, many of them very inexpensive.

The vast majority of Medicare patients have major risk factors for falls, and falls are the most important risk factor for osteoporotic fractures. It is important to be proactive, to ask about drugs and diseases than increase falls, to educate patients about how to prevent falls, and to initiate treatments that strengthen bones so that they are less likely to break as a consequence of falling.

Dr. Shane is an endocrinologist, professor of medicine, and vice chair of medicine for clinical and epidemiological research at Columbia University in New York. She had no conflicts to disclose.

Several studies published over the last few years have shown declining rates of diagnosis and treatment of osteoporosis in older adults. In part, this may be due to declining ability to diagnose osteoporosis because declining reimbursement for dual x-ray absorptiometry has made it less available to patients and doctors. The study by Curtis et al. from the annual meeting of the American College of Rheumatology confirms prior findings and confirmation is important in driving the message home.

More research is needed to understand the reasons why patients and health care providers are not diagnosing osteoporosis, given that we can easily do so, and not treating osteoporosis or accepting recommended treatments for osteoporosis, given that we have many effective treatments that reduce the risk of fractures, many of them very inexpensive.

The vast majority of Medicare patients have major risk factors for falls, and falls are the most important risk factor for osteoporotic fractures. It is important to be proactive, to ask about drugs and diseases than increase falls, to educate patients about how to prevent falls, and to initiate treatments that strengthen bones so that they are less likely to break as a consequence of falling.

Dr. Shane is an endocrinologist, professor of medicine, and vice chair of medicine for clinical and epidemiological research at Columbia University in New York. She had no conflicts to disclose.

Treatment of osteoporosis in older adults at increased risk for fractures declined from 2010 to 2014, based on a study of nearly 900,000 individuals.

Courtesy University of Alabama at Birmingham

Osteoporotic fractures are associated with morbidity and mortality, functional decline, increased nursing home admissions, and a significant economic burden, Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the American College of Rheumatology.

“The number of Americans at risk for fractures on the basis of having osteoporosis is expected to increase by 32% based on the graying of the population,” he said. “Underdiagnosis and undertreatment may be contributing to the increased burden that we are starting to see,” he added.

To assess the impact of osteoporosis management on patients at increased risk for fractures, Dr. Curtis and his colleagues examined temporal trends over 5 years from 885,676 Medicare fee-for-service members with a closed fragility (or osteoporosis-related) fracture between Jan. 1, 2010, and Dec. 31, 2014. The average age of the patients was 81 years; 91% were white, and 94% were women.

The researchers used diagnosis and procedure codes to create an algorithm with a positive predictive value of more than 90%. Individuals with Paget’s disease or a malignancy other than nonmelanoma skin cancer at baseline were excluded.

Overall, use of dual x-ray absorptiometry (DXA) screening in this high-risk population decreased over the study period, with rates during 2010-2014 of 25%, 24%, 23%, 22%, and 16%, respectively. The presence of an osteoporosis diagnosis in the study population decreased over the same period, with rates of 7%, 6%, 6%, 5%, and 4%, respectively. In addition, the percentage of high-risk patients undergoing osteoporosis treatment at the time of fracture during 2010-2014 was 29%, 24%, 20%, 16%, and 11%, respectively.

Despite their history of fracture, more than half of individuals in each year’s database had a comorbidity or were taking a medication that increased fall risk. The most common comorbidity was impaired mobility (about 20% of each yearly cohort), followed by history of falls, history of stroke, impaired vision, muscle atrophy or weakness, and Parkinson’s disease. Approximately half of the patients in each year’s group were taking opioids, and approximately 20% were taking oral corticosteroids.

The findings were limited by several factors, including those common to studies involving administrative claims databases, such as a lack of complete medical and treatment history, lack of diagnostic validation for osteoporosis-related fractures, and lack of information on why use of DXA decreased over time, Dr. Curtis said. However, the results show the need to improve management of individuals at increased risk for falls and fractures to reduce not only the risk of morbidity and mortality, but also the economic impact.

Dr. Curtis disclosed serving as a consultant for Radius Health and Amgen, and the University of Alabama at Birmingham Medical Center received grants from these companies.

SOURCE: Curtis et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1872.

Treatment of osteoporosis in older adults at increased risk for fractures declined from 2010 to 2014, based on a study of nearly 900,000 individuals.

Courtesy University of Alabama at Birmingham

Osteoporotic fractures are associated with morbidity and mortality, functional decline, increased nursing home admissions, and a significant economic burden, Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the American College of Rheumatology.

“The number of Americans at risk for fractures on the basis of having osteoporosis is expected to increase by 32% based on the graying of the population,” he said. “Underdiagnosis and undertreatment may be contributing to the increased burden that we are starting to see,” he added.

To assess the impact of osteoporosis management on patients at increased risk for fractures, Dr. Curtis and his colleagues examined temporal trends over 5 years from 885,676 Medicare fee-for-service members with a closed fragility (or osteoporosis-related) fracture between Jan. 1, 2010, and Dec. 31, 2014. The average age of the patients was 81 years; 91% were white, and 94% were women.

The researchers used diagnosis and procedure codes to create an algorithm with a positive predictive value of more than 90%. Individuals with Paget’s disease or a malignancy other than nonmelanoma skin cancer at baseline were excluded.

Overall, use of dual x-ray absorptiometry (DXA) screening in this high-risk population decreased over the study period, with rates during 2010-2014 of 25%, 24%, 23%, 22%, and 16%, respectively. The presence of an osteoporosis diagnosis in the study population decreased over the same period, with rates of 7%, 6%, 6%, 5%, and 4%, respectively. In addition, the percentage of high-risk patients undergoing osteoporosis treatment at the time of fracture during 2010-2014 was 29%, 24%, 20%, 16%, and 11%, respectively.

Despite their history of fracture, more than half of individuals in each year’s database had a comorbidity or were taking a medication that increased fall risk. The most common comorbidity was impaired mobility (about 20% of each yearly cohort), followed by history of falls, history of stroke, impaired vision, muscle atrophy or weakness, and Parkinson’s disease. Approximately half of the patients in each year’s group were taking opioids, and approximately 20% were taking oral corticosteroids.

