Osteoarthritis

ORLANDO — Bisphosphonate therapy was associated with a reduced prevalence of cardiovascular calcification in older women but a paradoxical increased prevalence in women under age 65 years, compared with bisphosphonate nonusers in the Multi-Ethnic Study of Atherosclerosis.

Since MESA is an observational study, this novel finding has to be considered hypothesis generating rather than definitive. It remains unclear whether the unexpectedly higher prevalence of cardiovascular (CV) calcification in younger bisphosphonate users in MESA is the result of their likely shorter duration of treatment, differential drug effects, age-related differences in the pathogenesis of calcification, indication bias related to osteoporosis, or even chance, Dr. Sammy Elmariah said at the annual scientific sessions of the American Heart Association.

Given the profound tolls that cardiovascular disease and osteoporosis take in women, replication of these new MESA findings should be sought in other large data sets, added Dr. Elmariah of Mount Sinai School of Medicine, New York.

MESA is an ongoing National Heart, Lung, and Blood Institute–funded longitudinal study of an ethnically diverse group of 6,814 men and women aged 45-84 years in six U.S. communities. All of the participants were free of CV symptoms at baseline.

Dr. Elmariah and his coworkers analyzed baseline data on bisphosphonate use and CV calcification in 3,636 participating women, 2,181 of whom were under age 65. MESA included 214 women on baseline bisphosphonate therapy. CV calcification was assessed via multidetector row helical CT or electron-beam CT.

Among women aged 65 or older, bisphosphonate use was associated with a significantly lower prevalence of CV calcification at nearly all anatomic sites assessed. For example, aortic valve calcification was 33% less common in the older bisphosphonate users than in nonusers in multivariate analyses adjusted for age, body mass index, ethnicity, socioeconomic variables, CV risk factors, statins, and hormone replacement therapy. Aortic valve ring calcification was 35% less common. Calcification of the mitral annulus was 46% less common in older users, and thoracic aorta calcification was 32% less prevalent.

The only anatomic site where calcification wasn't significantly less common in older bisphosphonate users than nonusers was in the coronary arteries, where the adjusted 10% reduction in favor of the bisphosphonate users fell short of statistical significance, Dr. Elmariah continued.

The story was very different in women under 65 years of age. Younger bisphosphonate users were an adjusted fourfold more likely to have aortic valve calcification than were bisphosphonate nonusers, 1.9-fold more likely to have aortic valve ring calcification, and 2.4-fold more likely to have calcification of the mitral annulus. They also had 2.2-fold and 1.2-fold increased rates of calcification of the thoracic aorta and coronary arteries, respectively. All of these differences achieved statistical significance.

When the women were grouped in 10-year age subsets, a gradual reduction in the adjusted prevalence of CV calcification accompanied increasing age among bisphosphonate users.

The increased prevalence of CV calcification in younger bisphosphonate users came as a surprise in light of the known pharmacologic actions of the nitrogen-containing bisphosphonates, said Dr. Elmariah. He noted that the bisphosphonates have several statin-like effects stemming from their inhibition of farnesyl pyrophosphate synthase, an enzyme downstream from HMG-CoA reductase in the mevalonate pathway.

Disclosures: Dr. Elmariah's work was funded by the New York Academy of Medicine, the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease and the NHLBI.

In an observational study, women under age 65 had more calcification (arrows).

Source ©2009 Elsevier Inc.

ORLANDO — Bisphosphonate therapy was associated with a reduced prevalence of cardiovascular calcification in older women but a paradoxical increased prevalence in women under age 65 years, compared with bisphosphonate nonusers in the Multi-Ethnic Study of Atherosclerosis.

Since MESA is an observational study, this novel finding has to be considered hypothesis generating rather than definitive. It remains unclear whether the unexpectedly higher prevalence of cardiovascular (CV) calcification in younger bisphosphonate users in MESA is the result of their likely shorter duration of treatment, differential drug effects, age-related differences in the pathogenesis of calcification, indication bias related to osteoporosis, or even chance, Dr. Sammy Elmariah said at the annual scientific sessions of the American Heart Association.

Given the profound tolls that cardiovascular disease and osteoporosis take in women, replication of these new MESA findings should be sought in other large data sets, added Dr. Elmariah of Mount Sinai School of Medicine, New York.

MESA is an ongoing National Heart, Lung, and Blood Institute–funded longitudinal study of an ethnically diverse group of 6,814 men and women aged 45-84 years in six U.S. communities. All of the participants were free of CV symptoms at baseline.

