Bruce Jancin

SAN DIEGO – Postmenopausal women who are being treated for low bone mineral density have nearly a fivefold greater response rate to bisphosphonate therapy if they maintain a serum vitamin D level of 33 ng/mL or higher than they do with a level below that threshold, according to an award-winning study.

Moreover, a multivariate analysis demonstrated that for each 1-ng/mL decrease in serum vitamin D level, the likelihood of a favorable response to bisphosphonate therapy dropped by 5%, Dr. Amanda Carmel reported at the annual meeting of the American Society for Bone and Mineral Research.

This is the first study to identify a threshold level of serum vitamin D that defines improved therapeutic outcomes with bisphosphonates. The identified threshold of 33 ng/mL is higher than recommended as adequate for the general population in the 2010 Institute of Medicine report. The discrepancy suggests that higher vitamin D levels may be required for specific therapeutic outcomes, said Dr. Carmel, whose study earned the 2011 ASBMR Shun-Ichi Harada Young Investigator Award.

The study was based upon a chart review of 210 women (mean age, 66 years) who had been on bisphosphonate therapy for low bone mass or osteoporosis for an average of 5 years. Half were on alendronate (Fosamax), 27% were on risedronate (Actonel), and the rest were on ibandronate (Boniva) or zoledronic acid (Reclast).

In all, 52% of subjects were categorized as bisphosphonate nonresponders on the basis of a T score less than –3 that persisted on dual-energy x-ray absorptiometry scans taken at least 18 months apart, or a greater-than-3% decrease in bone mineral density, or an incident fracture on therapy.

The average serum vitamin D level was 42.1 ng/mL in responders and 32.3% in nonresponders. A level of 33 ng/mL or less was present in 21% of responders and 58% of nonresponders, said Dr. Carmel of Cornell University, New York.

Several audience members expressed skepticism regarding her conclusions. They argued that Dr. Carmel may have mistaken cause and effect. In their view, the most likely explanation for nonresponse to bisphosphonates is poor adherence to medication, and women who are noncompliant with their bisphosphonate are also probably going to be nonadherent to their vitamin D supplementation.

Dr. Carmel replied that she and her colleagues screened for poor compliance by asking women if they were taking their bisphosphonate regularly and excluding those who said they weren’t.

She reported having no financial conflicts.

SAN DIEGO – Postmenopausal women who are being treated for low bone mineral density have nearly a fivefold greater response rate to bisphosphonate therapy if they maintain a serum vitamin D level of 33 ng/mL or higher than they do with a level below that threshold, according to an award-winning study.

Moreover, a multivariate analysis demonstrated that for each 1-ng/mL decrease in serum vitamin D level, the likelihood of a favorable response to bisphosphonate therapy dropped by 5%, Dr. Amanda Carmel reported at the annual meeting of the American Society for Bone and Mineral Research.

This is the first study to identify a threshold level of serum vitamin D that defines improved therapeutic outcomes with bisphosphonates. The identified threshold of 33 ng/mL is higher than recommended as adequate for the general population in the 2010 Institute of Medicine report. The discrepancy suggests that higher vitamin D levels may be required for specific therapeutic outcomes, said Dr. Carmel, whose study earned the 2011 ASBMR Shun-Ichi Harada Young Investigator Award.

The study was based upon a chart review of 210 women (mean age, 66 years) who had been on bisphosphonate therapy for low bone mass or osteoporosis for an average of 5 years. Half were on alendronate (Fosamax), 27% were on risedronate (Actonel), and the rest were on ibandronate (Boniva) or zoledronic acid (Reclast).

In all, 52% of subjects were categorized as bisphosphonate nonresponders on the basis of a T score less than –3 that persisted on dual-energy x-ray absorptiometry scans taken at least 18 months apart, or a greater-than-3% decrease in bone mineral density, or an incident fracture on therapy.

The average serum vitamin D level was 42.1 ng/mL in responders and 32.3% in nonresponders. A level of 33 ng/mL or less was present in 21% of responders and 58% of nonresponders, said Dr. Carmel of Cornell University, New York.

Several audience members expressed skepticism regarding her conclusions. They argued that Dr. Carmel may have mistaken cause and effect. In their view, the most likely explanation for nonresponse to bisphosphonates is poor adherence to medication, and women who are noncompliant with their bisphosphonate are also probably going to be nonadherent to their vitamin D supplementation.

Dr. Carmel replied that she and her colleagues screened for poor compliance by asking women if they were taking their bisphosphonate regularly and excluding those who said they weren’t.

She reported having no financial conflicts.

SAN DIEGO – Postmenopausal women who are being treated for low bone mineral density have nearly a fivefold greater response rate to bisphosphonate therapy if they maintain a serum vitamin D level of 33 ng/mL or higher than they do with a level below that threshold, according to an award-winning study.

Moreover, a multivariate analysis demonstrated that for each 1-ng/mL decrease in serum vitamin D level, the likelihood of a favorable response to bisphosphonate therapy dropped by 5%, Dr. Amanda Carmel reported at the annual meeting of the American Society for Bone and Mineral Research.

This is the first study to identify a threshold level of serum vitamin D that defines improved therapeutic outcomes with bisphosphonates. The identified threshold of 33 ng/mL is higher than recommended as adequate for the general population in the 2010 Institute of Medicine report. The discrepancy suggests that higher vitamin D levels may be required for specific therapeutic outcomes, said Dr. Carmel, whose study earned the 2011 ASBMR Shun-Ichi Harada Young Investigator Award.

The study was based upon a chart review of 210 women (mean age, 66 years) who had been on bisphosphonate therapy for low bone mass or osteoporosis for an average of 5 years. Half were on alendronate (Fosamax), 27% were on risedronate (Actonel), and the rest were on ibandronate (Boniva) or zoledronic acid (Reclast).

In all, 52% of subjects were categorized as bisphosphonate nonresponders on the basis of a T score less than –3 that persisted on dual-energy x-ray absorptiometry scans taken at least 18 months apart, or a greater-than-3% decrease in bone mineral density, or an incident fracture on therapy.

The average serum vitamin D level was 42.1 ng/mL in responders and 32.3% in nonresponders. A level of 33 ng/mL or less was present in 21% of responders and 58% of nonresponders, said Dr. Carmel of Cornell University, New York.

Several audience members expressed skepticism regarding her conclusions. They argued that Dr. Carmel may have mistaken cause and effect. In their view, the most likely explanation for nonresponse to bisphosphonates is poor adherence to medication, and women who are noncompliant with their bisphosphonate are also probably going to be nonadherent to their vitamin D supplementation.

