Osteoporosis

MADRID – The risk of osteoporotic fracture associated with hematopoietic stem cell transplantation (HSCT) could be assessed using the Fracture Risk Assessment Tool (FRAX), researchers from the University of Texas MD Anderson Cancer Center have found.

In a retrospective cohort study, Huifang Lu, MD, and her collaborators found that FRAX could predict the risk of fracture with reasonable accuracy. The area under the receiver operating characteristic curve was 0.66 for predicting a fracture 10 years after HSCT.

“Current guidelines recommend the evaluation of bone health at 1 year following the transplant, but we recommend that this needs to happen at a much earlier time,” Dr. Lu said at the European Congress of Rheumatology.

Determining how to assess risk earlier and prevent bone loss remains a challenge, however. FRAX is an easy and quick tool to use, but its predictive ability is modest, she said.

As the finding comes from a retrospective study, prospective evaluation of FRAX is needed in HSCT patients. If shown predictive in this setting, bone health could be assessed earlier using FRAX, ideally at or before the time of the transplant, to allow appropriate action to be taken, such as prescribing bisphosphonates to those identified to be at high risk.

There is no consensus on preventing and treating bone loss following HSCT, said Dr. Lu. In a meta-analysis performed by Dr. Lu and her associates (Bone Marrow Transplant. 2017;52[5]:663-70), less bone loss was seen in patients who received a bisphosphonate.

As the use of HSCT has expanded over the past two decades, there is an expanding population of survivors with potential long-term effects such as bone loss and a higher risk of fractures, compared with the general population, Dr. Lu explained.

The FRAX tool takes into account pre-HSCT factors such as age, smoking status, alcohol use, prior fracture, body mass index, and corticosteroid use. This can be considered in association with the fracture risk related to the various conditioning and supporting regimens that patients receive around the time of their transplants.

The study included 5,170 adult patients who had undergone HSCT at the University of Texas MD Anderson Cancer Center over a 10-year period. Patients were considered to have entered the cohort at the time of their transplants, Dr. Lu said. Their history of osteoporotic fractures up to 3.3 years later was obtained and verified by radiology and physician assessment. FRAX probabilities were then derived from baseline information.

The mean age of patients included was 52 years, 57% were male and 75% were white. One-quarter had experienced a prior fracture. Of note, 26% of the cohort underwent HSCT for multiple myeloma, 70% of whom had already had a fracture, compared with 9% of those who underwent HSCT for another reason such as leukemia or lymphoma.

Multivariate analyses were performed with and without considering death as a competing risk, and similar results were obtained. Higher FRAX scores (20 or greater) were more likely to be recorded in individuals who sustained a fracture than in those who did not. Patients who had an allogeneic HSCT were 15% more likely to have a fracture as those who received an autologous transplant. Perhaps not surprisingly, patients with multiple myeloma were more likely than those who had HSCT for other reasons to sustain a fracture by 10 years based on FRAX results (hazard ratio, 3.16).

Future research needs to look at the optimal cut offs for FRAX scores predictive of events and see if there is any association between the loss of bone and fracture risk. There also needs to be an evaluation of the use of concomitant medications and health economic analyses performed.

Dr. Lu had no conflicts of interest. The study was funded by the Rolanette and Berdon Lawrence Bone Disease Program of Texas and via Cancer Survivorship Research Seed Monday Grants from the University Cancer Foundation and Duncan Family Institute for Cancer Prevention and Risk Assessment to the University of Texas MD Anderson Cancer Center.

MADRID – The risk of osteoporotic fracture associated with hematopoietic stem cell transplantation (HSCT) could be assessed using the Fracture Risk Assessment Tool (FRAX), researchers from the University of Texas MD Anderson Cancer Center have found.

In a retrospective cohort study, Huifang Lu, MD, and her collaborators found that FRAX could predict the risk of fracture with reasonable accuracy. The area under the receiver operating characteristic curve was 0.66 for predicting a fracture 10 years after HSCT.

“Current guidelines recommend the evaluation of bone health at 1 year following the transplant, but we recommend that this needs to happen at a much earlier time,” Dr. Lu said at the European Congress of Rheumatology.

Determining how to assess risk earlier and prevent bone loss remains a challenge, however. FRAX is an easy and quick tool to use, but its predictive ability is modest, she said.

As the finding comes from a retrospective study, prospective evaluation of FRAX is needed in HSCT patients. If shown predictive in this setting, bone health could be assessed earlier using FRAX, ideally at or before the time of the transplant, to allow appropriate action to be taken, such as prescribing bisphosphonates to those identified to be at high risk.

There is no consensus on preventing and treating bone loss following HSCT, said Dr. Lu. In a meta-analysis performed by Dr. Lu and her associates (Bone Marrow Transplant. 2017;52[5]:663-70), less bone loss was seen in patients who received a bisphosphonate.

As the use of HSCT has expanded over the past two decades, there is an expanding population of survivors with potential long-term effects such as bone loss and a higher risk of fractures, compared with the general population, Dr. Lu explained.

The FRAX tool takes into account pre-HSCT factors such as age, smoking status, alcohol use, prior fracture, body mass index, and corticosteroid use. This can be considered in association with the fracture risk related to the various conditioning and supporting regimens that patients receive around the time of their transplants.

The study included 5,170 adult patients who had undergone HSCT at the University of Texas MD Anderson Cancer Center over a 10-year period. Patients were considered to have entered the cohort at the time of their transplants, Dr. Lu said. Their history of osteoporotic fractures up to 3.3 years later was obtained and verified by radiology and physician assessment. FRAX probabilities were then derived from baseline information.

The mean age of patients included was 52 years, 57% were male and 75% were white. One-quarter had experienced a prior fracture. Of note, 26% of the cohort underwent HSCT for multiple myeloma, 70% of whom had already had a fracture, compared with 9% of those who underwent HSCT for another reason such as leukemia or lymphoma.

Multivariate analyses were performed with and without considering death as a competing risk, and similar results were obtained. Higher FRAX scores (20 or greater) were more likely to be recorded in individuals who sustained a fracture than in those who did not. Patients who had an allogeneic HSCT were 15% more likely to have a fracture as those who received an autologous transplant. Perhaps not surprisingly, patients with multiple myeloma were more likely than those who had HSCT for other reasons to sustain a fracture by 10 years based on FRAX results (hazard ratio, 3.16).

Future research needs to look at the optimal cut offs for FRAX scores predictive of events and see if there is any association between the loss of bone and fracture risk. There also needs to be an evaluation of the use of concomitant medications and health economic analyses performed.

Dr. Lu had no conflicts of interest. The study was funded by the Rolanette and Berdon Lawrence Bone Disease Program of Texas and via Cancer Survivorship Research Seed Monday Grants from the University Cancer Foundation and Duncan Family Institute for Cancer Prevention and Risk Assessment to the University of Texas MD Anderson Cancer Center.