The findings were limited by several factors, including those common to studies involving administrative claims databases, such as a lack of complete medical and treatment history, lack of diagnostic validation for osteoporosis-related fractures, and lack of information on why use of DXA decreased over time, Dr. Curtis said. However, the results show the need to improve management of individuals at increased risk for falls and fractures to reduce not only the risk of morbidity and mortality, but also the economic impact.

Dr. Curtis disclosed serving as a consultant for Radius Health and Amgen, and the University of Alabama at Birmingham Medical Center received grants from these companies.

SOURCE: Curtis et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1872.

Treatment of osteoporosis in older adults at increased risk for fractures declined from 2010 to 2014, based on a study of nearly 900,000 individuals.

Courtesy University of Alabama at Birmingham

Osteoporotic fractures are associated with morbidity and mortality, functional decline, increased nursing home admissions, and a significant economic burden, Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, said in a presentation at the annual meeting of the American College of Rheumatology.

“The number of Americans at risk for fractures on the basis of having osteoporosis is expected to increase by 32% based on the graying of the population,” he said. “Underdiagnosis and undertreatment may be contributing to the increased burden that we are starting to see,” he added.

To assess the impact of osteoporosis management on patients at increased risk for fractures, Dr. Curtis and his colleagues examined temporal trends over 5 years from 885,676 Medicare fee-for-service members with a closed fragility (or osteoporosis-related) fracture between Jan. 1, 2010, and Dec. 31, 2014. The average age of the patients was 81 years; 91% were white, and 94% were women.

The researchers used diagnosis and procedure codes to create an algorithm with a positive predictive value of more than 90%. Individuals with Paget’s disease or a malignancy other than nonmelanoma skin cancer at baseline were excluded.

Overall, use of dual x-ray absorptiometry (DXA) screening in this high-risk population decreased over the study period, with rates during 2010-2014 of 25%, 24%, 23%, 22%, and 16%, respectively. The presence of an osteoporosis diagnosis in the study population decreased over the same period, with rates of 7%, 6%, 6%, 5%, and 4%, respectively. In addition, the percentage of high-risk patients undergoing osteoporosis treatment at the time of fracture during 2010-2014 was 29%, 24%, 20%, 16%, and 11%, respectively.

Despite their history of fracture, more than half of individuals in each year’s database had a comorbidity or were taking a medication that increased fall risk. The most common comorbidity was impaired mobility (about 20% of each yearly cohort), followed by history of falls, history of stroke, impaired vision, muscle atrophy or weakness, and Parkinson’s disease. Approximately half of the patients in each year’s group were taking opioids, and approximately 20% were taking oral corticosteroids.

The findings were limited by several factors, including those common to studies involving administrative claims databases, such as a lack of complete medical and treatment history, lack of diagnostic validation for osteoporosis-related fractures, and lack of information on why use of DXA decreased over time, Dr. Curtis said. However, the results show the need to improve management of individuals at increased risk for falls and fractures to reduce not only the risk of morbidity and mortality, but also the economic impact.

Dr. Curtis disclosed serving as a consultant for Radius Health and Amgen, and the University of Alabama at Birmingham Medical Center received grants from these companies.

SOURCE: Curtis et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1872.

Moderate reductions in kidney function in older women are associated with an increased short-term risk of fractures, according to a study published in Osteoporosis International.

However, the longitudinal, population-based cohort study did not find an association with fracture risk either in women older than 80 years or in those with worse kidney function.

“Since the kidneys regulate homeostasis of PTH [parathyroid hormone], phosphate, calcium, and vitamin D, any disruption in function can be expected to disturb bone remodeling and have implications for skeletal health,” wrote Linnea Malmgren, MD, and colleagues from Skåne University Hospital in Malmö, Sweden.

Previous studies have found that a large proportion of older women have reduced kidney function equivalent to a diagnosis of chronic kidney disease and that it is associated with bone loss. However, there have been few studies exploring that association in a population without a diagnosis of chronic kidney disease.

In their study, Dr. Malmgren and colleagues followed 981 women aged 75 years and 685 women aged 80 years, who underwent assessment of kidney function and bone mineral density and were followed up for fracture.

They found that women who experienced an osteoporotic fracture between the ages of 75 and 80 years had significantly lower baseline kidney function, compared with those who did not experience a fracture.

Compared with women with normal kidney function at age 75, women with intermediate kidney function (estimated glomerular filtration rate 45-59 mL/min per 1.73m²⁾ had a significant 2.21-fold higher risk of osteoporotic fracture within 2 years, a 1.51-fold higher risk up to 5 years, and an elevated risk of hip fracture.

A similar trend was seen in women with poor kidney function (eGFR less than 45 mL/min per 1.73m²), but it was not statistically significant.

The analysis also found that kidney function at age 80 years was not significantly associated with long-term fracture risk, nor was there a significant association for 10-year fracture risk in those aged 75 years.

Reduced kidney function was also associated with a higher fracture risk even in women without osteoporosis.

“As expected, fracture risk was high among those with osteoporosis, but risk seemed to further increase in women with both osteoporosis and reduced kidney function, compared with those with osteoporosis and normal function,” the authors reported.

“These findings indicate that implications for bone health and fracture risk might occur in the very common modest reduction of kidney function in the elderly, and also possibly before a diagnosis of CKD-MBD [chronic kidney disease–mineral and bone disorder].”

The study was supported by Lund University; the Swedish Research Council; Forte, Greta and Johan Kock Foundation; A. Påhlsson Foundation; A. Osterlund Foundation; H Järnhardt Foundation; King Gustav V 80-year Fund; Thelma Zoegas Foundation; Swedish Rheumatism Foundation; Skåne University Hospital Research Fund; and the Research and Development Council of Region Skåne, Sweden. No conflicts of interest were declared.

SOURCE: Malmgren L et al. Osteoporos Int. 2019 Nov 21. doi: 10.1007/s00198-019-05152-x.

Moderate reductions in kidney function in older women are associated with an increased short-term risk of fractures, according to a study published in Osteoporosis International.

However, the longitudinal, population-based cohort study did not find an association with fracture risk either in women older than 80 years or in those with worse kidney function.