Dr. Carmel replied that she and her colleagues screened for poor compliance by asking women if they were taking their bisphosphonate regularly and excluding those who said they weren’t.

She reported having no financial conflicts.

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the meeting.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation “might improve convenience and compliance with calcitonin therapy,” observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analogue of human calcitonin that's 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin. This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impacts on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year. In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia.

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the meeting.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation “might improve convenience and compliance with calcitonin therapy,” observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analogue of human calcitonin that's 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin. This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impacts on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year. In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia.

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the meeting.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation “might improve convenience and compliance with calcitonin therapy,” observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analogue of human calcitonin that's 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin. This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impacts on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year. In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia.

SAN DIEGO – The risk of hip fracture nearly doubles in the week following a new prescription for a loop diuretic.

In contrast, there is no spike in the risk of hip fracture in the 7 days after a new prescription for other classes of diuretics or for ACE inhibitors, according to an analysis of the Health Improvement Network (THIN) database involving more than 400 U.K. primary care practices.

The short-term jump in risk of hip fracture may be related to the prominent urinary symptoms that often accompany a new prescription for loop diuretics. The resultant rush to the bathroom could increase falls during that initial adjustment period, Dr. Sarah D. Berry speculated.

She reported on 28,703 subjects who experienced a hip fracture and more than 2 million others who did not. She and her coworkers compared the occurrence of new diuretic prescriptions in the 7 days prior to a hip fracture to the occurrence of new diuretic prescriptions in the control period 31–37 days before the fracture.

The adjusted odds ratio of an incident hip fracture was significantly increased by 80% in the 7 days following a new prescription for a loop diuretic. The absolute risk during this week-long window, however, remained low: 2.9 hip fractures per 100,000 new loop diuretic prescriptions, said Dr. Berry of the Hebrew SeniorLife Institute for Aging Research and Beth Israel Deaconess Medical Center, Boston.

Dr. Berry declared having no financial conflicts regarding the study, which was supported by the National Institutes of Health and Hebrew SeniorLife.

SAN DIEGO – The risk of hip fracture nearly doubles in the week following a new prescription for a loop diuretic.

In contrast, there is no spike in the risk of hip fracture in the 7 days after a new prescription for other classes of diuretics or for ACE inhibitors, according to an analysis of the Health Improvement Network (THIN) database involving more than 400 U.K. primary care practices.

The short-term jump in risk of hip fracture may be related to the prominent urinary symptoms that often accompany a new prescription for loop diuretics. The resultant rush to the bathroom could increase falls during that initial adjustment period, Dr. Sarah D. Berry speculated.

She reported on 28,703 subjects who experienced a hip fracture and more than 2 million others who did not. She and her coworkers compared the occurrence of new diuretic prescriptions in the 7 days prior to a hip fracture to the occurrence of new diuretic prescriptions in the control period 31–37 days before the fracture.

The adjusted odds ratio of an incident hip fracture was significantly increased by 80% in the 7 days following a new prescription for a loop diuretic. The absolute risk during this week-long window, however, remained low: 2.9 hip fractures per 100,000 new loop diuretic prescriptions, said Dr. Berry of the Hebrew SeniorLife Institute for Aging Research and Beth Israel Deaconess Medical Center, Boston.

Dr. Berry declared having no financial conflicts regarding the study, which was supported by the National Institutes of Health and Hebrew SeniorLife.

SAN DIEGO – The risk of hip fracture nearly doubles in the week following a new prescription for a loop diuretic.

In contrast, there is no spike in the risk of hip fracture in the 7 days after a new prescription for other classes of diuretics or for ACE inhibitors, according to an analysis of the Health Improvement Network (THIN) database involving more than 400 U.K. primary care practices.

The short-term jump in risk of hip fracture may be related to the prominent urinary symptoms that often accompany a new prescription for loop diuretics. The resultant rush to the bathroom could increase falls during that initial adjustment period, Dr. Sarah D. Berry speculated.

She reported on 28,703 subjects who experienced a hip fracture and more than 2 million others who did not. She and her coworkers compared the occurrence of new diuretic prescriptions in the 7 days prior to a hip fracture to the occurrence of new diuretic prescriptions in the control period 31–37 days before the fracture.

The adjusted odds ratio of an incident hip fracture was significantly increased by 80% in the 7 days following a new prescription for a loop diuretic. The absolute risk during this week-long window, however, remained low: 2.9 hip fractures per 100,000 new loop diuretic prescriptions, said Dr. Berry of the Hebrew SeniorLife Institute for Aging Research and Beth Israel Deaconess Medical Center, Boston.

Dr. Berry declared having no financial conflicts regarding the study, which was supported by the National Institutes of Health and Hebrew SeniorLife.

Major Finding: New osteoporotic fractures occurred in 1.6% of men on zoledronic acid and in 4.9% of those on placebo after 2 years of either active treatment or placebo.

Data Source: Multinational, randomized, phase III clinical trial of 1,199 men with primary or secondary osteoporosis.

Disclosures: Dr. Boonen disclosed that he has received research grants from and serves as a consultant to Novartis.

San Diego – Once-yearly intravenous zoledronic acid in men who have osteoporosis reduced their risk of vertebral fractures by 67% over a 2-year period, compared with placebo, in a large, multinational, phase III randomized clinical trial.

“This is the first clear demonstration of antifracture efficacy for an osteoporosis agent in male osteoporosis,” said Dr. Steven Boonen in presenting the study results at the meeting.

“These findings suggest the use of zoledronic acid as a treatment option in male patients, particularly because annual infusions ensure that patients will have the full effect of treatment for at least the next year,” added Dr. Boonen, who is professor of geriatric medicine and head of the gerontology and geriatrics section at Catholic University of Leuven (Belgium).

He reported on 1,199 men (mean age, 66 years) with primary osteoporosis or osteoporosis secondary to hypogonadism who were randomized in a double-blind fashion to a once-yearly 15-minute infusion of 5 mg of zoledronic acid (Reclast) or placebo at 134 centers. At enrollment, 32% of the men had one or more vertebral fractures.

The primary end point of the study was the proportion of subjects with one or more new vertebral fractures during 2 years of follow-up. The rate was 1.6% in men assigned to zoledronic acid and 4.9% in the placebo-treated controls, which translated to a highly significant 67% relative risk reduction. The 12-month rate was 0.9% in the zoledronic acid group vs. 2.8% in controls, for a 68% relative risk reduction.

The incidence of moderate to severe vertebral fractures was similarly reduced by 63% in zoledronic acid recipients, compared with controls.