Dr. Elmariah and his coworkers analyzed baseline data on bisphosphonate use and CV calcification in 3,636 participating women, 2,181 of whom were under age 65. MESA included 214 women on baseline bisphosphonate therapy. CV calcification was assessed via multidetector row helical CT or electron-beam CT.

Among women aged 65 or older, bisphosphonate use was associated with a significantly lower prevalence of CV calcification at nearly all anatomic sites assessed. For example, aortic valve calcification was 33% less common in the older bisphosphonate users than in nonusers in multivariate analyses adjusted for age, body mass index, ethnicity, socioeconomic variables, CV risk factors, statins, and hormone replacement therapy. Aortic valve ring calcification was 35% less common. Calcification of the mitral annulus was 46% less common in older users, and thoracic aorta calcification was 32% less prevalent.

The only anatomic site where calcification wasn't significantly less common in older bisphosphonate users than nonusers was in the coronary arteries, where the adjusted 10% reduction in favor of the bisphosphonate users fell short of statistical significance, Dr. Elmariah continued.

The story was very different in women under 65 years of age. Younger bisphosphonate users were an adjusted fourfold more likely to have aortic valve calcification than were bisphosphonate nonusers, 1.9-fold more likely to have aortic valve ring calcification, and 2.4-fold more likely to have calcification of the mitral annulus. They also had 2.2-fold and 1.2-fold increased rates of calcification of the thoracic aorta and coronary arteries, respectively. All of these differences achieved statistical significance.

When the women were grouped in 10-year age subsets, a gradual reduction in the adjusted prevalence of CV calcification accompanied increasing age among bisphosphonate users.

The increased prevalence of CV calcification in younger bisphosphonate users came as a surprise in light of the known pharmacologic actions of the nitrogen-containing bisphosphonates, said Dr. Elmariah. He noted that the bisphosphonates have several statin-like effects stemming from their inhibition of farnesyl pyrophosphate synthase, an enzyme downstream from HMG-CoA reductase in the mevalonate pathway.

Disclosures: Dr. Elmariah's work was funded by the New York Academy of Medicine, the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease and the NHLBI.

In an observational study, women under age 65 had more calcification (arrows).

Source ©2009 Elsevier Inc.

ORLANDO — Bisphosphonate therapy was associated with a reduced prevalence of cardiovascular calcification in older women but a paradoxical increased prevalence in women under age 65 years, compared with bisphosphonate nonusers in the Multi-Ethnic Study of Atherosclerosis.

Since MESA is an observational study, this novel finding has to be considered hypothesis generating rather than definitive. It remains unclear whether the unexpectedly higher prevalence of cardiovascular (CV) calcification in younger bisphosphonate users in MESA is the result of their likely shorter duration of treatment, differential drug effects, age-related differences in the pathogenesis of calcification, indication bias related to osteoporosis, or even chance, Dr. Sammy Elmariah said at the annual scientific sessions of the American Heart Association.

Given the profound tolls that cardiovascular disease and osteoporosis take in women, replication of these new MESA findings should be sought in other large data sets, added Dr. Elmariah of Mount Sinai School of Medicine, New York.

MESA is an ongoing National Heart, Lung, and Blood Institute–funded longitudinal study of an ethnically diverse group of 6,814 men and women aged 45-84 years in six U.S. communities. All of the participants were free of CV symptoms at baseline.

Dr. Elmariah and his coworkers analyzed baseline data on bisphosphonate use and CV calcification in 3,636 participating women, 2,181 of whom were under age 65. MESA included 214 women on baseline bisphosphonate therapy. CV calcification was assessed via multidetector row helical CT or electron-beam CT.

Among women aged 65 or older, bisphosphonate use was associated with a significantly lower prevalence of CV calcification at nearly all anatomic sites assessed. For example, aortic valve calcification was 33% less common in the older bisphosphonate users than in nonusers in multivariate analyses adjusted for age, body mass index, ethnicity, socioeconomic variables, CV risk factors, statins, and hormone replacement therapy. Aortic valve ring calcification was 35% less common. Calcification of the mitral annulus was 46% less common in older users, and thoracic aorta calcification was 32% less prevalent.

The only anatomic site where calcification wasn't significantly less common in older bisphosphonate users than nonusers was in the coronary arteries, where the adjusted 10% reduction in favor of the bisphosphonate users fell short of statistical significance, Dr. Elmariah continued.