“Since the kidneys regulate homeostasis of PTH [parathyroid hormone], phosphate, calcium, and vitamin D, any disruption in function can be expected to disturb bone remodeling and have implications for skeletal health,” wrote Linnea Malmgren, MD, and colleagues from Skåne University Hospital in Malmö, Sweden.

Previous studies have found that a large proportion of older women have reduced kidney function equivalent to a diagnosis of chronic kidney disease and that it is associated with bone loss. However, there have been few studies exploring that association in a population without a diagnosis of chronic kidney disease.

In their study, Dr. Malmgren and colleagues followed 981 women aged 75 years and 685 women aged 80 years, who underwent assessment of kidney function and bone mineral density and were followed up for fracture.

They found that women who experienced an osteoporotic fracture between the ages of 75 and 80 years had significantly lower baseline kidney function, compared with those who did not experience a fracture.

Compared with women with normal kidney function at age 75, women with intermediate kidney function (estimated glomerular filtration rate 45-59 mL/min per 1.73m²⁾ had a significant 2.21-fold higher risk of osteoporotic fracture within 2 years, a 1.51-fold higher risk up to 5 years, and an elevated risk of hip fracture.

A similar trend was seen in women with poor kidney function (eGFR less than 45 mL/min per 1.73m²), but it was not statistically significant.

The analysis also found that kidney function at age 80 years was not significantly associated with long-term fracture risk, nor was there a significant association for 10-year fracture risk in those aged 75 years.

Reduced kidney function was also associated with a higher fracture risk even in women without osteoporosis.

“As expected, fracture risk was high among those with osteoporosis, but risk seemed to further increase in women with both osteoporosis and reduced kidney function, compared with those with osteoporosis and normal function,” the authors reported.

“These findings indicate that implications for bone health and fracture risk might occur in the very common modest reduction of kidney function in the elderly, and also possibly before a diagnosis of CKD-MBD [chronic kidney disease–mineral and bone disorder].”

The study was supported by Lund University; the Swedish Research Council; Forte, Greta and Johan Kock Foundation; A. Påhlsson Foundation; A. Osterlund Foundation; H Järnhardt Foundation; King Gustav V 80-year Fund; Thelma Zoegas Foundation; Swedish Rheumatism Foundation; Skåne University Hospital Research Fund; and the Research and Development Council of Region Skåne, Sweden. No conflicts of interest were declared.

SOURCE: Malmgren L et al. Osteoporos Int. 2019 Nov 21. doi: 10.1007/s00198-019-05152-x.

Moderate reductions in kidney function in older women are associated with an increased short-term risk of fractures, according to a study published in Osteoporosis International.

However, the longitudinal, population-based cohort study did not find an association with fracture risk either in women older than 80 years or in those with worse kidney function.

“Since the kidneys regulate homeostasis of PTH [parathyroid hormone], phosphate, calcium, and vitamin D, any disruption in function can be expected to disturb bone remodeling and have implications for skeletal health,” wrote Linnea Malmgren, MD, and colleagues from Skåne University Hospital in Malmö, Sweden.

Previous studies have found that a large proportion of older women have reduced kidney function equivalent to a diagnosis of chronic kidney disease and that it is associated with bone loss. However, there have been few studies exploring that association in a population without a diagnosis of chronic kidney disease.

In their study, Dr. Malmgren and colleagues followed 981 women aged 75 years and 685 women aged 80 years, who underwent assessment of kidney function and bone mineral density and were followed up for fracture.

They found that women who experienced an osteoporotic fracture between the ages of 75 and 80 years had significantly lower baseline kidney function, compared with those who did not experience a fracture.

Compared with women with normal kidney function at age 75, women with intermediate kidney function (estimated glomerular filtration rate 45-59 mL/min per 1.73m²⁾ had a significant 2.21-fold higher risk of osteoporotic fracture within 2 years, a 1.51-fold higher risk up to 5 years, and an elevated risk of hip fracture.

A similar trend was seen in women with poor kidney function (eGFR less than 45 mL/min per 1.73m²), but it was not statistically significant.

The analysis also found that kidney function at age 80 years was not significantly associated with long-term fracture risk, nor was there a significant association for 10-year fracture risk in those aged 75 years.

Reduced kidney function was also associated with a higher fracture risk even in women without osteoporosis.

“As expected, fracture risk was high among those with osteoporosis, but risk seemed to further increase in women with both osteoporosis and reduced kidney function, compared with those with osteoporosis and normal function,” the authors reported.

“These findings indicate that implications for bone health and fracture risk might occur in the very common modest reduction of kidney function in the elderly, and also possibly before a diagnosis of CKD-MBD [chronic kidney disease–mineral and bone disorder].”

The study was supported by Lund University; the Swedish Research Council; Forte, Greta and Johan Kock Foundation; A. Påhlsson Foundation; A. Osterlund Foundation; H Järnhardt Foundation; King Gustav V 80-year Fund; Thelma Zoegas Foundation; Swedish Rheumatism Foundation; Skåne University Hospital Research Fund; and the Research and Development Council of Region Skåne, Sweden. No conflicts of interest were declared.

SOURCE: Malmgren L et al. Osteoporos Int. 2019 Nov 21. doi: 10.1007/s00198-019-05152-x.

Prior to last year, this column was titled “Update on osteoporosis.” My observation, however, is that too many ObGyn providers simply measure bone mass (known as bone mineral density, or BMD), label a patient as normal, osteopenic, or osteoporotic, and then consider pharmacotherapy. The FRAX fracture prediction algorithm, which incorporates age, weight, height, history of any previous fracture, family history of hip fracture, current smoking, use of glucocorticoid medications, and any history of rheumatoid arthritis, has refined the screening process somewhat, if and when it is utilized. As clinicians, we should never lose sight of our goal: to prevent fragility fractures. Having osteoporosis increases that risk, but not having osteoporosis does not eliminate it.

In this Update, I highlight various ways in which work published this past year may help us to improve our patients’ bone health and reduce fragility fractures.

Updated ISCD guidance emphasizes appropriate BMD testing, use of the
Z-score, and terminology 

International Society for Clinical Densitometry. 2019 ISCD Official Positions-Adult. June 2019.  https://www.iscd.org/official-positions/2019-ISCD-official-positions-adult. 