Men on zoledronic acid had a stable 60% reduction in levels of the bone turnover biomarker CTx, compared with the placebo group, throughout the study, Dr. Boonen said.

At 2 years, bone mineral density was roughly 6% greater at the spine and 2% greater at the total hip in the patients who received zoledronic acid, compared with the controls.

“All of these findings are remarkably similar in magnitude to the risk reductions that have been documented with zoledronic acid in the pivotal fracture trial in postmenopausal osteoporosis,” the geriatrician observed.

The men on zoledronic acid also experienced a smaller height loss, compared with controls (mean, 2.34 vs. 4.49 mm), he said.

No major safety issues arose in the study. Similar numbers of patients in both study arms dropped out of the trial because of adverse events.

At the present time, zoledronic acid's approved indications include treatment to increase bone mass in men with osteoporosis.

Bone mineral density was roughly 6% greater at the spine in the zoledronic acid group.

Source DR. BOONEN

Major Finding: New osteoporotic fractures occurred in 1.6% of men on zoledronic acid and in 4.9% of those on placebo after 2 years of either active treatment or placebo.

Data Source: Multinational, randomized, phase III clinical trial of 1,199 men with primary or secondary osteoporosis.

Disclosures: Dr. Boonen disclosed that he has received research grants from and serves as a consultant to Novartis.

San Diego – Once-yearly intravenous zoledronic acid in men who have osteoporosis reduced their risk of vertebral fractures by 67% over a 2-year period, compared with placebo, in a large, multinational, phase III randomized clinical trial.

“This is the first clear demonstration of antifracture efficacy for an osteoporosis agent in male osteoporosis,” said Dr. Steven Boonen in presenting the study results at the meeting.

“These findings suggest the use of zoledronic acid as a treatment option in male patients, particularly because annual infusions ensure that patients will have the full effect of treatment for at least the next year,” added Dr. Boonen, who is professor of geriatric medicine and head of the gerontology and geriatrics section at Catholic University of Leuven (Belgium).

He reported on 1,199 men (mean age, 66 years) with primary osteoporosis or osteoporosis secondary to hypogonadism who were randomized in a double-blind fashion to a once-yearly 15-minute infusion of 5 mg of zoledronic acid (Reclast) or placebo at 134 centers. At enrollment, 32% of the men had one or more vertebral fractures.

The primary end point of the study was the proportion of subjects with one or more new vertebral fractures during 2 years of follow-up. The rate was 1.6% in men assigned to zoledronic acid and 4.9% in the placebo-treated controls, which translated to a highly significant 67% relative risk reduction. The 12-month rate was 0.9% in the zoledronic acid group vs. 2.8% in controls, for a 68% relative risk reduction.

The incidence of moderate to severe vertebral fractures was similarly reduced by 63% in zoledronic acid recipients, compared with controls.

Men on zoledronic acid had a stable 60% reduction in levels of the bone turnover biomarker CTx, compared with the placebo group, throughout the study, Dr. Boonen said.

At 2 years, bone mineral density was roughly 6% greater at the spine and 2% greater at the total hip in the patients who received zoledronic acid, compared with the controls.

“All of these findings are remarkably similar in magnitude to the risk reductions that have been documented with zoledronic acid in the pivotal fracture trial in postmenopausal osteoporosis,” the geriatrician observed.

The men on zoledronic acid also experienced a smaller height loss, compared with controls (mean, 2.34 vs. 4.49 mm), he said.

No major safety issues arose in the study. Similar numbers of patients in both study arms dropped out of the trial because of adverse events.

At the present time, zoledronic acid's approved indications include treatment to increase bone mass in men with osteoporosis.

Bone mineral density was roughly 6% greater at the spine in the zoledronic acid group.

Source DR. BOONEN

Major Finding: New osteoporotic fractures occurred in 1.6% of men on zoledronic acid and in 4.9% of those on placebo after 2 years of either active treatment or placebo.

Data Source: Multinational, randomized, phase III clinical trial of 1,199 men with primary or secondary osteoporosis.

Disclosures: Dr. Boonen disclosed that he has received research grants from and serves as a consultant to Novartis.

San Diego – Once-yearly intravenous zoledronic acid in men who have osteoporosis reduced their risk of vertebral fractures by 67% over a 2-year period, compared with placebo, in a large, multinational, phase III randomized clinical trial.

“This is the first clear demonstration of antifracture efficacy for an osteoporosis agent in male osteoporosis,” said Dr. Steven Boonen in presenting the study results at the meeting.

“These findings suggest the use of zoledronic acid as a treatment option in male patients, particularly because annual infusions ensure that patients will have the full effect of treatment for at least the next year,” added Dr. Boonen, who is professor of geriatric medicine and head of the gerontology and geriatrics section at Catholic University of Leuven (Belgium).

He reported on 1,199 men (mean age, 66 years) with primary osteoporosis or osteoporosis secondary to hypogonadism who were randomized in a double-blind fashion to a once-yearly 15-minute infusion of 5 mg of zoledronic acid (Reclast) or placebo at 134 centers. At enrollment, 32% of the men had one or more vertebral fractures.

The primary end point of the study was the proportion of subjects with one or more new vertebral fractures during 2 years of follow-up. The rate was 1.6% in men assigned to zoledronic acid and 4.9% in the placebo-treated controls, which translated to a highly significant 67% relative risk reduction. The 12-month rate was 0.9% in the zoledronic acid group vs. 2.8% in controls, for a 68% relative risk reduction.

The incidence of moderate to severe vertebral fractures was similarly reduced by 63% in zoledronic acid recipients, compared with controls.

Men on zoledronic acid had a stable 60% reduction in levels of the bone turnover biomarker CTx, compared with the placebo group, throughout the study, Dr. Boonen said.

At 2 years, bone mineral density was roughly 6% greater at the spine and 2% greater at the total hip in the patients who received zoledronic acid, compared with the controls.

“All of these findings are remarkably similar in magnitude to the risk reductions that have been documented with zoledronic acid in the pivotal fracture trial in postmenopausal osteoporosis,” the geriatrician observed.

The men on zoledronic acid also experienced a smaller height loss, compared with controls (mean, 2.34 vs. 4.49 mm), he said.

No major safety issues arose in the study. Similar numbers of patients in both study arms dropped out of the trial because of adverse events.

At the present time, zoledronic acid's approved indications include treatment to increase bone mass in men with osteoporosis.

Bone mineral density was roughly 6% greater at the spine in the zoledronic acid group.

Source DR. BOONEN

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic. The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants, she noted.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up. It's likely that reduced mobility and increased risk of falling play an important role in the pathogenesis of fractures in obese postmenopausal women, although this is an issue that needs further study, she observed.