The story was very different in women under 65 years of age. Younger bisphosphonate users were an adjusted fourfold more likely to have aortic valve calcification than were bisphosphonate nonusers, 1.9-fold more likely to have aortic valve ring calcification, and 2.4-fold more likely to have calcification of the mitral annulus. They also had 2.2-fold and 1.2-fold increased rates of calcification of the thoracic aorta and coronary arteries, respectively. All of these differences achieved statistical significance.

When the women were grouped in 10-year age subsets, a gradual reduction in the adjusted prevalence of CV calcification accompanied increasing age among bisphosphonate users.

The increased prevalence of CV calcification in younger bisphosphonate users came as a surprise in light of the known pharmacologic actions of the nitrogen-containing bisphosphonates, said Dr. Elmariah. He noted that the bisphosphonates have several statin-like effects stemming from their inhibition of farnesyl pyrophosphate synthase, an enzyme downstream from HMG-CoA reductase in the mevalonate pathway.

Disclosures: Dr. Elmariah's work was funded by the New York Academy of Medicine, the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease and the NHLBI.

In an observational study, women under age 65 had more calcification (arrows).

Source ©2009 Elsevier Inc.

PHILADELPHIA — Vertebral fractures are present in a significant percentage of children with rheumatic diseases, and these fractures appear prior to prolonged glucocorticoid exposure, according to Dr. Leanne M. Ward.

“Vertebral fractures are an underrecognized complication of steroid-treated rheumatic disorders,” said Dr. Ward, director of the Pediatric Bone Health Clinical and Research Programs at University of Ottawa. “The question is when the fractures first occur—in the course of the disease or steroid treatment.”

Investigators from the Canadian STOPP (Steroid-Associated Osteoporosis in the Pediatric Population) Consortium evaluated the spine health of 134 children (89 girls; median age, 10 years) with rheumatic conditions.

In all, 30 children had juvenile dermatomyositis (JDM), 28 had juvenile idiopathic arthritis excluding systemic JIA, and 76 were diagnosed with other rheumatic disorders (systemic lupus erythematosus, systemic vasculitides, systemic JIA, and others).

The children underwent thoracolumbar spine x-rays and lumbar spine areal bone mineral density (LS aBMD) evaluation within 30 days of beginning glucocorticoid therapy.

A total of 7% of the group (9 of 134) had vertebral fractures. In these nine children, six patients had a single vertebral fracture and three patients had 2-5 fractures, for a total of 13 fractures. Three of the fractures (23%) were moderate and the rest were mild. Most fractures were located in the midthoracic and upper lumbar regions, said Dr. Ward at the annual meeting of the American College of Rheumatology. Although the mean LS aBMD scores for the group were lower than the norm (−0.6 plus or minus 1.22; P less than .001), LS aBMD did not predict the development of vertebral fractures. The odds for fracture were increased 10-fold if the child reported back pain.

The STOPP Consortium was founded in 2003 as a Canadian national pediatric bone health working group of investigators from 12 tertiary children's hospitals.

Dr. Ward recommends that children with rheumatic diseases undergo baseline spine radiographs at diagnosis and then annually, or more frequently if they have new-onset back pain. Children with vertebral fractures who have back pain may be candidates for bisphosphonate therapy, said Dr. Ward.

Dr. Ward reported having a business relationship with Novartis.

This image shows a fracture at L1 in a girl with JDM who takes glucocorticoids.

Source Courtesy Dr. Leanne M. Ward

PHILADELPHIA — Vertebral fractures are present in a significant percentage of children with rheumatic diseases, and these fractures appear prior to prolonged glucocorticoid exposure, according to Dr. Leanne M. Ward.

“Vertebral fractures are an underrecognized complication of steroid-treated rheumatic disorders,” said Dr. Ward, director of the Pediatric Bone Health Clinical and Research Programs at University of Ottawa. “The question is when the fractures first occur—in the course of the disease or steroid treatment.”

Investigators from the Canadian STOPP (Steroid-Associated Osteoporosis in the Pediatric Population) Consortium evaluated the spine health of 134 children (89 girls; median age, 10 years) with rheumatic conditions.

In all, 30 children had juvenile dermatomyositis (JDM), 28 had juvenile idiopathic arthritis excluding systemic JIA, and 76 were diagnosed with other rheumatic disorders (systemic lupus erythematosus, systemic vasculitides, systemic JIA, and others).

The children underwent thoracolumbar spine x-rays and lumbar spine areal bone mineral density (LS aBMD) evaluation within 30 days of beginning glucocorticoid therapy.