Continue to: Indications for BMD testing...

Indications for BMD testing 

The ISCD's indications for BMD testing remain for women age 65 and older. For postmenopausal women younger than age 65, a BMD test is indicated if they have a risk factor for low bone mass, such as 1) low body weight, 2) prior fracture, 3) high-risk medication use, or 4) a disease or condition associated with bone loss. A BMD test also is indicated for women during the menopausal transition with clinical risk factors for fracture, such as low body weight, prior fracture, or high-risk medication use. Interestingly, the ISCD recommendation for men is similar but uses age 70 for this group. 

In addition, the ISCD recommends BMD testing in adults with a fragility fracture, with a disease or condition associated with low bone mass, or taking medications associated with low bone mass, as well as for anyone being considered for pharmacologic therapy, being treated (to monitor treatment effect), not receiving therapy in whom evidence of bone loss would lead to treatment, and in women discontinuing estrogen who should be considered for BMD testing according to the indications already mentioned. 

Sites to assess for osteoporosis. The World Health Organization international reference standard for osteoporosis diagnosis is a T-score of -2.5 or less at the femoral neck. The reference standard, from which the T-score is calculated, is for white women aged 20 to 29 years of age from the database of the Third National Health and Nutrition Examination Survey. Osteoporosis also may be diagnosed in postmenopausal women if the T-score of the lumbar spine, total hip, or femoral neck is -2.5 or less. In certain circumstances, the 33% radius (also called the one-third radius) may be utilized. Other hip regions of interest, including Ward's area and the greater trochanter, should not be used for diagnosis. 

The skeletal sites at which to measure BMD include the anteroposterior of the spine and hip in all patients. In terms of the spine, use L1-L4 for spine BMD measurement. However, exclude vertebrae that are affected by local structural changes or artifact. Use 3 vertebrae if 4 cannot be used, and 2 if 3 cannot be used. BMD-based diagnostic classification should not be made using a single vertebra. Anatomically abnormal vertebrae may be excluded from analysis if they are clearly abnormal and nonassessable within the resolution of the system, or if there is more than a 1.0 T-score difference between the vertebra in question and adjacent vertebrae. When vertebrae are excluded, the BMD of the remaining vertebrae are used to derive the T-score. 

For BMD measurement at the hip, the femoral neck or total proximal femur—whichever is lowest—should be used. Either hip may be measured. Data are insufficient on whether mean T-scores for bilateral hip BMD should be used for diagnosis. 

Terminology. While the ISCD retains the term osteopenia, the term low bone mass or low bone density is preferred. People with low bone mass or density are not necessarily at high fracture risk. 

Concerning BMD reporting in women prior to menopause, Z-scores, not T-scores, are preferred. A Z-score of -2.0 or lower is defined as "below the expected range for age"; a Z-score above -2.0 is "within the expected range for age." 

Use of serial BMD testing 

Finally, regarding serial BMD measurements, such testing in combination with clinical assessment of fracture risk can be used to determine whether treatment should be initiated in untreated patients. Furthermore, serial BMD testing can monitor a patient's response to therapy by finding an increase or stability of bone density. It should be used to monitor individuals following cessation of osteoporosis drug therapy. Serial BMD testing can detect loss of bone density, indicating the need to assess treatment adherence, evaluate possible secondary causes of osteoporosis, and possibly re-evaluate therapeutic options. 

Intervals between BMD testing should be determined according to each patient's clinical status. Typically, 1 year after initiating or changing therapy is appropriate, with longer intervals once therapeutic effect is established.

Continue to: Dyspareunia drug has positive effects on bone...

Dyspareunia drug has positive effects on bone 

de Villiers TJ, Altomare C, Particco M, et al. Effects of ospemifene on bone in postmenopausal women. Climacteric. 2019;22:442-447. 

Previously, ospemifene effectively reduced bone loss in ovariectomized rats, with activity comparable to that of estradiol and raloxifene.³ Clinical data from 3 phase 1 or 2 clinical trials found that ospemifene 60 mg/day had a positive effect on biochemical markers for bone turnover in healthy postmenopausal women, with significant improvements relative to placebo and effects comparable to those of raloxifene.⁴ 

Effects on bone formation/resorption biomarkers 

In a recent study, de Villiers and colleagues reported the first phase 3 trial that looked at markers of bone formation and bone resorption.⁵ A total of 316 women were randomly assigned to receive ospemifene, and 315 received placebo.

Demographic and baseline characteristics were similar between treatment groups. Participants' mean age was approximately 60 years, mean body mass index (BMI) was 27.2 kg/m2, and mean duration of VVA was 8 to 9 years. Serum levels of 9 bone biomarkers were similar between groups at baseline. 

At week 12, all 5 markers of bone resorption improved with ospemifene treatment, and 3 of the 5 (NTX, CTX, and TRACP-5b) did so in a statistically significant fashion compared with placebo (P≤.02). In addition, at week 12, all 4 markers of bone formation improved with ospemifene treatment compared with placebo (P≤.008). Furthermore, lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤ 5 years or
> 5 years) or baseline BMD, whether normal, osteopenic, or osteoporotic. 

Interpret results cautiously 

The authors caution that the data are limited to biochemical markers rather than fracture or BMD. It is known that there is good correlation between biochemical markers for bone turnover and the occurrence of fracture.⁶ 

Continue to: Sarcopenia adds to osteoporotic risk for fractures...

Sarcopenia adds to osteoporotic risk for fractures 

Lima RM, de Oliveira RJ, Raposo R, et al. Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women. Arch Osteoporos. 2019;14:38. 

In 1989, the term sarcopenia was introduced to refer to the age-related decline in skeletal muscle mass.⁸ Currently, sarcopenia is defined as a progressive decline in muscle mass, strength, and physical function, thus increasing the risk for various adverse outcomes, including osteoporosis.⁹ Although muscle and bone tissues differ morphologically, their functioning is closely interconnected. 