In a separate presentation, Helena Johansson presented an analysis of BMI and fracture risk in 281,637 women drawn from 27 prospective, population-based cohort studies that were conducted in more than two dozen countries. The women were aged 20–105 years (mean age, 63 years).

A total of 18,441 osteoporotic fractures occurred in the study population during a mean 4.8 years of follow-up. After adjustment for bone mineral density, obesity proved to be a risk factor for fracture. For example, women with a BMI of 34 had an adjusted 14% increased risk of osteoporotic fracture, compared with those having a BMI of 26, an elevation in risk that, while modest, was statistically significant. And women having a BMI of 34 had a more impressive adjusted 60% increased risk of humerus or elbow fracture, added Ms. Johansson, a statistician at the University of Gothenburg (Sweden).

Dr. Compston declared having no relevant financial disclosures. GLOW is supported by grants from Sanofi-Aventis and Warner Chilcott. Ms. Johansson declared having no relevant financial disclosures.

Only 27% of obese GLOW participants with incident fractures were placed on bone-protective medication.

Source DR. COMPSTON

Incident fractures of the ankle and tibia were significantly more common in obese women.

Source ©Living Art Enterprises, LLC / Photo Researchers, Inc

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic. The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants, she noted.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up. It's likely that reduced mobility and increased risk of falling play an important role in the pathogenesis of fractures in obese postmenopausal women, although this is an issue that needs further study, she observed.

In a separate presentation, Helena Johansson presented an analysis of BMI and fracture risk in 281,637 women drawn from 27 prospective, population-based cohort studies that were conducted in more than two dozen countries. The women were aged 20–105 years (mean age, 63 years).

A total of 18,441 osteoporotic fractures occurred in the study population during a mean 4.8 years of follow-up. After adjustment for bone mineral density, obesity proved to be a risk factor for fracture. For example, women with a BMI of 34 had an adjusted 14% increased risk of osteoporotic fracture, compared with those having a BMI of 26, an elevation in risk that, while modest, was statistically significant. And women having a BMI of 34 had a more impressive adjusted 60% increased risk of humerus or elbow fracture, added Ms. Johansson, a statistician at the University of Gothenburg (Sweden).

Dr. Compston declared having no relevant financial disclosures. GLOW is supported by grants from Sanofi-Aventis and Warner Chilcott. Ms. Johansson declared having no relevant financial disclosures.

Only 27% of obese GLOW participants with incident fractures were placed on bone-protective medication.

Source DR. COMPSTON

Incident fractures of the ankle and tibia were significantly more common in obese women.

Source ©Living Art Enterprises, LLC / Photo Researchers, Inc

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic. The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants, she noted.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up. It's likely that reduced mobility and increased risk of falling play an important role in the pathogenesis of fractures in obese postmenopausal women, although this is an issue that needs further study, she observed.

In a separate presentation, Helena Johansson presented an analysis of BMI and fracture risk in 281,637 women drawn from 27 prospective, population-based cohort studies that were conducted in more than two dozen countries. The women were aged 20–105 years (mean age, 63 years).

A total of 18,441 osteoporotic fractures occurred in the study population during a mean 4.8 years of follow-up. After adjustment for bone mineral density, obesity proved to be a risk factor for fracture. For example, women with a BMI of 34 had an adjusted 14% increased risk of osteoporotic fracture, compared with those having a BMI of 26, an elevation in risk that, while modest, was statistically significant. And women having a BMI of 34 had a more impressive adjusted 60% increased risk of humerus or elbow fracture, added Ms. Johansson, a statistician at the University of Gothenburg (Sweden).

Dr. Compston declared having no relevant financial disclosures. GLOW is supported by grants from Sanofi-Aventis and Warner Chilcott. Ms. Johansson declared having no relevant financial disclosures.

Only 27% of obese GLOW participants with incident fractures were placed on bone-protective medication.

Source DR. COMPSTON

Incident fractures of the ankle and tibia were significantly more common in obese women.

Source ©Living Art Enterprises, LLC / Photo Researchers, Inc

Major Finding: Vitamin D deficiency was associated with a 3.3-fold increased likelihood of CAC being present at 3 years after adjusting statistically for age, gender, and hours of exposure to daylight.

Data Source: 374 type 1 diabetes patients with a mean age of 40 years in the CACTI study.

Disclosures: The CACTI study was funded by the National Institutes of Health. Dr. Rewers declared having no relevant financial interests.

KEYSTONE, COLO. – Vitamin D deficiency strongly predicted rapid progression of coronary artery calcification in adults with type 1 diabetes in a large, prospective study.

The association between low vitamin D and progression of coronary artery calcification was independent of the standard coronary artery disease risk factors. This suggests vitamin D may be related to early coronary atherosclerosis through a novel pathway, Dr. Marian Rewers observed at the conference, sponsored by the University of Colorado and the Children's Diabetes Foundation at Denver.

The findings came from the prospective CACTI (Coronary Artery Calcification in Type 1 Diabetes) study. This portion of CACTI included 374 type 1 diabetes patients with a mean age of 40 years. More than half were women. Coronary artery calcification (CAC) was measured by electron-beam CT at baseline and 3- and 6-year follow-up. Serum 25-hydroxyvitamin D was measured at the 3-year mark.

One-quarter of the subjects had insufficient vitamin D – a serum level of 20–30 ng/mL. Another 10% were vitamin D deficient. Deficiency was associated with a 3.3-fold increased likelihood of CAC at 3 years after adjustment for age, gender, and hours of exposure to daylight. Patients with vitamin D insufficiency had an adjusted significant 1.8-fold increased risk, said Dr. Rewers, principal investigator for CACTI.

Among subjects who were free of CAC at the 3 years, vitamin D deficiency predicted development of CAC between years 3 and 6 of follow-up. A novel finding in CACTI was that vitamin D deficiency at 3 years was a significant predictor of developing CAC during the next 3 years only in the subgroup with the vitamin D receptor M1T CC genotype. Vitamin D deficiency in patients with the CC genotype was associated with a 6.5-fold increased likelihood of CAC, compared with that of subjects with a normal vitamin D level.

In contrast, vitamin D deficient patients with the CT or TT genotypes weren't at significantly increased risk, noted Dr. Rewers, professor of pediatrics and preventive medicine, and clinical director of the Barbara Davis Center for Childhood Diabetes at the university.

CAC is a well-established marker of arterial plaque burden and a strong predictor of future coronary events. The CACTI findings suggest vitamin D may be involved in the early stages of CAC.

Audience members asked Dr. Rewers and other speakers how much vitamin D they're taking.