A total of 7% of the group (9 of 134) had vertebral fractures. In these nine children, six patients had a single vertebral fracture and three patients had 2-5 fractures, for a total of 13 fractures. Three of the fractures (23%) were moderate and the rest were mild. Most fractures were located in the midthoracic and upper lumbar regions, said Dr. Ward at the annual meeting of the American College of Rheumatology. Although the mean LS aBMD scores for the group were lower than the norm (−0.6 plus or minus 1.22; P less than .001), LS aBMD did not predict the development of vertebral fractures. The odds for fracture were increased 10-fold if the child reported back pain.

The STOPP Consortium was founded in 2003 as a Canadian national pediatric bone health working group of investigators from 12 tertiary children's hospitals.

Dr. Ward recommends that children with rheumatic diseases undergo baseline spine radiographs at diagnosis and then annually, or more frequently if they have new-onset back pain. Children with vertebral fractures who have back pain may be candidates for bisphosphonate therapy, said Dr. Ward.

Dr. Ward reported having a business relationship with Novartis.

This image shows a fracture at L1 in a girl with JDM who takes glucocorticoids.

Source Courtesy Dr. Leanne M. Ward

PHILADELPHIA — Vertebral fractures are present in a significant percentage of children with rheumatic diseases, and these fractures appear prior to prolonged glucocorticoid exposure, according to Dr. Leanne M. Ward.

“Vertebral fractures are an underrecognized complication of steroid-treated rheumatic disorders,” said Dr. Ward, director of the Pediatric Bone Health Clinical and Research Programs at University of Ottawa. “The question is when the fractures first occur—in the course of the disease or steroid treatment.”

Investigators from the Canadian STOPP (Steroid-Associated Osteoporosis in the Pediatric Population) Consortium evaluated the spine health of 134 children (89 girls; median age, 10 years) with rheumatic conditions.

In all, 30 children had juvenile dermatomyositis (JDM), 28 had juvenile idiopathic arthritis excluding systemic JIA, and 76 were diagnosed with other rheumatic disorders (systemic lupus erythematosus, systemic vasculitides, systemic JIA, and others).

The children underwent thoracolumbar spine x-rays and lumbar spine areal bone mineral density (LS aBMD) evaluation within 30 days of beginning glucocorticoid therapy.

A total of 7% of the group (9 of 134) had vertebral fractures. In these nine children, six patients had a single vertebral fracture and three patients had 2-5 fractures, for a total of 13 fractures. Three of the fractures (23%) were moderate and the rest were mild. Most fractures were located in the midthoracic and upper lumbar regions, said Dr. Ward at the annual meeting of the American College of Rheumatology. Although the mean LS aBMD scores for the group were lower than the norm (−0.6 plus or minus 1.22; P less than .001), LS aBMD did not predict the development of vertebral fractures. The odds for fracture were increased 10-fold if the child reported back pain.

The STOPP Consortium was founded in 2003 as a Canadian national pediatric bone health working group of investigators from 12 tertiary children's hospitals.

Dr. Ward recommends that children with rheumatic diseases undergo baseline spine radiographs at diagnosis and then annually, or more frequently if they have new-onset back pain. Children with vertebral fractures who have back pain may be candidates for bisphosphonate therapy, said Dr. Ward.

Dr. Ward reported having a business relationship with Novartis.

This image shows a fracture at L1 in a girl with JDM who takes glucocorticoids.

Source Courtesy Dr. Leanne M. Ward

The Food and Drug Administration wants more information on denosumab before completing its review of the monoclonal antibody for the treatment and prevention of postmenopausal osteoporosis, the manufacturer, Amgen Inc., announced.

In a “Complete Response Letter,” the FDA requested more information on the design of Amgen's planned postmarketing surveillance program, and has asked the company to conduct a new clinical program for the postmenopausal osteoporosis prevention indication, according to an Amgen statement.

The agency also has requested updated safety data and has determined that a Risk Evaluation and Mitigation Strategy (REMS) is needed for the drug, the statement said. (The FDA requires REMS for drugs with safety issues to ensure that their benefits exceed their risks.) The company plans to respond quickly to the FDA's requests pertaining to the postmenopausal osteoporosis treatment indication.

In another statement reporting the company's third-quarter earnings, Amgen announced that it also had received a separate Complete Response Letter from the FDA regarding its approval application for denosumab for the treatment and prevention of bone loss caused by hormone ablation therapy in patients with breast or prostate cancer. In that letter, the agency requested more safety information in these populations, specifically results from “additional adequate and well-controlled clinical trials” showing that denosumab does not have detrimental effects on time-to-disease progression or overall survival in patients with breast cancer who are treated with an aromatase inhibitor, and in patients with prostate cancer who receive androgen deprivation therapy, according to the company. Amgen is reviewing both letters “and will work with the FDA to determine the appropriate next steps regarding these applications,” the company indicated.