MADRID – The risk of osteoporotic fracture associated with hematopoietic stem cell transplantation (HSCT) could be assessed using the Fracture Risk Assessment Tool (FRAX), researchers from the University of Texas MD Anderson Cancer Center have found.

In a retrospective cohort study, Huifang Lu, MD, and her collaborators found that FRAX could predict the risk of fracture with reasonable accuracy. The area under the receiver operating characteristic curve was 0.66 for predicting a fracture 10 years after HSCT.

“Current guidelines recommend the evaluation of bone health at 1 year following the transplant, but we recommend that this needs to happen at a much earlier time,” Dr. Lu said at the European Congress of Rheumatology.

Determining how to assess risk earlier and prevent bone loss remains a challenge, however. FRAX is an easy and quick tool to use, but its predictive ability is modest, she said.

As the finding comes from a retrospective study, prospective evaluation of FRAX is needed in HSCT patients. If shown predictive in this setting, bone health could be assessed earlier using FRAX, ideally at or before the time of the transplant, to allow appropriate action to be taken, such as prescribing bisphosphonates to those identified to be at high risk.

There is no consensus on preventing and treating bone loss following HSCT, said Dr. Lu. In a meta-analysis performed by Dr. Lu and her associates (Bone Marrow Transplant. 2017;52[5]:663-70), less bone loss was seen in patients who received a bisphosphonate.

As the use of HSCT has expanded over the past two decades, there is an expanding population of survivors with potential long-term effects such as bone loss and a higher risk of fractures, compared with the general population, Dr. Lu explained.

The FRAX tool takes into account pre-HSCT factors such as age, smoking status, alcohol use, prior fracture, body mass index, and corticosteroid use. This can be considered in association with the fracture risk related to the various conditioning and supporting regimens that patients receive around the time of their transplants.

The study included 5,170 adult patients who had undergone HSCT at the University of Texas MD Anderson Cancer Center over a 10-year period. Patients were considered to have entered the cohort at the time of their transplants, Dr. Lu said. Their history of osteoporotic fractures up to 3.3 years later was obtained and verified by radiology and physician assessment. FRAX probabilities were then derived from baseline information.

The mean age of patients included was 52 years, 57% were male and 75% were white. One-quarter had experienced a prior fracture. Of note, 26% of the cohort underwent HSCT for multiple myeloma, 70% of whom had already had a fracture, compared with 9% of those who underwent HSCT for another reason such as leukemia or lymphoma.

Multivariate analyses were performed with and without considering death as a competing risk, and similar results were obtained. Higher FRAX scores (20 or greater) were more likely to be recorded in individuals who sustained a fracture than in those who did not. Patients who had an allogeneic HSCT were 15% more likely to have a fracture as those who received an autologous transplant. Perhaps not surprisingly, patients with multiple myeloma were more likely than those who had HSCT for other reasons to sustain a fracture by 10 years based on FRAX results (hazard ratio, 3.16).

Future research needs to look at the optimal cut offs for FRAX scores predictive of events and see if there is any association between the loss of bone and fracture risk. There also needs to be an evaluation of the use of concomitant medications and health economic analyses performed.

Dr. Lu had no conflicts of interest. The study was funded by the Rolanette and Berdon Lawrence Bone Disease Program of Texas and via Cancer Survivorship Research Seed Monday Grants from the University Cancer Foundation and Duncan Family Institute for Cancer Prevention and Risk Assessment to the University of Texas MD Anderson Cancer Center.

MADRID – Bisphosphonates mitigate the damaging effects of glucocorticoid on bone, boosting bone mineral density and reducing the risk of fracture by up to 33%, compared with placebo, according to a systematic review and meta-analysis.

The review of 11 randomized, controlled trials found that bisphosphonates consistently improved bone outcomes among patients taking prednisone, Anas Makhzoum, MD, said at the European Congress of Rheumatology.

[email protected]

On Twitter @alz_gal

MADRID – Bisphosphonates mitigate the damaging effects of glucocorticoid on bone, boosting bone mineral density and reducing the risk of fracture by up to 33%, compared with placebo, according to a systematic review and meta-analysis.

The review of 11 randomized, controlled trials found that bisphosphonates consistently improved bone outcomes among patients taking prednisone, Anas Makhzoum, MD, said at the European Congress of Rheumatology.

[email protected]

On Twitter @alz_gal

MADRID – Bisphosphonates mitigate the damaging effects of glucocorticoid on bone, boosting bone mineral density and reducing the risk of fracture by up to 33%, compared with placebo, according to a systematic review and meta-analysis.

The review of 11 randomized, controlled trials found that bisphosphonates consistently improved bone outcomes among patients taking prednisone, Anas Makhzoum, MD, said at the European Congress of Rheumatology.

[email protected]

On Twitter @alz_gal

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Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

NONESTROGEN PRODUCT FOR DYSPAREUNIA

FOR MORE INFORMATION, VISIT: http://www.amagpharma.com

ORAL MAINTENANCE TX FOR RECURRENT CANCER

FOR MORE INFORMATION, VISIT: http://www.zejula.com

MIGS STAPLING SYSTEM WITH REAL-TIME FEEDBACK

FOR MORE INFORMATION, VISIT: http://www.medtronic.com

BONE BUILDING AGENT

FOR MORE INFORMATION, VISIT: http://www.radiuspharm.com

PROTEOMIC BREAST CANCER ASSAY

FOR MORE INFORMATION, VISIT: http://www.provistadx.com

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

MADRID – In Sweden, less than 7% of those who experience an osteoporotic fracture receive osteoporosis treatment within the first year, when the risk of a second fracture is the highest.

Women are more likely than are men to get a prescription, but people older than 80 years, and those with dementia or low socioeconomic status, are less likely to receive one, Anna Spångeus, MD, PhD, said at the European Congress of Rheumatology.

[email protected]

On Twitter @alz_gal

MADRID – In Sweden, less than 7% of those who experience an osteoporotic fracture receive osteoporosis treatment within the first year, when the risk of a second fracture is the highest.

Women are more likely than are men to get a prescription, but people older than 80 years, and those with dementia or low socioeconomic status, are less likely to receive one, Anna Spångeus, MD, PhD, said at the European Congress of Rheumatology.

[email protected]

On Twitter @alz_gal

MADRID – In Sweden, less than 7% of those who experience an osteoporotic fracture receive osteoporosis treatment within the first year, when the risk of a second fracture is the highest.

Women are more likely than are men to get a prescription, but people older than 80 years, and those with dementia or low socioeconomic status, are less likely to receive one, Anna Spångeus, MD, PhD, said at the European Congress of Rheumatology.

[email protected]

On Twitter @alz_gal

MADRID – Romosozumab, an investigational bone-building agent, reduced new vertebral fractures by 73% among postmenopausal women with osteoporosis.