“Every time I come home from a medical meeting I take more vitamin D,” quipped Dr. David M. Kendall, chief scientific and medical officer for the American Diabetes Association and a diabetologist at the University of Minnesota, Minneapolis. He was referring to evidence suggesting benefits ranging from cardioprotection to anticancer and antidementia effects and beyond.

Like Dr. Kendall, Dr. Matthew C. Riddle now takes 2,000 mg of vitamin D daily.

“We don't know the answer as to the 'right' amount. But the risk vs. benefit is appealing. There are some real potential benefits,” said Dr. Riddle, professor of medicine at Oregon Health & Science University, Portland.

Vitamin D may be related to early coronary atherosclerosis through a novel pathway.

Source DR. REWERS

Major Finding: Vitamin D deficiency was associated with a 3.3-fold increased likelihood of CAC being present at 3 years after adjusting statistically for age, gender, and hours of exposure to daylight.

Data Source: 374 type 1 diabetes patients with a mean age of 40 years in the CACTI study.

Disclosures: The CACTI study was funded by the National Institutes of Health. Dr. Rewers declared having no relevant financial interests.

KEYSTONE, COLO. – Vitamin D deficiency strongly predicted rapid progression of coronary artery calcification in adults with type 1 diabetes in a large, prospective study.

The association between low vitamin D and progression of coronary artery calcification was independent of the standard coronary artery disease risk factors. This suggests vitamin D may be related to early coronary atherosclerosis through a novel pathway, Dr. Marian Rewers observed at the conference, sponsored by the University of Colorado and the Children's Diabetes Foundation at Denver.

The findings came from the prospective CACTI (Coronary Artery Calcification in Type 1 Diabetes) study. This portion of CACTI included 374 type 1 diabetes patients with a mean age of 40 years. More than half were women. Coronary artery calcification (CAC) was measured by electron-beam CT at baseline and 3- and 6-year follow-up. Serum 25-hydroxyvitamin D was measured at the 3-year mark.

One-quarter of the subjects had insufficient vitamin D – a serum level of 20–30 ng/mL. Another 10% were vitamin D deficient. Deficiency was associated with a 3.3-fold increased likelihood of CAC at 3 years after adjustment for age, gender, and hours of exposure to daylight. Patients with vitamin D insufficiency had an adjusted significant 1.8-fold increased risk, said Dr. Rewers, principal investigator for CACTI.

Among subjects who were free of CAC at the 3 years, vitamin D deficiency predicted development of CAC between years 3 and 6 of follow-up. A novel finding in CACTI was that vitamin D deficiency at 3 years was a significant predictor of developing CAC during the next 3 years only in the subgroup with the vitamin D receptor M1T CC genotype. Vitamin D deficiency in patients with the CC genotype was associated with a 6.5-fold increased likelihood of CAC, compared with that of subjects with a normal vitamin D level.

In contrast, vitamin D deficient patients with the CT or TT genotypes weren't at significantly increased risk, noted Dr. Rewers, professor of pediatrics and preventive medicine, and clinical director of the Barbara Davis Center for Childhood Diabetes at the university.

CAC is a well-established marker of arterial plaque burden and a strong predictor of future coronary events. The CACTI findings suggest vitamin D may be involved in the early stages of CAC.

Audience members asked Dr. Rewers and other speakers how much vitamin D they're taking.

“Every time I come home from a medical meeting I take more vitamin D,” quipped Dr. David M. Kendall, chief scientific and medical officer for the American Diabetes Association and a diabetologist at the University of Minnesota, Minneapolis. He was referring to evidence suggesting benefits ranging from cardioprotection to anticancer and antidementia effects and beyond.

Like Dr. Kendall, Dr. Matthew C. Riddle now takes 2,000 mg of vitamin D daily.

“We don't know the answer as to the 'right' amount. But the risk vs. benefit is appealing. There are some real potential benefits,” said Dr. Riddle, professor of medicine at Oregon Health & Science University, Portland.

Vitamin D may be related to early coronary atherosclerosis through a novel pathway.

Source DR. REWERS

Major Finding: Vitamin D deficiency was associated with a 3.3-fold increased likelihood of CAC being present at 3 years after adjusting statistically for age, gender, and hours of exposure to daylight.

Data Source: 374 type 1 diabetes patients with a mean age of 40 years in the CACTI study.

Disclosures: The CACTI study was funded by the National Institutes of Health. Dr. Rewers declared having no relevant financial interests.

KEYSTONE, COLO. – Vitamin D deficiency strongly predicted rapid progression of coronary artery calcification in adults with type 1 diabetes in a large, prospective study.

The association between low vitamin D and progression of coronary artery calcification was independent of the standard coronary artery disease risk factors. This suggests vitamin D may be related to early coronary atherosclerosis through a novel pathway, Dr. Marian Rewers observed at the conference, sponsored by the University of Colorado and the Children's Diabetes Foundation at Denver.

The findings came from the prospective CACTI (Coronary Artery Calcification in Type 1 Diabetes) study. This portion of CACTI included 374 type 1 diabetes patients with a mean age of 40 years. More than half were women. Coronary artery calcification (CAC) was measured by electron-beam CT at baseline and 3- and 6-year follow-up. Serum 25-hydroxyvitamin D was measured at the 3-year mark.

One-quarter of the subjects had insufficient vitamin D – a serum level of 20–30 ng/mL. Another 10% were vitamin D deficient. Deficiency was associated with a 3.3-fold increased likelihood of CAC at 3 years after adjustment for age, gender, and hours of exposure to daylight. Patients with vitamin D insufficiency had an adjusted significant 1.8-fold increased risk, said Dr. Rewers, principal investigator for CACTI.

Among subjects who were free of CAC at the 3 years, vitamin D deficiency predicted development of CAC between years 3 and 6 of follow-up. A novel finding in CACTI was that vitamin D deficiency at 3 years was a significant predictor of developing CAC during the next 3 years only in the subgroup with the vitamin D receptor M1T CC genotype. Vitamin D deficiency in patients with the CC genotype was associated with a 6.5-fold increased likelihood of CAC, compared with that of subjects with a normal vitamin D level.

In contrast, vitamin D deficient patients with the CT or TT genotypes weren't at significantly increased risk, noted Dr. Rewers, professor of pediatrics and preventive medicine, and clinical director of the Barbara Davis Center for Childhood Diabetes at the university.

CAC is a well-established marker of arterial plaque burden and a strong predictor of future coronary events. The CACTI findings suggest vitamin D may be involved in the early stages of CAC.

Audience members asked Dr. Rewers and other speakers how much vitamin D they're taking.