At a meeting in August, an FDA advisory committee voted that the benefits of denosumab for treating postmenopausal osteoporosis outweighed its risks, but did not support use of the drug for other indications, including osteoporosis prevention, primarily because of concerns about its long-term safety. Denosumab, a human IgG2 monoclonal antibody, targets “an essential regulator” of osteoclasts, according to Amgen. It is also being studied for other conditions associated with bone loss, including rheumatoid arthritis, and for its potential to delay bone metastases. If approved, its trade name would be Prolia.

The Food and Drug Administration wants more information on denosumab before completing its review of the monoclonal antibody for the treatment and prevention of postmenopausal osteoporosis, the manufacturer, Amgen Inc., announced.

In a “Complete Response Letter,” the FDA requested more information on the design of Amgen's planned postmarketing surveillance program, and has asked the company to conduct a new clinical program for the postmenopausal osteoporosis prevention indication, according to an Amgen statement.

The agency also has requested updated safety data and has determined that a Risk Evaluation and Mitigation Strategy (REMS) is needed for the drug, the statement said. (The FDA requires REMS for drugs with safety issues to ensure that their benefits exceed their risks.) The company plans to respond quickly to the FDA's requests pertaining to the postmenopausal osteoporosis treatment indication.

In another statement reporting the company's third-quarter earnings, Amgen announced that it also had received a separate Complete Response Letter from the FDA regarding its approval application for denosumab for the treatment and prevention of bone loss caused by hormone ablation therapy in patients with breast or prostate cancer. In that letter, the agency requested more safety information in these populations, specifically results from “additional adequate and well-controlled clinical trials” showing that denosumab does not have detrimental effects on time-to-disease progression or overall survival in patients with breast cancer who are treated with an aromatase inhibitor, and in patients with prostate cancer who receive androgen deprivation therapy, according to the company. Amgen is reviewing both letters “and will work with the FDA to determine the appropriate next steps regarding these applications,” the company indicated.

At a meeting in August, an FDA advisory committee voted that the benefits of denosumab for treating postmenopausal osteoporosis outweighed its risks, but did not support use of the drug for other indications, including osteoporosis prevention, primarily because of concerns about its long-term safety. Denosumab, a human IgG2 monoclonal antibody, targets “an essential regulator” of osteoclasts, according to Amgen. It is also being studied for other conditions associated with bone loss, including rheumatoid arthritis, and for its potential to delay bone metastases. If approved, its trade name would be Prolia.

The Food and Drug Administration wants more information on denosumab before completing its review of the monoclonal antibody for the treatment and prevention of postmenopausal osteoporosis, the manufacturer, Amgen Inc., announced.

In a “Complete Response Letter,” the FDA requested more information on the design of Amgen's planned postmarketing surveillance program, and has asked the company to conduct a new clinical program for the postmenopausal osteoporosis prevention indication, according to an Amgen statement.

The agency also has requested updated safety data and has determined that a Risk Evaluation and Mitigation Strategy (REMS) is needed for the drug, the statement said. (The FDA requires REMS for drugs with safety issues to ensure that their benefits exceed their risks.) The company plans to respond quickly to the FDA's requests pertaining to the postmenopausal osteoporosis treatment indication.

In another statement reporting the company's third-quarter earnings, Amgen announced that it also had received a separate Complete Response Letter from the FDA regarding its approval application for denosumab for the treatment and prevention of bone loss caused by hormone ablation therapy in patients with breast or prostate cancer. In that letter, the agency requested more safety information in these populations, specifically results from “additional adequate and well-controlled clinical trials” showing that denosumab does not have detrimental effects on time-to-disease progression or overall survival in patients with breast cancer who are treated with an aromatase inhibitor, and in patients with prostate cancer who receive androgen deprivation therapy, according to the company. Amgen is reviewing both letters “and will work with the FDA to determine the appropriate next steps regarding these applications,” the company indicated.

At a meeting in August, an FDA advisory committee voted that the benefits of denosumab for treating postmenopausal osteoporosis outweighed its risks, but did not support use of the drug for other indications, including osteoporosis prevention, primarily because of concerns about its long-term safety. Denosumab, a human IgG2 monoclonal antibody, targets “an essential regulator” of osteoclasts, according to Amgen. It is also being studied for other conditions associated with bone loss, including rheumatoid arthritis, and for its potential to delay bone metastases. If approved, its trade name would be Prolia.