The sarcopenia-osteoporosis connection 

Lima and colleagues sought to investigate the relationship between sarcopenia and osteoporosis.¹⁰ They measured women's fat free mass with dual-energy x-ray absorptiometry (DXA) scanning, muscle strength using a dynamometer to measure knee extension torque while participants were seated, and functional performance using the timed "up and go test" in which participants were timed as they got up from a chair, walked 3 meters around a cone, and returned to sit in the chair.^10,11 

The authors used definitions from the European Working Group on Sarcopenia in Older People (EWGSOP). Participants who had normal results in all 3 domains were considered nonsarcopenic. Presarcopenia was defined as having low fat free mass on DXA scanning but normal strength and function. Participants who had low fat free mass and either low strength or low function were labeled as having sarcopenia. Severe sarcopenia was defined as abnormal results in all 3 domains. 

Two hundred thirty-four women (mean age, 68.3 years; range, 60-80) underwent BMD testing and were evaluated according to the 3 domains of possible sarcopenia. All were community dwelling and did not have cognitive impairment or functional dependency. 

The rates of osteoporosis were 15.8%, 19.2%, 35.3%, and 46.2% for nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia, respectively (P=.002). Whole-body and femoral neck BMD values were significantly lower among all sarcopenia stages when compared with nonsarcopenia (P<.05). The severe sarcopenia group showed the lowest lumbar spine T-scores (P<.05). When clustered, sarcopenia and severe sarcopenia presented a significantly higher risk for osteoporosis (odds ratio, 3.4; 95% confidence interval [CI], 1.5-7.8). 

Consider sarcopenia a risk factor 

The authors concluded that these "results provide support for the concept that a dose-response relationship exists between sarcopenia stages, BMD, and the presence of osteoporosis. These findings strengthen the clinical significance of the EWGSOP sarcopenia definitions and indicate that severe sarcopenia should be viewed with attention by healthcare professionals." 

Continue to: Certain characteristics may offset fracture risk in aromatase inhibitor users...

Certain characteristics may offset fracture risk in aromatase inhibitor users 

Leslie WD, Morin SN, Lix LM, et al. Fracture risk in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. Oncologist. 2019;24:1432-1438. 

The use of AIs increases bone turnover and induces bone loss at trabecular-rich bone sites at an average rate of 1% to 3% per year, with reports of up to a threefold increased fracture incidence.¹³ By contrast, a large nationwide population-based cohort study using US Medicare data identified minimal fracture risk from AI use compared with tamoxifen use (11% higher for nonvertebral fractures, not significantly increased for hip fractures).¹⁴ 

An article published previously in this column reported that women on AIs treated with intravenous zoledronic acid had improvements in BMD, while women treated with denosumab had statistically significant fewer fractures compared with those receiving placebo, whether they had normal bone mass, osteopenia, or osteoporosis at
baseline.^15-17
 

Data derived from a population-based BMD registry 

In a recent cohort study, Leslie and colleagues offer the opinion that "observations in the clinical trial setting may differ from routine clinical practice."¹⁸ The authors examined fracture outcomes using a large clinical registry of BMD results from women in Manitoba, Canada. They identified women at least 40 years of age initiating AI therapy for breast cancer (n = 1,775), women with breast cancer not receiving AI therapy (n = 1,016), and women from the general population without breast cancer (n = 34,205). 

Fracture outcomes were assessed after a mean of 6.2 years for the AI users, all of whom had at least 12 months of AI exposure. At baseline, AI users had higher BMI, higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all P<.001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% CI, 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. 

Results challenge prevailing view 

Thus, the authors concluded that higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, the authors stated that their findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fracture.  

Prior to last year, this column was titled “Update on osteoporosis.” My observation, however, is that too many ObGyn providers simply measure bone mass (known as bone mineral density, or BMD), label a patient as normal, osteopenic, or osteoporotic, and then consider pharmacotherapy. The FRAX fracture prediction algorithm, which incorporates age, weight, height, history of any previous fracture, family history of hip fracture, current smoking, use of glucocorticoid medications, and any history of rheumatoid arthritis, has refined the screening process somewhat, if and when it is utilized. As clinicians, we should never lose sight of our goal: to prevent fragility fractures. Having osteoporosis increases that risk, but not having osteoporosis does not eliminate it.

In this Update, I highlight various ways in which work published this past year may help us to improve our patients’ bone health and reduce fragility fractures.

Updated ISCD guidance emphasizes appropriate BMD testing, use of the
Z-score, and terminology 

International Society for Clinical Densitometry. 2019 ISCD Official Positions-Adult. June 2019.  https://www.iscd.org/official-positions/2019-ISCD-official-positions-adult. 

Continue to: Indications for BMD testing...

Indications for BMD testing 

The ISCD's indications for BMD testing remain for women age 65 and older. For postmenopausal women younger than age 65, a BMD test is indicated if they have a risk factor for low bone mass, such as 1) low body weight, 2) prior fracture, 3) high-risk medication use, or 4) a disease or condition associated with bone loss. A BMD test also is indicated for women during the menopausal transition with clinical risk factors for fracture, such as low body weight, prior fracture, or high-risk medication use. Interestingly, the ISCD recommendation for men is similar but uses age 70 for this group. 

In addition, the ISCD recommends BMD testing in adults with a fragility fracture, with a disease or condition associated with low bone mass, or taking medications associated with low bone mass, as well as for anyone being considered for pharmacologic therapy, being treated (to monitor treatment effect), not receiving therapy in whom evidence of bone loss would lead to treatment, and in women discontinuing estrogen who should be considered for BMD testing according to the indications already mentioned. 

Sites to assess for osteoporosis. The World Health Organization international reference standard for osteoporosis diagnosis is a T-score of -2.5 or less at the femoral neck. The reference standard, from which the T-score is calculated, is for white women aged 20 to 29 years of age from the database of the Third National Health and Nutrition Examination Survey. Osteoporosis also may be diagnosed in postmenopausal women if the T-score of the lumbar spine, total hip, or femoral neck is -2.5 or less. In certain circumstances, the 33% radius (also called the one-third radius) may be utilized. Other hip regions of interest, including Ward's area and the greater trochanter, should not be used for diagnosis. 