“Every time I come home from a medical meeting I take more vitamin D,” quipped Dr. David M. Kendall, chief scientific and medical officer for the American Diabetes Association and a diabetologist at the University of Minnesota, Minneapolis. He was referring to evidence suggesting benefits ranging from cardioprotection to anticancer and antidementia effects and beyond.

Like Dr. Kendall, Dr. Matthew C. Riddle now takes 2,000 mg of vitamin D daily.

“We don't know the answer as to the 'right' amount. But the risk vs. benefit is appealing. There are some real potential benefits,” said Dr. Riddle, professor of medicine at Oregon Health & Science University, Portland.

Vitamin D may be related to early coronary atherosclerosis through a novel pathway.

Source DR. REWERS

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the meeting.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation “might improve convenience and compliance with calcitonin therapy,” observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analog of human calcitonin that's 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin.

This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impact on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, estimates at least 2 million American women have discontinued osteoporosis treatment. The company plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year. In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia. A double-blind Phase II trial is underway.

Dr. Binkley disclosed he has received a research grant from Tarsa, which sponsored the Phase III trial.

An oral formulation 'might improve convenience and compliance with calcitonin therapy.'

Source DR. BINKLEY

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the meeting.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation “might improve convenience and compliance with calcitonin therapy,” observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analog of human calcitonin that's 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin.

This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impact on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, estimates at least 2 million American women have discontinued osteoporosis treatment. The company plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year. In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia. A double-blind Phase II trial is underway.

Dr. Binkley disclosed he has received a research grant from Tarsa, which sponsored the Phase III trial.

An oral formulation 'might improve convenience and compliance with calcitonin therapy.'

Source DR. BINKLEY

SAN DIEGO – A novel once-daily oral calcitonin tablet hit all of its efficacy and safety end points in a phase III clinical trial for treatment of postmenopausal osteoporosis.

The oral formulation of recombinant salmon calcitonin, known as Ostora, proved significantly more effective at building bone mineral density than conventional nasal calcitonin in the 18-site, multinational, double-blind, double-placebo ORACAL trial, Dr. Neil Binkley reported at the meeting.

ORACAL involved 565 postmenopausal women with osteoporosis and a mean age of 66 years. They were randomized 4:3:2 to once-daily bedtime therapy with oral calcitonin at 200 mcg, conventional nasal calcitonin at 200 IU, or placebo.

The absolute change in lumbar spine bone mineral density at 48 weeks – the primary study end point – showed a relatively modest 1.5% increase in the oral calcitonin group. But this was significantly greater than the 0.8% increase with the commercially available nasal calcitonin, which in turn was significantly better than the placebo response.

Potential safety issues with the bisphosphonates and other currently available medications have led many osteoporosis patients to decline therapy, while other women stop treatment due to side effects. Calcitonin, in contrast, has a 30-year history of safe prescription use via the intranasal and injectable routes. An oral formulation “might improve convenience and compliance with calcitonin therapy,” observed Dr. Binkley, an endocrinologist at the University of Wisconsin, Madison.

Salmon calcitonin is an analog of human calcitonin that's 30- to 50-fold more potent in suppressing osteoclast resorption.

In the ORACAL trial, levels of CTx (C-terminal telopeptide), a biomarker of bone resorption, dropped by 30% in the oral calcitonin group at 48 weeks, compared with 11% reductions in the nasal calcitonin and placebo arms.

Only 6.5% of women assigned to oral calcitonin developed anticalcitonin antibodies, compared with 32.5% of those on nasal calcitonin.

This suggests delivery of the agent via the gastrointestinal tract is less immunogenic than the nasal mucosa. In any case, the production of antibodies had no apparent impact on safety or efficacy, the endocrinologist continued.

The side effect picture in the oral and nasal calcitonin groups mirrored that in placebo-treated controls.

Tarsa Therapeutics, which is developing oral calcitonin, estimates at least 2 million American women have discontinued osteoporosis treatment. The company plans to file with the Food and Drug Administration for marketing approval later this year and with the European regulatory agency next year. In addition, the company is developing oral calcitonin for the prevention of osteoporosis in postmenopausal women with osteopenia. A double-blind Phase II trial is underway.

Dr. Binkley disclosed he has received a research grant from Tarsa, which sponsored the Phase III trial.

An oral formulation 'might improve convenience and compliance with calcitonin therapy.'

Source DR. BINKLEY

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic. The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up. It's likely that reduced mobility and increased risk of falling play an important role in the pathogenesis of fractures in obese postmenopausal women, although this is an issue that needs further study, she observed.

In a separate presentation, Helena Johansson presented an analysis of BMI and fracture risk in 281,637 women drawn from 27 prospective, population-based cohort studies that were conducted in more than two dozen countries. The women were aged 20–105 years (mean age, 63 years).

A total of 18,441 osteoporotic fractures occurred in the study population during a mean 4.8 years of follow-up. After adjustment for bone mineral density, obesity proved to be a risk factor for fracture.

For example, women with a BMI of 34 had an adjusted 14% increased risk of osteoporotic fracture, compared with those having a BMI of 26, an elevation in risk that, while modest, was statistically significant.

And women having a BMI of 34 had a more impressive adjusted 60% increased risk of humerus or elbow fracture, added Ms. Johansson, a statistician at the University of Gothenburg (Sweden).

Dr. Compston declared having no relevant financial disclosures. GLOW is supported by grants from Sanofi-Aventis and Warner Chilcott.

Ms. Johansson declared having no relevant financial disclosures.

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic. The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up. It's likely that reduced mobility and increased risk of falling play an important role in the pathogenesis of fractures in obese postmenopausal women, although this is an issue that needs further study, she observed.

In a separate presentation, Helena Johansson presented an analysis of BMI and fracture risk in 281,637 women drawn from 27 prospective, population-based cohort studies that were conducted in more than two dozen countries. The women were aged 20–105 years (mean age, 63 years).

A total of 18,441 osteoporotic fractures occurred in the study population during a mean 4.8 years of follow-up. After adjustment for bone mineral density, obesity proved to be a risk factor for fracture.

For example, women with a BMI of 34 had an adjusted 14% increased risk of osteoporotic fracture, compared with those having a BMI of 26, an elevation in risk that, while modest, was statistically significant.

And women having a BMI of 34 had a more impressive adjusted 60% increased risk of humerus or elbow fracture, added Ms. Johansson, a statistician at the University of Gothenburg (Sweden).

Dr. Compston declared having no relevant financial disclosures. GLOW is supported by grants from Sanofi-Aventis and Warner Chilcott.

Ms. Johansson declared having no relevant financial disclosures.