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo). However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have FDA approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial including 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture.

The women were randomized to one of three treatment groups: zoledronic acid alone (137), zoledronic acid plus teriparatide (137), and teriparatide alone (138). The zoledronic acid dosage was 5 mg given intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Differences among treatment groups in the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 were calculated as the difference of least square means from a two-way analysis of variance model.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks.

N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively.

Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid–alone groups than in the teriparatide-alone group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

The two-drug combination increased BMD at the spine more than did teriparatide alone.

Source DR. SAAG

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo). However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have FDA approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial including 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture.

The women were randomized to one of three treatment groups: zoledronic acid alone (137), zoledronic acid plus teriparatide (137), and teriparatide alone (138). The zoledronic acid dosage was 5 mg given intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Differences among treatment groups in the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 were calculated as the difference of least square means from a two-way analysis of variance model.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks.

N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively.

Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid–alone groups than in the teriparatide-alone group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

The two-drug combination increased BMD at the spine more than did teriparatide alone.

Source DR. SAAG

PHILADELPHIA — Combining once-a-year zoledronic acid and daily teriparatide significantly increased bone mass in key skeletal sites and lowered serum levels of bone turnover biomarkers in postmenopausal women with osteoporosis, according to a study presented at the annual meeting of the American College of Rheumatology.

Previous research has not shown a bone mineral density (BMD) benefit from using the two types of drugs together. In fact, certain bisphosphonates have been shown to blunt the beneficial effects of recombinant human parathyroid hormone analogs such as teriparatide (Forteo). However, findings from animal studies suggested that zoledronic acid (Reclast) did not blunt the effect of recombinant human parathyroid hormone analogs, a finding that led the investigators to undertake the latest trial.

Both drugs have FDA approval for the management of osteoporosis in men and woman. Teriparatide also has an indication to treat corticosteroid-induced osteoporosis. Zoledronic acid has an additional indication for use in the treatment of osteoporosis in patients who have osteoporosis and have already had a fracture.

The trial including 412 postmenopausal women considered to be at high risk for fracture. They were diagnosed with osteoporosis on the strength of having a T score that was 2.5 standard deviations below peak bone mass, or having a slightly better T score but a history of at least one fracture.

The women were randomized to one of three treatment groups: zoledronic acid alone (137), zoledronic acid plus teriparatide (137), and teriparatide alone (138). The zoledronic acid dosage was 5 mg given intravenously once per year. Teriparatide was given daily in a subcutaneous dose of 20 mcg.

Use of the two drugs in combination increased BMD at the spine more than did teriparatide alone, and at the hip more than did zoledronic acid alone, according to study presenter Dr. Kenneth G. Saag, the Jane Knight Lowe Chair of Medicine in Rheumatology at the University of Alabama at Birmingham.

BMD at the spine increased 7.51%, 7.05%, and 4.37% in the combination arm, teriparatide arm, and zoledronic acid arm, respectively. Combination therapy significantly increased lumbar spine BMD at week 13 and 26 and total hip BMD at weeks 13, 26, and 52, compared with teriparatide alone.

Differences among treatment groups in the percent change in lumbar spine and total hip BMD at weeks 13, 26, and 52 were calculated as the difference of least square means from a two-way analysis of variance model.

In terms of serum markers of bone turnover, C-telopeptide declined within 4 weeks and rose progressively thereafter in the combination arm, with levels above baseline within 39 weeks.

N-propeptide of type 1 collagen increased for up to 4 weeks, declined to a nadir at week 8, and then rose progressively with levels above baseline by week 26. Levels of both markers were lower with combination therapy than with teriparatide alone throughout the trial.

The incidence of serious adverse events was 9.5%, 14.6%, and 10.9% in the combination, zoledronic acid, and teriparatide arms, respectively.

Transient postinfusion flulike symptoms were more common in the combination and zoledronic acid–alone groups than in the teriparatide-alone group.

Dr. Saag disclosed financial relationships with Eli Lilly & Co., Merck & Co., Novartis, Amgen Inc., Roche, Procter & Gamble Co., NPS Pharmaceuticals Inc., Pfizer Inc., Sanofi-Aventis, TAP Pharmaceutical Products Inc., and GlaxoSmithKline.

The two-drug combination increased BMD at the spine more than did teriparatide alone.

Source DR. SAAG

DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.

“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”

Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra.

“This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids. “A number of studies have shown that patients on glucocorticoids, for the most part, tend to fracture at bone densities that are greater than [those of] postmenopausal women with osteoporosis.”