The skeletal sites at which to measure BMD include the anteroposterior of the spine and hip in all patients. In terms of the spine, use L1-L4 for spine BMD measurement. However, exclude vertebrae that are affected by local structural changes or artifact. Use 3 vertebrae if 4 cannot be used, and 2 if 3 cannot be used. BMD-based diagnostic classification should not be made using a single vertebra. Anatomically abnormal vertebrae may be excluded from analysis if they are clearly abnormal and nonassessable within the resolution of the system, or if there is more than a 1.0 T-score difference between the vertebra in question and adjacent vertebrae. When vertebrae are excluded, the BMD of the remaining vertebrae are used to derive the T-score. 

For BMD measurement at the hip, the femoral neck or total proximal femur—whichever is lowest—should be used. Either hip may be measured. Data are insufficient on whether mean T-scores for bilateral hip BMD should be used for diagnosis. 

Terminology. While the ISCD retains the term osteopenia, the term low bone mass or low bone density is preferred. People with low bone mass or density are not necessarily at high fracture risk. 

Concerning BMD reporting in women prior to menopause, Z-scores, not T-scores, are preferred. A Z-score of -2.0 or lower is defined as "below the expected range for age"; a Z-score above -2.0 is "within the expected range for age." 

Use of serial BMD testing 

Finally, regarding serial BMD measurements, such testing in combination with clinical assessment of fracture risk can be used to determine whether treatment should be initiated in untreated patients. Furthermore, serial BMD testing can monitor a patient's response to therapy by finding an increase or stability of bone density. It should be used to monitor individuals following cessation of osteoporosis drug therapy. Serial BMD testing can detect loss of bone density, indicating the need to assess treatment adherence, evaluate possible secondary causes of osteoporosis, and possibly re-evaluate therapeutic options. 

Intervals between BMD testing should be determined according to each patient's clinical status. Typically, 1 year after initiating or changing therapy is appropriate, with longer intervals once therapeutic effect is established.

Continue to: Dyspareunia drug has positive effects on bone...

Dyspareunia drug has positive effects on bone 

de Villiers TJ, Altomare C, Particco M, et al. Effects of ospemifene on bone in postmenopausal women. Climacteric. 2019;22:442-447. 

Previously, ospemifene effectively reduced bone loss in ovariectomized rats, with activity comparable to that of estradiol and raloxifene.³ Clinical data from 3 phase 1 or 2 clinical trials found that ospemifene 60 mg/day had a positive effect on biochemical markers for bone turnover in healthy postmenopausal women, with significant improvements relative to placebo and effects comparable to those of raloxifene.⁴ 

Effects on bone formation/resorption biomarkers 

In a recent study, de Villiers and colleagues reported the first phase 3 trial that looked at markers of bone formation and bone resorption.⁵ A total of 316 women were randomly assigned to receive ospemifene, and 315 received placebo.

Demographic and baseline characteristics were similar between treatment groups. Participants' mean age was approximately 60 years, mean body mass index (BMI) was 27.2 kg/m2, and mean duration of VVA was 8 to 9 years. Serum levels of 9 bone biomarkers were similar between groups at baseline. 

At week 12, all 5 markers of bone resorption improved with ospemifene treatment, and 3 of the 5 (NTX, CTX, and TRACP-5b) did so in a statistically significant fashion compared with placebo (P≤.02). In addition, at week 12, all 4 markers of bone formation improved with ospemifene treatment compared with placebo (P≤.008). Furthermore, lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤ 5 years or
> 5 years) or baseline BMD, whether normal, osteopenic, or osteoporotic. 

Interpret results cautiously 

The authors caution that the data are limited to biochemical markers rather than fracture or BMD. It is known that there is good correlation between biochemical markers for bone turnover and the occurrence of fracture.⁶ 

Continue to: Sarcopenia adds to osteoporotic risk for fractures...

Sarcopenia adds to osteoporotic risk for fractures 

Lima RM, de Oliveira RJ, Raposo R, et al. Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women. Arch Osteoporos. 2019;14:38. 

In 1989, the term sarcopenia was introduced to refer to the age-related decline in skeletal muscle mass.⁸ Currently, sarcopenia is defined as a progressive decline in muscle mass, strength, and physical function, thus increasing the risk for various adverse outcomes, including osteoporosis.⁹ Although muscle and bone tissues differ morphologically, their functioning is closely interconnected. 

The sarcopenia-osteoporosis connection 

Lima and colleagues sought to investigate the relationship between sarcopenia and osteoporosis.¹⁰ They measured women's fat free mass with dual-energy x-ray absorptiometry (DXA) scanning, muscle strength using a dynamometer to measure knee extension torque while participants were seated, and functional performance using the timed "up and go test" in which participants were timed as they got up from a chair, walked 3 meters around a cone, and returned to sit in the chair.^10,11 

The authors used definitions from the European Working Group on Sarcopenia in Older People (EWGSOP). Participants who had normal results in all 3 domains were considered nonsarcopenic. Presarcopenia was defined as having low fat free mass on DXA scanning but normal strength and function. Participants who had low fat free mass and either low strength or low function were labeled as having sarcopenia. Severe sarcopenia was defined as abnormal results in all 3 domains. 

Two hundred thirty-four women (mean age, 68.3 years; range, 60-80) underwent BMD testing and were evaluated according to the 3 domains of possible sarcopenia. All were community dwelling and did not have cognitive impairment or functional dependency. 

The rates of osteoporosis were 15.8%, 19.2%, 35.3%, and 46.2% for nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia, respectively (P=.002). Whole-body and femoral neck BMD values were significantly lower among all sarcopenia stages when compared with nonsarcopenia (P<.05). The severe sarcopenia group showed the lowest lumbar spine T-scores (P<.05). When clustered, sarcopenia and severe sarcopenia presented a significantly higher risk for osteoporosis (odds ratio, 3.4; 95% confidence interval [CI], 1.5-7.8). 

Consider sarcopenia a risk factor 

The authors concluded that these "results provide support for the concept that a dose-response relationship exists between sarcopenia stages, BMD, and the presence of osteoporosis. These findings strengthen the clinical significance of the EWGSOP sarcopenia definitions and indicate that severe sarcopenia should be viewed with attention by healthcare professionals." 

Continue to: Certain characteristics may offset fracture risk in aromatase inhibitor users...