Compared with placebo, the monoclonal antibody also reduced the risk of a clinical fracture by 36% after 12 months of treatment, Piet Geusens, MD, said at the European Congress of Rheumatology. The effect was maintained at 24 months, with a 50% reduction in fracture risk, said Dr. Geusens of Maastricht University, the Netherlands.

Romosozumab also significantly reduced clinical and nonvertebral fractures and increased bone mineral density at the total hip, femoral neck, and lumbar spine in the phase III FRAME study, cosponsored by Amgen and UCB Pharma.

But recently, the finding of increased cardiovascular events in another highly anticipated phase III study of romosozumab cast a cloud of doubt over its rising star. During an interview at EULAR, a UCB company spokesman said the company no longer anticipates a 2017 Food and Drug Administration approval.

[email protected]

On Twitter @Alz_gal

MADRID – Romosozumab, an investigational bone-building agent, reduced new vertebral fractures by 73% among postmenopausal women with osteoporosis.

Compared with placebo, the monoclonal antibody also reduced the risk of a clinical fracture by 36% after 12 months of treatment, Piet Geusens, MD, said at the European Congress of Rheumatology. The effect was maintained at 24 months, with a 50% reduction in fracture risk, said Dr. Geusens of Maastricht University, the Netherlands.

Romosozumab also significantly reduced clinical and nonvertebral fractures and increased bone mineral density at the total hip, femoral neck, and lumbar spine in the phase III FRAME study, cosponsored by Amgen and UCB Pharma.

But recently, the finding of increased cardiovascular events in another highly anticipated phase III study of romosozumab cast a cloud of doubt over its rising star. During an interview at EULAR, a UCB company spokesman said the company no longer anticipates a 2017 Food and Drug Administration approval.

[email protected]

On Twitter @Alz_gal

MADRID – Romosozumab, an investigational bone-building agent, reduced new vertebral fractures by 73% among postmenopausal women with osteoporosis.

Compared with placebo, the monoclonal antibody also reduced the risk of a clinical fracture by 36% after 12 months of treatment, Piet Geusens, MD, said at the European Congress of Rheumatology. The effect was maintained at 24 months, with a 50% reduction in fracture risk, said Dr. Geusens of Maastricht University, the Netherlands.

Romosozumab also significantly reduced clinical and nonvertebral fractures and increased bone mineral density at the total hip, femoral neck, and lumbar spine in the phase III FRAME study, cosponsored by Amgen and UCB Pharma.

But recently, the finding of increased cardiovascular events in another highly anticipated phase III study of romosozumab cast a cloud of doubt over its rising star. During an interview at EULAR, a UCB company spokesman said the company no longer anticipates a 2017 Food and Drug Administration approval.

[email protected]

On Twitter @Alz_gal

VIENNA – A 6-week course of antibiotics, with an early switch from intravenous to oral, appears to be a safe and appropriate option for some patients with pyogenic vertebral osteomyelitis.

A single-center retrospective study of 82 such patients found two treatment failures and two deaths over 1 year (4.8% failure rate). The patients who died were very elderly with serious comorbidities. The two treatment failures occurred in patients with methicillin-resistant coagulase-negative staphylococcal infections of a central catheter.

“Only two of the failures were due to inadequate antibiotic treatment,” Adrien Lemaignen, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. “Both patients experienced a relapse of bacteremia with the same bacteria a few days after antibiotic cessation in a context of conservative treatment of a catheter-related infection.”

Guidelines recently adopted by the Infectious Diseases Society of America inspired the study, said Dr. Lemaignen of University Hospital of Tours, France. The 2015 document calls for 6-8 weeks of antibiotics, depending upon the infective organism and whether infective endocarditis complicates management. All suggested antibiotic regimens call for initial IV therapy followed by oral, but there are no cut-and-dried recommendations about when to switch. The guideline notes one study in which patients switched to oral after about 2.7 weeks, with a 97% success rate.

Dr. Lemaignen and his colleagues set out to determine cure rates of early oral relay in 82 patients with pyogenic vertebral osteomyelitis (PVO). All patients were treated at a single center from 2011 to 2016. The team defined treatment failure as death, or persistence or relapse of infection in the first year after treatment.

All patients had culture-proven PVO that also was visible on imaging. Patients were excluded if they had any brucellar, fungal, or mycobacterial coinfections, or if they had infected spinal implants.

The mean age of the patients in the cohort was 66 years; 39% had some neuropathology. The mean C-reactive protein level was 115 mg/L. More than half of the cases (56%) involved the lumbar-sacral spine; 30% were thoracic, and the remainder, cervical. About one-fifth had multiple level involvement. There was epidural inflammation in 68%, epidural abscess in 13%, and extradural abscess in 26%.

Staphylococcus aureus was the most common pathogen (34%); two infections were methicillin resistant. Other infective organisms were streptococci (27%), Gram-negative bacilli (15%), and coagulase-negative staph (12%). A few patients had enterococci (5%) or polymicrobial infections (7%).

Infective endocarditis was present in 16 patients; this was associated with enterococcal and streptococcal infections.

Treatment varied by pathogen. Patients with S. aureus received penicillin or cefazolin with an oral relay to fluoroquinolone/rifampicin or clindamycin. Those with streptococci received amoxicillin with or without an aminoglycoside, followed by oral amoxicillin or clindamycin. Those with coagulase-negative streptococci received a glycopeptide with or without blasticidin, followed by fluoroquinolone/rifampicin. Patients with enterococcal infections got a third generation cephalosporin followed by an oral third generation cephalosporin or a fluoroquinolone.

All but six patients received 6 weeks of treatment.

The mean oral relay occurred on day 12, but 30 patients (36%) were able to switch before 7 days elapsed. Thirteen patients had to stay on the IV route for their entire treatment; 25% of this group had infective endocarditis. Six patients, all of whom had motor symptoms, also needed surgery.

The median follow-up was 358 days. During this time, there were two deaths and two treatment failures.

One death was a 93-year-old who had a controlled sepsis, but died at day 79 of a massive hematemesis. The other was an 80-year-old with an amoxicillin-resistant staph infection and decompensated cirrhosis who died at day 49.

There were also two treatment failures. Both of these patients had methicillin-resistant coagulase-negative staph infections of indwelling central catheters. One had a relapse 70 days after the end of IV therapy; the other relapsed on day 26 of treatment, after a 2-week course of oral antibiotics.

Not all patients were able to succeed with 6 weeks of therapy. Three needed prolonged treatment: One of these had an infected vascular prosthesis and two were immunocompromised patients who had cervical osteomyelitis with multiple abscesses.

In light of these results, Dr. Lemaignen said, “We can say confirm the safety of short IV treatment with an early oral relay in pyogenic vertebral osteomyelitis under real-life conditions, with 95% success rate and good functional outcomes at 6 months.”

He had no relevant financial disclosures.
 

[email protected]

On Twitter @Alz_gal

VIENNA – A 6-week course of antibiotics, with an early switch from intravenous to oral, appears to be a safe and appropriate option for some patients with pyogenic vertebral osteomyelitis.