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic. The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up. It's likely that reduced mobility and increased risk of falling play an important role in the pathogenesis of fractures in obese postmenopausal women, although this is an issue that needs further study, she observed.

In a separate presentation, Helena Johansson presented an analysis of BMI and fracture risk in 281,637 women drawn from 27 prospective, population-based cohort studies that were conducted in more than two dozen countries. The women were aged 20–105 years (mean age, 63 years).

A total of 18,441 osteoporotic fractures occurred in the study population during a mean 4.8 years of follow-up. After adjustment for bone mineral density, obesity proved to be a risk factor for fracture.

For example, women with a BMI of 34 had an adjusted 14% increased risk of osteoporotic fracture, compared with those having a BMI of 26, an elevation in risk that, while modest, was statistically significant.

And women having a BMI of 34 had a more impressive adjusted 60% increased risk of humerus or elbow fracture, added Ms. Johansson, a statistician at the University of Gothenburg (Sweden).

Dr. Compston declared having no relevant financial disclosures. GLOW is supported by grants from Sanofi-Aventis and Warner Chilcott.

Ms. Johansson declared having no relevant financial disclosures.

Major Finding: New osteoporotic fractures occurred in 1.6% of men on zoledronic acid and in 4.9% of those on placebo after 2 years of either active treatment or placebo.

Data Source: Multinational, randomized, phase III clinical trial of 1,199 men with primary or secondary osteoporosis.

Disclosures: Dr. Boonen disclosed that he has received research grants from and serves as a consultant to Novartis.

DENVER – Once-yearly intravenous zoledronic acid in men with osteoporosis reduced their risk of vertebral fractures by 67% over 2 years, compared with placebo, in a large, multinational, phase III, randomized clinical trial.

“This is the first clear demonstration of antifracture efficacy for an osteoporosis agent in male osteoporosis,” said Dr. Steven Boonen in presenting the study results at the meeting.

“These findings suggest the use of zoledronic acid as a treatment option in male patients, particularly because annual infusions ensure that patients will have the full effect of treatment for at least the next year,” added Dr. Boonen, professor of geriatric medicine and head of the gerontology and geriatrics section at Catholic University of Leuven (Belgium).

He reported on 1,199 men (mean age, 66 years) with primary osteoporosis or osteoporosis secondary to hypogonadism who were randomized in a double-blind fashion to a once-yearly 15-minute infusion of 5 mg of zoledronic acid (Reclast) or placebo at 134 centers.

At enrollment, 32% of the men had one or more vertebral fractures.

The primary study end point was the proportion of subjects with one or more new vertebral fractures during 2 years of follow-up.

The rate was 1.6% in men assigned to zoledronic acid and 4.9% in placebo-treated controls, which translated to a highly significant 67% relative risk reduction.

The 12-month rate was 0.9% in the zoledronic acid group vs. 2.8% in controls, for a 68% relative risk reduction, Dr. Boonen reported.

The incidence of moderate to severe vertebral fractures was similarly reduced by 63% in zoledronic acid recipients, compared with controls.

Men on zoledronic acid had a stable 60% reduction in levels of the bone turnover biomarker CTx, compared with the placebo group, throughout the study.

At 2 years, bone mineral density was roughly 6% greater at the spine and 2% greater at the total hip in the zoledronic acid group, compared with controls, he said.

“All of these findings are remarkably similar in magnitude to the risk reductions that have been documented with zoledronic acid in the pivotal fracture trial in postmenopausal osteoporosis,” the geriatrician observed.

Men on zoledronic acid also experienced a smaller height loss, compared with controls (mean, 2.34 vs. 4.49 mm).

No major safety issues arose in the study. Similar numbers of patients in both study arms dropped out of the trial because of adverse events, Dr. Boonen reported.

At present, zoledronic acid's approved indications include treatment to increase bone mass in men with osteoporosis.

Bone mineral density was roughly 6% greater at the spine in the zoledronic acid group.

Source DR. BOONEN

Major Finding: New osteoporotic fractures occurred in 1.6% of men on zoledronic acid and in 4.9% of those on placebo after 2 years of either active treatment or placebo.

Data Source: Multinational, randomized, phase III clinical trial of 1,199 men with primary or secondary osteoporosis.

Disclosures: Dr. Boonen disclosed that he has received research grants from and serves as a consultant to Novartis.

DENVER – Once-yearly intravenous zoledronic acid in men with osteoporosis reduced their risk of vertebral fractures by 67% over 2 years, compared with placebo, in a large, multinational, phase III, randomized clinical trial.

“This is the first clear demonstration of antifracture efficacy for an osteoporosis agent in male osteoporosis,” said Dr. Steven Boonen in presenting the study results at the meeting.

“These findings suggest the use of zoledronic acid as a treatment option in male patients, particularly because annual infusions ensure that patients will have the full effect of treatment for at least the next year,” added Dr. Boonen, professor of geriatric medicine and head of the gerontology and geriatrics section at Catholic University of Leuven (Belgium).

He reported on 1,199 men (mean age, 66 years) with primary osteoporosis or osteoporosis secondary to hypogonadism who were randomized in a double-blind fashion to a once-yearly 15-minute infusion of 5 mg of zoledronic acid (Reclast) or placebo at 134 centers.

At enrollment, 32% of the men had one or more vertebral fractures.

The primary study end point was the proportion of subjects with one or more new vertebral fractures during 2 years of follow-up.

The rate was 1.6% in men assigned to zoledronic acid and 4.9% in placebo-treated controls, which translated to a highly significant 67% relative risk reduction.

The 12-month rate was 0.9% in the zoledronic acid group vs. 2.8% in controls, for a 68% relative risk reduction, Dr. Boonen reported.

The incidence of moderate to severe vertebral fractures was similarly reduced by 63% in zoledronic acid recipients, compared with controls.

Men on zoledronic acid had a stable 60% reduction in levels of the bone turnover biomarker CTx, compared with the placebo group, throughout the study.

At 2 years, bone mineral density was roughly 6% greater at the spine and 2% greater at the total hip in the zoledronic acid group, compared with controls, he said.

“All of these findings are remarkably similar in magnitude to the risk reductions that have been documented with zoledronic acid in the pivotal fracture trial in postmenopausal osteoporosis,” the geriatrician observed.

Men on zoledronic acid also experienced a smaller height loss, compared with controls (mean, 2.34 vs. 4.49 mm).

No major safety issues arose in the study. Similar numbers of patients in both study arms dropped out of the trial because of adverse events, Dr. Boonen reported.

At present, zoledronic acid's approved indications include treatment to increase bone mass in men with osteoporosis.