Certain characteristics may offset fracture risk in aromatase inhibitor users 

Leslie WD, Morin SN, Lix LM, et al. Fracture risk in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. Oncologist. 2019;24:1432-1438. 

The use of AIs increases bone turnover and induces bone loss at trabecular-rich bone sites at an average rate of 1% to 3% per year, with reports of up to a threefold increased fracture incidence.¹³ By contrast, a large nationwide population-based cohort study using US Medicare data identified minimal fracture risk from AI use compared with tamoxifen use (11% higher for nonvertebral fractures, not significantly increased for hip fractures).¹⁴ 

An article published previously in this column reported that women on AIs treated with intravenous zoledronic acid had improvements in BMD, while women treated with denosumab had statistically significant fewer fractures compared with those receiving placebo, whether they had normal bone mass, osteopenia, or osteoporosis at
baseline.^15-17
 

Data derived from a population-based BMD registry 

In a recent cohort study, Leslie and colleagues offer the opinion that "observations in the clinical trial setting may differ from routine clinical practice."¹⁸ The authors examined fracture outcomes using a large clinical registry of BMD results from women in Manitoba, Canada. They identified women at least 40 years of age initiating AI therapy for breast cancer (n = 1,775), women with breast cancer not receiving AI therapy (n = 1,016), and women from the general population without breast cancer (n = 34,205). 

Fracture outcomes were assessed after a mean of 6.2 years for the AI users, all of whom had at least 12 months of AI exposure. At baseline, AI users had higher BMI, higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all P<.001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% CI, 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. 

Results challenge prevailing view 

Thus, the authors concluded that higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, the authors stated that their findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fracture.  

Prior to last year, this column was titled “Update on osteoporosis.” My observation, however, is that too many ObGyn providers simply measure bone mass (known as bone mineral density, or BMD), label a patient as normal, osteopenic, or osteoporotic, and then consider pharmacotherapy. The FRAX fracture prediction algorithm, which incorporates age, weight, height, history of any previous fracture, family history of hip fracture, current smoking, use of glucocorticoid medications, and any history of rheumatoid arthritis, has refined the screening process somewhat, if and when it is utilized. As clinicians, we should never lose sight of our goal: to prevent fragility fractures. Having osteoporosis increases that risk, but not having osteoporosis does not eliminate it.

In this Update, I highlight various ways in which work published this past year may help us to improve our patients’ bone health and reduce fragility fractures.

Updated ISCD guidance emphasizes appropriate BMD testing, use of the
Z-score, and terminology 

International Society for Clinical Densitometry. 2019 ISCD Official Positions-Adult. June 2019.  https://www.iscd.org/official-positions/2019-ISCD-official-positions-adult. 

Continue to: Indications for BMD testing...

Indications for BMD testing 

The ISCD's indications for BMD testing remain for women age 65 and older. For postmenopausal women younger than age 65, a BMD test is indicated if they have a risk factor for low bone mass, such as 1) low body weight, 2) prior fracture, 3) high-risk medication use, or 4) a disease or condition associated with bone loss. A BMD test also is indicated for women during the menopausal transition with clinical risk factors for fracture, such as low body weight, prior fracture, or high-risk medication use. Interestingly, the ISCD recommendation for men is similar but uses age 70 for this group. 

In addition, the ISCD recommends BMD testing in adults with a fragility fracture, with a disease or condition associated with low bone mass, or taking medications associated with low bone mass, as well as for anyone being considered for pharmacologic therapy, being treated (to monitor treatment effect), not receiving therapy in whom evidence of bone loss would lead to treatment, and in women discontinuing estrogen who should be considered for BMD testing according to the indications already mentioned. 

Sites to assess for osteoporosis. The World Health Organization international reference standard for osteoporosis diagnosis is a T-score of -2.5 or less at the femoral neck. The reference standard, from which the T-score is calculated, is for white women aged 20 to 29 years of age from the database of the Third National Health and Nutrition Examination Survey. Osteoporosis also may be diagnosed in postmenopausal women if the T-score of the lumbar spine, total hip, or femoral neck is -2.5 or less. In certain circumstances, the 33% radius (also called the one-third radius) may be utilized. Other hip regions of interest, including Ward's area and the greater trochanter, should not be used for diagnosis. 

The skeletal sites at which to measure BMD include the anteroposterior of the spine and hip in all patients. In terms of the spine, use L1-L4 for spine BMD measurement. However, exclude vertebrae that are affected by local structural changes or artifact. Use 3 vertebrae if 4 cannot be used, and 2 if 3 cannot be used. BMD-based diagnostic classification should not be made using a single vertebra. Anatomically abnormal vertebrae may be excluded from analysis if they are clearly abnormal and nonassessable within the resolution of the system, or if there is more than a 1.0 T-score difference between the vertebra in question and adjacent vertebrae. When vertebrae are excluded, the BMD of the remaining vertebrae are used to derive the T-score. 

For BMD measurement at the hip, the femoral neck or total proximal femur—whichever is lowest—should be used. Either hip may be measured. Data are insufficient on whether mean T-scores for bilateral hip BMD should be used for diagnosis. 

Terminology. While the ISCD retains the term osteopenia, the term low bone mass or low bone density is preferred. People with low bone mass or density are not necessarily at high fracture risk. 

Concerning BMD reporting in women prior to menopause, Z-scores, not T-scores, are preferred. A Z-score of -2.0 or lower is defined as "below the expected range for age"; a Z-score above -2.0 is "within the expected range for age." 

Use of serial BMD testing 

Finally, regarding serial BMD measurements, such testing in combination with clinical assessment of fracture risk can be used to determine whether treatment should be initiated in untreated patients. Furthermore, serial BMD testing can monitor a patient's response to therapy by finding an increase or stability of bone density. It should be used to monitor individuals following cessation of osteoporosis drug therapy. Serial BMD testing can detect loss of bone density, indicating the need to assess treatment adherence, evaluate possible secondary causes of osteoporosis, and possibly re-evaluate therapeutic options. 

Intervals between BMD testing should be determined according to each patient's clinical status. Typically, 1 year after initiating or changing therapy is appropriate, with longer intervals once therapeutic effect is established.

Continue to: Dyspareunia drug has positive effects on bone...