A single-center retrospective study of 82 such patients found two treatment failures and two deaths over 1 year (4.8% failure rate). The patients who died were very elderly with serious comorbidities. The two treatment failures occurred in patients with methicillin-resistant coagulase-negative staphylococcal infections of a central catheter.

“Only two of the failures were due to inadequate antibiotic treatment,” Adrien Lemaignen, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. “Both patients experienced a relapse of bacteremia with the same bacteria a few days after antibiotic cessation in a context of conservative treatment of a catheter-related infection.”

Guidelines recently adopted by the Infectious Diseases Society of America inspired the study, said Dr. Lemaignen of University Hospital of Tours, France. The 2015 document calls for 6-8 weeks of antibiotics, depending upon the infective organism and whether infective endocarditis complicates management. All suggested antibiotic regimens call for initial IV therapy followed by oral, but there are no cut-and-dried recommendations about when to switch. The guideline notes one study in which patients switched to oral after about 2.7 weeks, with a 97% success rate.

Dr. Lemaignen and his colleagues set out to determine cure rates of early oral relay in 82 patients with pyogenic vertebral osteomyelitis (PVO). All patients were treated at a single center from 2011 to 2016. The team defined treatment failure as death, or persistence or relapse of infection in the first year after treatment.

All patients had culture-proven PVO that also was visible on imaging. Patients were excluded if they had any brucellar, fungal, or mycobacterial coinfections, or if they had infected spinal implants.

The mean age of the patients in the cohort was 66 years; 39% had some neuropathology. The mean C-reactive protein level was 115 mg/L. More than half of the cases (56%) involved the lumbar-sacral spine; 30% were thoracic, and the remainder, cervical. About one-fifth had multiple level involvement. There was epidural inflammation in 68%, epidural abscess in 13%, and extradural abscess in 26%.

Staphylococcus aureus was the most common pathogen (34%); two infections were methicillin resistant. Other infective organisms were streptococci (27%), Gram-negative bacilli (15%), and coagulase-negative staph (12%). A few patients had enterococci (5%) or polymicrobial infections (7%).

Infective endocarditis was present in 16 patients; this was associated with enterococcal and streptococcal infections.

Treatment varied by pathogen. Patients with S. aureus received penicillin or cefazolin with an oral relay to fluoroquinolone/rifampicin or clindamycin. Those with streptococci received amoxicillin with or without an aminoglycoside, followed by oral amoxicillin or clindamycin. Those with coagulase-negative streptococci received a glycopeptide with or without blasticidin, followed by fluoroquinolone/rifampicin. Patients with enterococcal infections got a third generation cephalosporin followed by an oral third generation cephalosporin or a fluoroquinolone.

All but six patients received 6 weeks of treatment.

The mean oral relay occurred on day 12, but 30 patients (36%) were able to switch before 7 days elapsed. Thirteen patients had to stay on the IV route for their entire treatment; 25% of this group had infective endocarditis. Six patients, all of whom had motor symptoms, also needed surgery.

The median follow-up was 358 days. During this time, there were two deaths and two treatment failures.

One death was a 93-year-old who had a controlled sepsis, but died at day 79 of a massive hematemesis. The other was an 80-year-old with an amoxicillin-resistant staph infection and decompensated cirrhosis who died at day 49.

There were also two treatment failures. Both of these patients had methicillin-resistant coagulase-negative staph infections of indwelling central catheters. One had a relapse 70 days after the end of IV therapy; the other relapsed on day 26 of treatment, after a 2-week course of oral antibiotics.

Not all patients were able to succeed with 6 weeks of therapy. Three needed prolonged treatment: One of these had an infected vascular prosthesis and two were immunocompromised patients who had cervical osteomyelitis with multiple abscesses.

In light of these results, Dr. Lemaignen said, “We can say confirm the safety of short IV treatment with an early oral relay in pyogenic vertebral osteomyelitis under real-life conditions, with 95% success rate and good functional outcomes at 6 months.”

He had no relevant financial disclosures.
 

[email protected]

On Twitter @Alz_gal

VIENNA – A 6-week course of antibiotics, with an early switch from intravenous to oral, appears to be a safe and appropriate option for some patients with pyogenic vertebral osteomyelitis.

A single-center retrospective study of 82 such patients found two treatment failures and two deaths over 1 year (4.8% failure rate). The patients who died were very elderly with serious comorbidities. The two treatment failures occurred in patients with methicillin-resistant coagulase-negative staphylococcal infections of a central catheter.

“Only two of the failures were due to inadequate antibiotic treatment,” Adrien Lemaignen, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress. “Both patients experienced a relapse of bacteremia with the same bacteria a few days after antibiotic cessation in a context of conservative treatment of a catheter-related infection.”

Guidelines recently adopted by the Infectious Diseases Society of America inspired the study, said Dr. Lemaignen of University Hospital of Tours, France. The 2015 document calls for 6-8 weeks of antibiotics, depending upon the infective organism and whether infective endocarditis complicates management. All suggested antibiotic regimens call for initial IV therapy followed by oral, but there are no cut-and-dried recommendations about when to switch. The guideline notes one study in which patients switched to oral after about 2.7 weeks, with a 97% success rate.

Dr. Lemaignen and his colleagues set out to determine cure rates of early oral relay in 82 patients with pyogenic vertebral osteomyelitis (PVO). All patients were treated at a single center from 2011 to 2016. The team defined treatment failure as death, or persistence or relapse of infection in the first year after treatment.

All patients had culture-proven PVO that also was visible on imaging. Patients were excluded if they had any brucellar, fungal, or mycobacterial coinfections, or if they had infected spinal implants.

The mean age of the patients in the cohort was 66 years; 39% had some neuropathology. The mean C-reactive protein level was 115 mg/L. More than half of the cases (56%) involved the lumbar-sacral spine; 30% were thoracic, and the remainder, cervical. About one-fifth had multiple level involvement. There was epidural inflammation in 68%, epidural abscess in 13%, and extradural abscess in 26%.

Staphylococcus aureus was the most common pathogen (34%); two infections were methicillin resistant. Other infective organisms were streptococci (27%), Gram-negative bacilli (15%), and coagulase-negative staph (12%). A few patients had enterococci (5%) or polymicrobial infections (7%).

Infective endocarditis was present in 16 patients; this was associated with enterococcal and streptococcal infections.

Treatment varied by pathogen. Patients with S. aureus received penicillin or cefazolin with an oral relay to fluoroquinolone/rifampicin or clindamycin. Those with streptococci received amoxicillin with or without an aminoglycoside, followed by oral amoxicillin or clindamycin. Those with coagulase-negative streptococci received a glycopeptide with or without blasticidin, followed by fluoroquinolone/rifampicin. Patients with enterococcal infections got a third generation cephalosporin followed by an oral third generation cephalosporin or a fluoroquinolone.

All but six patients received 6 weeks of treatment.