Dr. Lane and her colleagues have followed bone density in mice that were exposed to moderate doses of glucocorticoids. They found that most of the bone loss occurred very quickly. At roughly a month (28 days), there was a 20% loss in trabecular vertebral bone mineral density (BMD) as measured by quantitative CT, a 3-D means of assessing bone volume. However, during days 28–56 there was little additional loss of bone mass. “Upon giving the mice glucocorticoids, we found that bone resorption went up very quickly,” said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis. By day 7, there was nearly a doubling in bone turnover as measured by CTx, a C-terminal telopeptide of type I collagen, which is a serum marker of bone resorption.

In addition, they found very little change in serum levels of osteocalcin (a biomarker of bone formation) for the first 7 days. Osteocalcin levels then began to decline. “It looks like glucocorticoids also change osteocyte gene expression,” she said.

Thus, with glucocorticoids, bone formation goes down and bone resorption goes up. “I always say that bone doesn't have a chance in the presence of glucocorticoids,” said Dr. Lane.

Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”

Patient No. 1

A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.

As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.

This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.

So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).

“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995–1000).

Bisphosphonates do appear to improve bone density in these patients. In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292–9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment. It's also important to think about trying to minimize the dose of prednisone.

The woman returned for x-ray of the spine 2 years later. Her bone density was stable, although she had developed mild esophageal symptoms. On endoscopy, these were attributed to esophagitis. She was still taking low-dose prednisone, so she was switched to a different bisphosphonate.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25–50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on the fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

“The reports that have been published so far have generally not identified any developmental or bone density abnormalities,” in association with prenatal exposure to bisphosphonates, Dr. Sambrook noted. Some reports have identified lower birth weight, lower gestational age at birth, and higher rates of spontaneous abortion with exposure to bisphosphonates.

“These have to be interpreted in context. These women are already ill—otherwise they wouldn't be on steroids—and that's going to affect those types of outcomes,” he cautioned.

In animal studies, in which pregnant animals have been subjected to 10 times the recommended human bisphosphonate dose, maternal toxicity, growth retardation, and fetal loss have been reported. “But these are very high doses. What do we see in real life?” Dr. Sambrook asked.

In a study from Canada published this year, researchers followed 21 women who were exposed to bisphosphonates either during or less than 3 months before pregnancy, and then compared them with matched control women. Outcomes were similar between the two groups, suggesting that preconceptional and first-trimester use of bisphosphonates may not pose substantial fetal risks (Bone 2009;44:428–30).

“These data are fairly reassuring in terms of the safety in patients treated prior to becoming pregnant or … if they become pregnant while on bisphosphonates,” he said. However, bisphosphonates should be stopped as soon as it's known that a patient is pregnant, if not prior to her becoming pregnant.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported significant financial relationships with several pharmaceutical companies.

Dual-energy x-ray absorptiometry provides “areal” BMD (g/cm

Source ©Elsevier

DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.

“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”

Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra.

“This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids. “A number of studies have shown that patients on glucocorticoids, for the most part, tend to fracture at bone densities that are greater than [those of] postmenopausal women with osteoporosis.”

Dr. Lane and her colleagues have followed bone density in mice that were exposed to moderate doses of glucocorticoids. They found that most of the bone loss occurred very quickly. At roughly a month (28 days), there was a 20% loss in trabecular vertebral bone mineral density (BMD) as measured by quantitative CT, a 3-D means of assessing bone volume. However, during days 28–56 there was little additional loss of bone mass. “Upon giving the mice glucocorticoids, we found that bone resorption went up very quickly,” said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis. By day 7, there was nearly a doubling in bone turnover as measured by CTx, a C-terminal telopeptide of type I collagen, which is a serum marker of bone resorption.

In addition, they found very little change in serum levels of osteocalcin (a biomarker of bone formation) for the first 7 days. Osteocalcin levels then began to decline. “It looks like glucocorticoids also change osteocyte gene expression,” she said.

Thus, with glucocorticoids, bone formation goes down and bone resorption goes up. “I always say that bone doesn't have a chance in the presence of glucocorticoids,” said Dr. Lane.

Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”

Patient No. 1

A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.

As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.

This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.

So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).

“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995–1000).

Bisphosphonates do appear to improve bone density in these patients. In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292–9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment. It's also important to think about trying to minimize the dose of prednisone.