Dyspareunia drug has positive effects on bone 

de Villiers TJ, Altomare C, Particco M, et al. Effects of ospemifene on bone in postmenopausal women. Climacteric. 2019;22:442-447. 

Previously, ospemifene effectively reduced bone loss in ovariectomized rats, with activity comparable to that of estradiol and raloxifene.³ Clinical data from 3 phase 1 or 2 clinical trials found that ospemifene 60 mg/day had a positive effect on biochemical markers for bone turnover in healthy postmenopausal women, with significant improvements relative to placebo and effects comparable to those of raloxifene.⁴ 

Effects on bone formation/resorption biomarkers 

In a recent study, de Villiers and colleagues reported the first phase 3 trial that looked at markers of bone formation and bone resorption.⁵ A total of 316 women were randomly assigned to receive ospemifene, and 315 received placebo.

Demographic and baseline characteristics were similar between treatment groups. Participants' mean age was approximately 60 years, mean body mass index (BMI) was 27.2 kg/m2, and mean duration of VVA was 8 to 9 years. Serum levels of 9 bone biomarkers were similar between groups at baseline. 

At week 12, all 5 markers of bone resorption improved with ospemifene treatment, and 3 of the 5 (NTX, CTX, and TRACP-5b) did so in a statistically significant fashion compared with placebo (P≤.02). In addition, at week 12, all 4 markers of bone formation improved with ospemifene treatment compared with placebo (P≤.008). Furthermore, lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤ 5 years or
> 5 years) or baseline BMD, whether normal, osteopenic, or osteoporotic. 

Interpret results cautiously 

The authors caution that the data are limited to biochemical markers rather than fracture or BMD. It is known that there is good correlation between biochemical markers for bone turnover and the occurrence of fracture.⁶ 

Continue to: Sarcopenia adds to osteoporotic risk for fractures...

Sarcopenia adds to osteoporotic risk for fractures 

Lima RM, de Oliveira RJ, Raposo R, et al. Stages of sarcopenia, bone mineral density, and the prevalence of osteoporosis in older women. Arch Osteoporos. 2019;14:38. 

In 1989, the term sarcopenia was introduced to refer to the age-related decline in skeletal muscle mass.⁸ Currently, sarcopenia is defined as a progressive decline in muscle mass, strength, and physical function, thus increasing the risk for various adverse outcomes, including osteoporosis.⁹ Although muscle and bone tissues differ morphologically, their functioning is closely interconnected. 

The sarcopenia-osteoporosis connection 

Lima and colleagues sought to investigate the relationship between sarcopenia and osteoporosis.¹⁰ They measured women's fat free mass with dual-energy x-ray absorptiometry (DXA) scanning, muscle strength using a dynamometer to measure knee extension torque while participants were seated, and functional performance using the timed "up and go test" in which participants were timed as they got up from a chair, walked 3 meters around a cone, and returned to sit in the chair.^10,11 

The authors used definitions from the European Working Group on Sarcopenia in Older People (EWGSOP). Participants who had normal results in all 3 domains were considered nonsarcopenic. Presarcopenia was defined as having low fat free mass on DXA scanning but normal strength and function. Participants who had low fat free mass and either low strength or low function were labeled as having sarcopenia. Severe sarcopenia was defined as abnormal results in all 3 domains. 

Two hundred thirty-four women (mean age, 68.3 years; range, 60-80) underwent BMD testing and were evaluated according to the 3 domains of possible sarcopenia. All were community dwelling and did not have cognitive impairment or functional dependency. 

The rates of osteoporosis were 15.8%, 19.2%, 35.3%, and 46.2% for nonsarcopenia, presarcopenia, sarcopenia, and severe sarcopenia, respectively (P=.002). Whole-body and femoral neck BMD values were significantly lower among all sarcopenia stages when compared with nonsarcopenia (P<.05). The severe sarcopenia group showed the lowest lumbar spine T-scores (P<.05). When clustered, sarcopenia and severe sarcopenia presented a significantly higher risk for osteoporosis (odds ratio, 3.4; 95% confidence interval [CI], 1.5-7.8). 

Consider sarcopenia a risk factor 

The authors concluded that these "results provide support for the concept that a dose-response relationship exists between sarcopenia stages, BMD, and the presence of osteoporosis. These findings strengthen the clinical significance of the EWGSOP sarcopenia definitions and indicate that severe sarcopenia should be viewed with attention by healthcare professionals." 

Continue to: Certain characteristics may offset fracture risk in aromatase inhibitor users...

Certain characteristics may offset fracture risk in aromatase inhibitor users 

Leslie WD, Morin SN, Lix LM, et al. Fracture risk in women with breast cancer initiating aromatase inhibitor therapy: a registry-based cohort study. Oncologist. 2019;24:1432-1438. 

The use of AIs increases bone turnover and induces bone loss at trabecular-rich bone sites at an average rate of 1% to 3% per year, with reports of up to a threefold increased fracture incidence.¹³ By contrast, a large nationwide population-based cohort study using US Medicare data identified minimal fracture risk from AI use compared with tamoxifen use (11% higher for nonvertebral fractures, not significantly increased for hip fractures).¹⁴ 

An article published previously in this column reported that women on AIs treated with intravenous zoledronic acid had improvements in BMD, while women treated with denosumab had statistically significant fewer fractures compared with those receiving placebo, whether they had normal bone mass, osteopenia, or osteoporosis at
baseline.^15-17
 

Data derived from a population-based BMD registry 

In a recent cohort study, Leslie and colleagues offer the opinion that "observations in the clinical trial setting may differ from routine clinical practice."¹⁸ The authors examined fracture outcomes using a large clinical registry of BMD results from women in Manitoba, Canada. They identified women at least 40 years of age initiating AI therapy for breast cancer (n = 1,775), women with breast cancer not receiving AI therapy (n = 1,016), and women from the general population without breast cancer (n = 34,205). 

Fracture outcomes were assessed after a mean of 6.2 years for the AI users, all of whom had at least 12 months of AI exposure. At baseline, AI users had higher BMI, higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all P<.001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% CI, 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population. 

Results challenge prevailing view 

Thus, the authors concluded that higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, the authors stated that their findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fracture.