The mean oral relay occurred on day 12, but 30 patients (36%) were able to switch before 7 days elapsed. Thirteen patients had to stay on the IV route for their entire treatment; 25% of this group had infective endocarditis. Six patients, all of whom had motor symptoms, also needed surgery.

The median follow-up was 358 days. During this time, there were two deaths and two treatment failures.

One death was a 93-year-old who had a controlled sepsis, but died at day 79 of a massive hematemesis. The other was an 80-year-old with an amoxicillin-resistant staph infection and decompensated cirrhosis who died at day 49.

There were also two treatment failures. Both of these patients had methicillin-resistant coagulase-negative staph infections of indwelling central catheters. One had a relapse 70 days after the end of IV therapy; the other relapsed on day 26 of treatment, after a 2-week course of oral antibiotics.

Not all patients were able to succeed with 6 weeks of therapy. Three needed prolonged treatment: One of these had an infected vascular prosthesis and two were immunocompromised patients who had cervical osteomyelitis with multiple abscesses.

In light of these results, Dr. Lemaignen said, “We can say confirm the safety of short IV treatment with an early oral relay in pyogenic vertebral osteomyelitis under real-life conditions, with 95% success rate and good functional outcomes at 6 months.”

He had no relevant financial disclosures.
 

[email protected]

On Twitter @Alz_gal

VIENNA – Two infusions of the long-acting lipoglycopeptide antibiotic dalbavancin showed a favorable clinical benefit for treatment of adult osteomyelitis in a phase II study.

Dalbavancin (Dalvance) showed positive results while avoiding the complexities of standard therapies that require longer, more frequent dosing, Urania Rappo, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Dalbavancin already is approved for acute bacterial skin and skin structure infections, and its long terminal half-life of 14 days and high bone penetration made it a natural candidate for evaluation in the treatment of osteomyelitis, said Dr. Rappo, director of clinical development (anti-infectives) at Allergan, which markets the drug and sponsored the study.

Michele G. Sullivan/Frontline Medical News

[email protected]

On Twitter @alz_gal

VIENNA – Two infusions of the long-acting lipoglycopeptide antibiotic dalbavancin showed a favorable clinical benefit for treatment of adult osteomyelitis in a phase II study.

Dalbavancin (Dalvance) showed positive results while avoiding the complexities of standard therapies that require longer, more frequent dosing, Urania Rappo, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Dalbavancin already is approved for acute bacterial skin and skin structure infections, and its long terminal half-life of 14 days and high bone penetration made it a natural candidate for evaluation in the treatment of osteomyelitis, said Dr. Rappo, director of clinical development (anti-infectives) at Allergan, which markets the drug and sponsored the study.

Michele G. Sullivan/Frontline Medical News

[email protected]

On Twitter @alz_gal

VIENNA – Two infusions of the long-acting lipoglycopeptide antibiotic dalbavancin showed a favorable clinical benefit for treatment of adult osteomyelitis in a phase II study.

Dalbavancin (Dalvance) showed positive results while avoiding the complexities of standard therapies that require longer, more frequent dosing, Urania Rappo, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.

Dalbavancin already is approved for acute bacterial skin and skin structure infections, and its long terminal half-life of 14 days and high bone penetration made it a natural candidate for evaluation in the treatment of osteomyelitis, said Dr. Rappo, director of clinical development (anti-infectives) at Allergan, which markets the drug and sponsored the study.

Michele G. Sullivan/Frontline Medical News

[email protected]

On Twitter @alz_gal

SAN FRANCISCO – Children were more likely to experience a fracture if they were prescribed antacids before age 1 year, according to a study of military families.

The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids. Similarly, children prescribed both PPIs and H₂ blockers before age 1 year were 31% more likely to have a fracture compared to those not taking the drugs.

“A lot of data are coming out that proton pump inhibitors are not quite as benign as we used to think, and we are seeing that fracture risk is increased with use,” U.S. Air Force Capt. Laura Malchodi, MD, a pediatrics resident at Walter Reed National Military Medical Center in Bethesda, Md., told colleagues at the Pediatric Academic Societies meeting.

Antacid use has been increasing among both adults and children, but the biggest rise has been in children under age 1 year, she said. Previous research into adult use of antacids has revealed an increased incidence of fractures, so Dr. Malchodi investigated the incidence of fractures in children under age 1 year among those who had taken PPIs, H₂ blockers, neither, or both.

“What this means for doctors is that when you do start to think of using proton pump inhibitors or any antacid therapy in children, we should really think of limiting it to one type if possible – H₂ blockers are now preferable – and for the shortest amount of time as possible,” Dr. Malchodi said of her findings.

The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years. Children who took antacids after age 1, spent more than a week in a neonatal intensive care unit, or had nonaccidental trauma (abuse) or osteogenesis imperfecta were excluded.

Ninety percent of the cohort had not received prescriptions for any antacids (789,631 children) in their first year of life, and 1.2% had received prescriptions for both PPIs and H₂ blockers before age 1 year. Of the remaining children, 7.7% had received prescriptions for H₂ blockers, and 0.8% for PPIs.

The children who had and had not been prescribed antacids were similar in median years enrolled in the system, but nearly twice as many who received antacid prescription had been preterm (6.4% vs. 3.5%, P less than .05). Similarly, 3.7% of those prescribed antacids had a low birth weight, compared with 2.2% of those not prescribed antacids (P less than .05). The median age of fracture also differed for the two groups: 3.9 years for those prescribed antacids and 4.5 years for those not (P less than .05).

In using medical records during their analysis, the researchers excluded follow-up visits for the same fracture within the previous 6 months. Before adjustment for covariates, boys had a slightly increased risk of fracture (hazard ratio [HR], 1.08), and those with a previous fracture had an 85% increased risk (HR, 1.85). Compared with children not prescribed antacids, those prescribed PPIs had a 23% increased risk of fracture (HR, 1.23), and those prescribed H₂ blockers had a 13% increased risk (HR, 1.13). Those prescribed combination antacid therapy had a 32% increased risk of fractures (HR, 1.32).

Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H₂ blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. For H₂ blockers, no statistically significant increased risk of fracture existed in those taking them before or after 6 months old.

Those taking PPIs, however, had a 25% increased risk of fracture if they took them before 6 months old, compared with a 20% increased risk if prescribed PPIs between 6 and 12 months. Likewise, children taking both PPIs and H₂ blockers before 6 months old had a 32% increased risk of fracture, compared with a 23% increased risk between 6 and 12 months old.

Analysis of the duration of children’s use of antacids revealed a dose-response relationship, with an increasing risk alongside increasing days taking the medication. For example, those on PPIs for a month or less had a 19% increased risk of fracture, compared with children not prescribed antacids, but that rose to a 23% increased risk for those taking PPIs from 60 to 150 days and to a 42% increased risk for taking them longer than 150 days.