Bone mineral density was roughly 6% greater at the spine in the zoledronic acid group.

Source DR. BOONEN

Major Finding: New osteoporotic fractures occurred in 1.6% of men on zoledronic acid and in 4.9% of those on placebo after 2 years of either active treatment or placebo.

Data Source: Multinational, randomized, phase III clinical trial of 1,199 men with primary or secondary osteoporosis.

Disclosures: Dr. Boonen disclosed that he has received research grants from and serves as a consultant to Novartis.

DENVER – Once-yearly intravenous zoledronic acid in men with osteoporosis reduced their risk of vertebral fractures by 67% over 2 years, compared with placebo, in a large, multinational, phase III, randomized clinical trial.

“This is the first clear demonstration of antifracture efficacy for an osteoporosis agent in male osteoporosis,” said Dr. Steven Boonen in presenting the study results at the meeting.

“These findings suggest the use of zoledronic acid as a treatment option in male patients, particularly because annual infusions ensure that patients will have the full effect of treatment for at least the next year,” added Dr. Boonen, professor of geriatric medicine and head of the gerontology and geriatrics section at Catholic University of Leuven (Belgium).

He reported on 1,199 men (mean age, 66 years) with primary osteoporosis or osteoporosis secondary to hypogonadism who were randomized in a double-blind fashion to a once-yearly 15-minute infusion of 5 mg of zoledronic acid (Reclast) or placebo at 134 centers.

At enrollment, 32% of the men had one or more vertebral fractures.

The primary study end point was the proportion of subjects with one or more new vertebral fractures during 2 years of follow-up.

The rate was 1.6% in men assigned to zoledronic acid and 4.9% in placebo-treated controls, which translated to a highly significant 67% relative risk reduction.

The 12-month rate was 0.9% in the zoledronic acid group vs. 2.8% in controls, for a 68% relative risk reduction, Dr. Boonen reported.

The incidence of moderate to severe vertebral fractures was similarly reduced by 63% in zoledronic acid recipients, compared with controls.

Men on zoledronic acid had a stable 60% reduction in levels of the bone turnover biomarker CTx, compared with the placebo group, throughout the study.

At 2 years, bone mineral density was roughly 6% greater at the spine and 2% greater at the total hip in the zoledronic acid group, compared with controls, he said.

“All of these findings are remarkably similar in magnitude to the risk reductions that have been documented with zoledronic acid in the pivotal fracture trial in postmenopausal osteoporosis,” the geriatrician observed.

Men on zoledronic acid also experienced a smaller height loss, compared with controls (mean, 2.34 vs. 4.49 mm).

No major safety issues arose in the study. Similar numbers of patients in both study arms dropped out of the trial because of adverse events, Dr. Boonen reported.

At present, zoledronic acid's approved indications include treatment to increase bone mass in men with osteoporosis.

Bone mineral density was roughly 6% greater at the spine in the zoledronic acid group.

Source DR. BOONEN

Major Finding: The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese, compared with 7.3% in the underweight group.

Data Source: A study of 44,534 postmenopausal women in the United States and nine other countries who are participating in the ongoing prospective observational GLOW study.

Disclosures: The GLOW study is supported by grants from Sanofi-Aventis and Warner Chilcott. Dr. Compston declared having no relevant financial disclosures.

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic.

The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up.

Obese women with an incident fracture had much higher rates of diabetes, asthma, and emphysema.

Source DR. COMPSTON

Major Finding: The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese, compared with 7.3% in the underweight group.

Data Source: A study of 44,534 postmenopausal women in the United States and nine other countries who are participating in the ongoing prospective observational GLOW study.

Disclosures: The GLOW study is supported by grants from Sanofi-Aventis and Warner Chilcott. Dr. Compston declared having no relevant financial disclosures.

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic.

The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up.

Obese women with an incident fracture had much higher rates of diabetes, asthma, and emphysema.

Source DR. COMPSTON

Major Finding: The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese, compared with 7.3% in the underweight group.

Data Source: A study of 44,534 postmenopausal women in the United States and nine other countries who are participating in the ongoing prospective observational GLOW study.

Disclosures: The GLOW study is supported by grants from Sanofi-Aventis and Warner Chilcott. Dr. Compston declared having no relevant financial disclosures.

DENVER – New data indicate that obesity in postmenopausal women doesn't protect against fractures, contrary to the conventional wisdom.

Indeed, postmenopausal obesity actually appears to be a risk factor for fractures at selected sites, Dr. Juliet E. Compston reported at the meeting.

This is a finding with major public health implications because of the growing obesity epidemic.

The ramifications are especially pressing in light of new evidence that obese postmenopausal women who experience a fracture are far less likely than nonobese women to be placed on bone-protective medication, said Dr. Compston, professor of bone medicine at the University of Cambridge (England).

She reported on a study of 44,534 postmenopausal women (mean age, 67 years) in the United States and nine other countries who are participating in the ongoing, prospective, observational GLOW (Global Longitudinal Study of Osteoporosis in Women). At enrollment, 23.4% of the women had a body mass index of 30 kg/m

The prevalence of fracture at baseline was 23% in obese women, 24% in nonobese women, and 32% in the underweight study population. The incidence of one or more new fractures during 2 years of follow-up was 6.4% in the obese and similar at 6.8% in the nonobese women, compared with 7.3% in the underweight group.

Thus, nearly one in four postmenopausal women with a fracture is obese. As the obesity rate continues to climb in the developed world, fractures in the obese will increasingly contribute to the overall burden of fractures in the postmenopausal population, Dr. Compston observed.

The higher prevalence and incidence of fracture in underweight postmenopausal women comes as no surprise; low BMI is recognized as a major risk factor for fracture. What was surprising, though, was that only 27% of obese GLOW participants with an incident fracture were placed on bone-protective medication for secondary prevention.

In contrast, the treatment rate in nonobese women with an incident fracture was 41%, and in underweight women it was 57%. The likely explanation for the markedly lower treatment rate in the obese group is the widespread belief that obesity protects against fractures, according to Dr. Compston.

Incident fractures of the ankle and tibia were significantly more common and wrist fractures were less common in obese women, compared with nonobese study participants.

The obese subjects with an incident fracture had significantly higher rates of several comorbid conditions – asthma, emphysema, and type 1 diabetes – than did nonobese women. They also were more likely than nonobese participants with an incident fracture to have a baseline history of two or more falls within the past 2 years. They had more mobility issues as well, as reflected in their increased rate of self-reported need for arm assistance in standing up.

Obese women with an incident fracture had much higher rates of diabetes, asthma, and emphysema.

Source DR. COMPSTON