Similarly, the risk of fracture after having taken H₂ blockers for up to a month was 14%, which increased to 22% for medication durations over 120 days. Children on combination therapy took the medication for much longer than did children prescribed either antacid. The risk of fracture was 17% greater for those taking them for up to 4 months, but that increased to a 50% greater risk for children taking both antacids for longer than 338 days.

“A couple of decades ago, we thought these medications were super safe, that there could be no problem with them,” Dr. Malchodi said, suggesting that their availability over the counter for adults may contribute to that perception. “With this growing evidence, there’s at least a lot more caution about using them,” she said.

Because the study relied on prescriptions for antacids, the researchers could not take into account which children actually took the antacids. Another limitation was their inability to consider other potential confounders, such as socioeconomic status or comorbidities that may later increase the risk of fracture. Further, exclusion of 6 months of follow-up after one fracture may have missed new fractures in that time period. Using a military cohort, on the other hand, meant having a geographically and socioeconomically diverse population with less risk of care bias because all the children had universal health care coverage.

No external funding was used. Dr. Malchodi reported having no disclosures.

*The View on the News was added on 6/13/17.

SAN FRANCISCO – Children were more likely to experience a fracture if they were prescribed antacids before age 1 year, according to a study of military families.

The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids. Similarly, children prescribed both PPIs and H₂ blockers before age 1 year were 31% more likely to have a fracture compared to those not taking the drugs.

“A lot of data are coming out that proton pump inhibitors are not quite as benign as we used to think, and we are seeing that fracture risk is increased with use,” U.S. Air Force Capt. Laura Malchodi, MD, a pediatrics resident at Walter Reed National Military Medical Center in Bethesda, Md., told colleagues at the Pediatric Academic Societies meeting.

Antacid use has been increasing among both adults and children, but the biggest rise has been in children under age 1 year, she said. Previous research into adult use of antacids has revealed an increased incidence of fractures, so Dr. Malchodi investigated the incidence of fractures in children under age 1 year among those who had taken PPIs, H₂ blockers, neither, or both.

“What this means for doctors is that when you do start to think of using proton pump inhibitors or any antacid therapy in children, we should really think of limiting it to one type if possible – H₂ blockers are now preferable – and for the shortest amount of time as possible,” Dr. Malchodi said of her findings.

The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years. Children who took antacids after age 1, spent more than a week in a neonatal intensive care unit, or had nonaccidental trauma (abuse) or osteogenesis imperfecta were excluded.

Ninety percent of the cohort had not received prescriptions for any antacids (789,631 children) in their first year of life, and 1.2% had received prescriptions for both PPIs and H₂ blockers before age 1 year. Of the remaining children, 7.7% had received prescriptions for H₂ blockers, and 0.8% for PPIs.

The children who had and had not been prescribed antacids were similar in median years enrolled in the system, but nearly twice as many who received antacid prescription had been preterm (6.4% vs. 3.5%, P less than .05). Similarly, 3.7% of those prescribed antacids had a low birth weight, compared with 2.2% of those not prescribed antacids (P less than .05). The median age of fracture also differed for the two groups: 3.9 years for those prescribed antacids and 4.5 years for those not (P less than .05).

In using medical records during their analysis, the researchers excluded follow-up visits for the same fracture within the previous 6 months. Before adjustment for covariates, boys had a slightly increased risk of fracture (hazard ratio [HR], 1.08), and those with a previous fracture had an 85% increased risk (HR, 1.85). Compared with children not prescribed antacids, those prescribed PPIs had a 23% increased risk of fracture (HR, 1.23), and those prescribed H₂ blockers had a 13% increased risk (HR, 1.13). Those prescribed combination antacid therapy had a 32% increased risk of fractures (HR, 1.32).

Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H₂ blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. For H₂ blockers, no statistically significant increased risk of fracture existed in those taking them before or after 6 months old.

Those taking PPIs, however, had a 25% increased risk of fracture if they took them before 6 months old, compared with a 20% increased risk if prescribed PPIs between 6 and 12 months. Likewise, children taking both PPIs and H₂ blockers before 6 months old had a 32% increased risk of fracture, compared with a 23% increased risk between 6 and 12 months old.

Analysis of the duration of children’s use of antacids revealed a dose-response relationship, with an increasing risk alongside increasing days taking the medication. For example, those on PPIs for a month or less had a 19% increased risk of fracture, compared with children not prescribed antacids, but that rose to a 23% increased risk for those taking PPIs from 60 to 150 days and to a 42% increased risk for taking them longer than 150 days.

Similarly, the risk of fracture after having taken H₂ blockers for up to a month was 14%, which increased to 22% for medication durations over 120 days. Children on combination therapy took the medication for much longer than did children prescribed either antacid. The risk of fracture was 17% greater for those taking them for up to 4 months, but that increased to a 50% greater risk for children taking both antacids for longer than 338 days.

“A couple of decades ago, we thought these medications were super safe, that there could be no problem with them,” Dr. Malchodi said, suggesting that their availability over the counter for adults may contribute to that perception. “With this growing evidence, there’s at least a lot more caution about using them,” she said.

Because the study relied on prescriptions for antacids, the researchers could not take into account which children actually took the antacids. Another limitation was their inability to consider other potential confounders, such as socioeconomic status or comorbidities that may later increase the risk of fracture. Further, exclusion of 6 months of follow-up after one fracture may have missed new fractures in that time period. Using a military cohort, on the other hand, meant having a geographically and socioeconomically diverse population with less risk of care bias because all the children had universal health care coverage.

No external funding was used. Dr. Malchodi reported having no disclosures.

*The View on the News was added on 6/13/17.

SAN FRANCISCO – Children were more likely to experience a fracture if they were prescribed antacids before age 1 year, according to a study of military families.

The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids. Similarly, children prescribed both PPIs and H₂ blockers before age 1 year were 31% more likely to have a fracture compared to those not taking the drugs.

“A lot of data are coming out that proton pump inhibitors are not quite as benign as we used to think, and we are seeing that fracture risk is increased with use,” U.S. Air Force Capt. Laura Malchodi, MD, a pediatrics resident at Walter Reed National Military Medical Center in Bethesda, Md., told colleagues at the Pediatric Academic Societies meeting.

Antacid use has been increasing among both adults and children, but the biggest rise has been in children under age 1 year, she said. Previous research into adult use of antacids has revealed an increased incidence of fractures, so Dr. Malchodi investigated the incidence of fractures in children under age 1 year among those who had taken PPIs, H₂ blockers, neither, or both.

“What this means for doctors is that when you do start to think of using proton pump inhibitors or any antacid therapy in children, we should really think of limiting it to one type if possible – H₂ blockers are now preferable – and for the shortest amount of time as possible,” Dr. Malchodi said of her findings.

The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years. Children who took antacids after age 1, spent more than a week in a neonatal intensive care unit, or had nonaccidental trauma (abuse) or osteogenesis imperfecta were excluded.

Ninety percent of the cohort had not received prescriptions for any antacids (789,631 children) in their first year of life, and 1.2% had received prescriptions for both PPIs and H₂ blockers before age 1 year. Of the remaining children, 7.7% had received prescriptions for H₂ blockers, and 0.8% for PPIs.

The children who had and had not been prescribed antacids were similar in median years enrolled in the system, but nearly twice as many who received antacid prescription had been preterm (6.4% vs. 3.5%, P less than .05). Similarly, 3.7% of those prescribed antacids had a low birth weight, compared with 2.2% of those not prescribed antacids (P less than .05). The median age of fracture also differed for the two groups: 3.9 years for those prescribed antacids and 4.5 years for those not (P less than .05).

In using medical records during their analysis, the researchers excluded follow-up visits for the same fracture within the previous 6 months. Before adjustment for covariates, boys had a slightly increased risk of fracture (hazard ratio [HR], 1.08), and those with a previous fracture had an 85% increased risk (HR, 1.85). Compared with children not prescribed antacids, those prescribed PPIs had a 23% increased risk of fracture (HR, 1.23), and those prescribed H₂ blockers had a 13% increased risk (HR, 1.13). Those prescribed combination antacid therapy had a 32% increased risk of fractures (HR, 1.32).

Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H₂ blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. For H₂ blockers, no statistically significant increased risk of fracture existed in those taking them before or after 6 months old.

Those taking PPIs, however, had a 25% increased risk of fracture if they took them before 6 months old, compared with a 20% increased risk if prescribed PPIs between 6 and 12 months. Likewise, children taking both PPIs and H₂ blockers before 6 months old had a 32% increased risk of fracture, compared with a 23% increased risk between 6 and 12 months old.

Analysis of the duration of children’s use of antacids revealed a dose-response relationship, with an increasing risk alongside increasing days taking the medication. For example, those on PPIs for a month or less had a 19% increased risk of fracture, compared with children not prescribed antacids, but that rose to a 23% increased risk for those taking PPIs from 60 to 150 days and to a 42% increased risk for taking them longer than 150 days.

Similarly, the risk of fracture after having taken H₂ blockers for up to a month was 14%, which increased to 22% for medication durations over 120 days. Children on combination therapy took the medication for much longer than did children prescribed either antacid. The risk of fracture was 17% greater for those taking them for up to 4 months, but that increased to a 50% greater risk for children taking both antacids for longer than 338 days.

“A couple of decades ago, we thought these medications were super safe, that there could be no problem with them,” Dr. Malchodi said, suggesting that their availability over the counter for adults may contribute to that perception. “With this growing evidence, there’s at least a lot more caution about using them,” she said.

Because the study relied on prescriptions for antacids, the researchers could not take into account which children actually took the antacids. Another limitation was their inability to consider other potential confounders, such as socioeconomic status or comorbidities that may later increase the risk of fracture. Further, exclusion of 6 months of follow-up after one fracture may have missed new fractures in that time period. Using a military cohort, on the other hand, meant having a geographically and socioeconomically diverse population with less risk of care bias because all the children had universal health care coverage.

No external funding was used. Dr. Malchodi reported having no disclosures.

*The View on the News was added on 6/13/17.

The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.

The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.

The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.

Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.

Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).

Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.

One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.

Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”

The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.

The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.

The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.

The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.

Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.

Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).

Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.

One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.

Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”

The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.

The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.

The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.

The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.

Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.

Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).

Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.

One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.

Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”

The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.

LAS VEGAS – Bisphosphonates may slow the onset and progression of osteoarthritis (OA), according to data from the National Institutes of Health–sponsored Osteoarthritis Initiative. “Bisphosphonates warrant further study as potential disease-modifying agents in osteoarthritis,” Tuhina Neogi, MD, declared in presenting the study findings at the World Congress on Osteoarthritis.

In addition to the promising signal of a preventive effect for bisphosphonates, her analysis of Osteoarthritis Initiative data yielded two other major findings: Changes over time in the MRI-based three-dimensional bone shape of the knee constitute a novel structural imaging biomarker that appears to be of value in monitoring patients with OA or at high risk for the joint disease, and bisphosphonate-induced suppression of bone turnover had no adverse long-term impact on osteoarthritis risk.

“While bisphosphonates may have beneficial articular cartilage effects, there are potential theoretical concerns regarding long-term effects of bone turnover. This issue hasn’t previously been addressed. Bone turnover suppression may lead to more bone deposition and bone stiffness, with adverse biomechanical consequences. But it did not appear, in this sample at least, that suppression of bone turnover had a negative impact over the long term,” said Dr. Neogi, professor of medicine at Boston University.

The Osteoarthritis Initiative is a multicenter, longitudinal, prospective, observational study of knee osteoarthritis launched by the NIH in 2002. Dr. Neogi’s analysis was limited to the 1,071 female participants free of radiographic knee OA at baseline and who had 3-Tesla MRIs of the right knee at baseline and annually thereafter for 4 years. They were at increased risk for OA on the basis of their age – a mean of 62 years – along with their mean body mass index of 28.3 kg/m2. Just under one-quarter of the women were on bisphosphonate therapy.

Prior studies of the effects of bisphosphonates in patients with knee OA have yielded conflicting results, in part because radiographic findings are a relatively crude indicator of bone and joint changes. 3D bone shape of the knee has been shown to change much more quickly than traditional radiographic measures. These changes predict the incidence of knee OA even years later, the rheumatologist explained at the congress sponsored by the Osteoarthritis Research Society International.

Using bone shape analytic software developed by England-based Imorphics, she and her coinvestigators categorized the women into three distinct groups on the basis of the trajectory of MRI changes toward a more osteoarthritic bone shape over time. Of them, 23% fell into the fast-change group, 49% were in the intermediate group, and 28% were in the slowest-changing group. The rate of MRI bone shape progression toward knee OA was 2.7-times higher in the fastest, compared with the slowest, group.

The incidence of radiographic OA during 4 years of prospective follow-up was 14% in the fastest bone shape-changing group, 8% in the intermediate-speed group, and 4% in the slowest-changing group.

In a multivariate analysis adjusted for age, BMI, education, race, quadriceps strength, and history of knee injury, bisphosphonate users were 41% less likely to be in the fastest bone shape–changing group and 32% less likely to be in the intermediate group, compared with the slowest-changing group.

As a rheumatologist with a PhD in epidemiology, Dr. Neogi was readily prepared to critique her own study. The major limitation in her view was the potential for residual confounding, which is inherent in observational studies. In this instance, the possibility of confounding by indication cannot be excluded. Also, bone mineral density data wasn’t collected in the Osteoarthritis Initiative. Future studies should evaluate the impact over time of new-onset bisphosphonate therapy as a means of altering the slope of the trajectory of MRI-based 3D bone shape of the knee, Dr. Neogi said.

She reported having no financial conflicts regarding the NIH-sponsored study.

[email protected]

LAS VEGAS – Bisphosphonates may slow the onset and progression of osteoarthritis (OA), according to data from the National Institutes of Health–sponsored Osteoarthritis Initiative. “Bisphosphonates warrant further study as potential disease-modifying agents in osteoarthritis,” Tuhina Neogi, MD, declared in presenting the study findings at the World Congress on Osteoarthritis.

In addition to the promising signal of a preventive effect for bisphosphonates, her analysis of Osteoarthritis Initiative data yielded two other major findings: Changes over time in the MRI-based three-dimensional bone shape of the knee constitute a novel structural imaging biomarker that appears to be of value in monitoring patients with OA or at high risk for the joint disease, and bisphosphonate-induced suppression of bone turnover had no adverse long-term impact on osteoarthritis risk.

“While bisphosphonates may have beneficial articular cartilage effects, there are potential theoretical concerns regarding long-term effects of bone turnover. This issue hasn’t previously been addressed. Bone turnover suppression may lead to more bone deposition and bone stiffness, with adverse biomechanical consequences. But it did not appear, in this sample at least, that suppression of bone turnover had a negative impact over the long term,” said Dr. Neogi, professor of medicine at Boston University.

The Osteoarthritis Initiative is a multicenter, longitudinal, prospective, observational study of knee osteoarthritis launched by the NIH in 2002. Dr. Neogi’s analysis was limited to the 1,071 female participants free of radiographic knee OA at baseline and who had 3-Tesla MRIs of the right knee at baseline and annually thereafter for 4 years. They were at increased risk for OA on the basis of their age – a mean of 62 years – along with their mean body mass index of 28.3 kg/m2. Just under one-quarter of the women were on bisphosphonate therapy.

Prior studies of the effects of bisphosphonates in patients with knee OA have yielded conflicting results, in part because radiographic findings are a relatively crude indicator of bone and joint changes. 3D bone shape of the knee has been shown to change much more quickly than traditional radiographic measures. These changes predict the incidence of knee OA even years later, the rheumatologist explained at the congress sponsored by the Osteoarthritis Research Society International.

Using bone shape analytic software developed by England-based Imorphics, she and her coinvestigators categorized the women into three distinct groups on the basis of the trajectory of MRI changes toward a more osteoarthritic bone shape over time. Of them, 23% fell into the fast-change group, 49% were in the intermediate group, and 28% were in the slowest-changing group. The rate of MRI bone shape progression toward knee OA was 2.7-times higher in the fastest, compared with the slowest, group.

The incidence of radiographic OA during 4 years of prospective follow-up was 14% in the fastest bone shape-changing group, 8% in the intermediate-speed group, and 4% in the slowest-changing group.

In a multivariate analysis adjusted for age, BMI, education, race, quadriceps strength, and history of knee injury, bisphosphonate users were 41% less likely to be in the fastest bone shape–changing group and 32% less likely to be in the intermediate group, compared with the slowest-changing group.

As a rheumatologist with a PhD in epidemiology, Dr. Neogi was readily prepared to critique her own study. The major limitation in her view was the potential for residual confounding, which is inherent in observational studies. In this instance, the possibility of confounding by indication cannot be excluded. Also, bone mineral density data wasn’t collected in the Osteoarthritis Initiative. Future studies should evaluate the impact over time of new-onset bisphosphonate therapy as a means of altering the slope of the trajectory of MRI-based 3D bone shape of the knee, Dr. Neogi said.

She reported having no financial conflicts regarding the NIH-sponsored study.

[email protected]

LAS VEGAS – Bisphosphonates may slow the onset and progression of osteoarthritis (OA), according to data from the National Institutes of Health–sponsored Osteoarthritis Initiative. “Bisphosphonates warrant further study as potential disease-modifying agents in osteoarthritis,” Tuhina Neogi, MD, declared in presenting the study findings at the World Congress on Osteoarthritis.

In addition to the promising signal of a preventive effect for bisphosphonates, her analysis of Osteoarthritis Initiative data yielded two other major findings: Changes over time in the MRI-based three-dimensional bone shape of the knee constitute a novel structural imaging biomarker that appears to be of value in monitoring patients with OA or at high risk for the joint disease, and bisphosphonate-induced suppression of bone turnover had no adverse long-term impact on osteoarthritis risk.

“While bisphosphonates may have beneficial articular cartilage effects, there are potential theoretical concerns regarding long-term effects of bone turnover. This issue hasn’t previously been addressed. Bone turnover suppression may lead to more bone deposition and bone stiffness, with adverse biomechanical consequences. But it did not appear, in this sample at least, that suppression of bone turnover had a negative impact over the long term,” said Dr. Neogi, professor of medicine at Boston University.

The Osteoarthritis Initiative is a multicenter, longitudinal, prospective, observational study of knee osteoarthritis launched by the NIH in 2002. Dr. Neogi’s analysis was limited to the 1,071 female participants free of radiographic knee OA at baseline and who had 3-Tesla MRIs of the right knee at baseline and annually thereafter for 4 years. They were at increased risk for OA on the basis of their age – a mean of 62 years – along with their mean body mass index of 28.3 kg/m2. Just under one-quarter of the women were on bisphosphonate therapy.

Prior studies of the effects of bisphosphonates in patients with knee OA have yielded conflicting results, in part because radiographic findings are a relatively crude indicator of bone and joint changes. 3D bone shape of the knee has been shown to change much more quickly than traditional radiographic measures. These changes predict the incidence of knee OA even years later, the rheumatologist explained at the congress sponsored by the Osteoarthritis Research Society International.

Using bone shape analytic software developed by England-based Imorphics, she and her coinvestigators categorized the women into three distinct groups on the basis of the trajectory of MRI changes toward a more osteoarthritic bone shape over time. Of them, 23% fell into the fast-change group, 49% were in the intermediate group, and 28% were in the slowest-changing group. The rate of MRI bone shape progression toward knee OA was 2.7-times higher in the fastest, compared with the slowest, group.

The incidence of radiographic OA during 4 years of prospective follow-up was 14% in the fastest bone shape-changing group, 8% in the intermediate-speed group, and 4% in the slowest-changing group.

In a multivariate analysis adjusted for age, BMI, education, race, quadriceps strength, and history of knee injury, bisphosphonate users were 41% less likely to be in the fastest bone shape–changing group and 32% less likely to be in the intermediate group, compared with the slowest-changing group.

As a rheumatologist with a PhD in epidemiology, Dr. Neogi was readily prepared to critique her own study. The major limitation in her view was the potential for residual confounding, which is inherent in observational studies. In this instance, the possibility of confounding by indication cannot be excluded. Also, bone mineral density data wasn’t collected in the Osteoarthritis Initiative. Future studies should evaluate the impact over time of new-onset bisphosphonate therapy as a means of altering the slope of the trajectory of MRI-based 3D bone shape of the knee, Dr. Neogi said.

She reported having no financial conflicts regarding the NIH-sponsored study.

[email protected]