The woman returned for x-ray of the spine 2 years later. Her bone density was stable, although she had developed mild esophageal symptoms. On endoscopy, these were attributed to esophagitis. She was still taking low-dose prednisone, so she was switched to a different bisphosphonate.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25–50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on the fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

“The reports that have been published so far have generally not identified any developmental or bone density abnormalities,” in association with prenatal exposure to bisphosphonates, Dr. Sambrook noted. Some reports have identified lower birth weight, lower gestational age at birth, and higher rates of spontaneous abortion with exposure to bisphosphonates.

“These have to be interpreted in context. These women are already ill—otherwise they wouldn't be on steroids—and that's going to affect those types of outcomes,” he cautioned.

In animal studies, in which pregnant animals have been subjected to 10 times the recommended human bisphosphonate dose, maternal toxicity, growth retardation, and fetal loss have been reported. “But these are very high doses. What do we see in real life?” Dr. Sambrook asked.

In a study from Canada published this year, researchers followed 21 women who were exposed to bisphosphonates either during or less than 3 months before pregnancy, and then compared them with matched control women. Outcomes were similar between the two groups, suggesting that preconceptional and first-trimester use of bisphosphonates may not pose substantial fetal risks (Bone 2009;44:428–30).

“These data are fairly reassuring in terms of the safety in patients treated prior to becoming pregnant or … if they become pregnant while on bisphosphonates,” he said. However, bisphosphonates should be stopped as soon as it's known that a patient is pregnant, if not prior to her becoming pregnant.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported significant financial relationships with several pharmaceutical companies.

Dual-energy x-ray absorptiometry provides “areal” BMD (g/cm

Source ©Elsevier

DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.

“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”

Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra.

“This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids. “A number of studies have shown that patients on glucocorticoids, for the most part, tend to fracture at bone densities that are greater than [those of] postmenopausal women with osteoporosis.”

Dr. Lane and her colleagues have followed bone density in mice that were exposed to moderate doses of glucocorticoids. They found that most of the bone loss occurred very quickly. At roughly a month (28 days), there was a 20% loss in trabecular vertebral bone mineral density (BMD) as measured by quantitative CT, a 3-D means of assessing bone volume. However, during days 28–56 there was little additional loss of bone mass. “Upon giving the mice glucocorticoids, we found that bone resorption went up very quickly,” said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis. By day 7, there was nearly a doubling in bone turnover as measured by CTx, a C-terminal telopeptide of type I collagen, which is a serum marker of bone resorption.

In addition, they found very little change in serum levels of osteocalcin (a biomarker of bone formation) for the first 7 days. Osteocalcin levels then began to decline. “It looks like glucocorticoids also change osteocyte gene expression,” she said.

Thus, with glucocorticoids, bone formation goes down and bone resorption goes up. “I always say that bone doesn't have a chance in the presence of glucocorticoids,” said Dr. Lane.

Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”

Patient No. 1

A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.

As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.

This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.

So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).

“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995–1000).

Bisphosphonates do appear to improve bone density in these patients. In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292–9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment. It's also important to think about trying to minimize the dose of prednisone.

The woman returned for x-ray of the spine 2 years later. Her bone density was stable, although she had developed mild esophageal symptoms. On endoscopy, these were attributed to esophagitis. She was still taking low-dose prednisone, so she was switched to a different bisphosphonate.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25–50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on the fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

“The reports that have been published so far have generally not identified any developmental or bone density abnormalities,” in association with prenatal exposure to bisphosphonates, Dr. Sambrook noted. Some reports have identified lower birth weight, lower gestational age at birth, and higher rates of spontaneous abortion with exposure to bisphosphonates.

“These have to be interpreted in context. These women are already ill—otherwise they wouldn't be on steroids—and that's going to affect those types of outcomes,” he cautioned.

In animal studies, in which pregnant animals have been subjected to 10 times the recommended human bisphosphonate dose, maternal toxicity, growth retardation, and fetal loss have been reported. “But these are very high doses. What do we see in real life?” Dr. Sambrook asked.

In a study from Canada published this year, researchers followed 21 women who were exposed to bisphosphonates either during or less than 3 months before pregnancy, and then compared them with matched control women. Outcomes were similar between the two groups, suggesting that preconceptional and first-trimester use of bisphosphonates may not pose substantial fetal risks (Bone 2009;44:428–30).

“These data are fairly reassuring in terms of the safety in patients treated prior to becoming pregnant or … if they become pregnant while on bisphosphonates,” he said. However, bisphosphonates should be stopped as soon as it's known that a patient is pregnant, if not prior to her becoming pregnant.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported significant financial relationships with several pharmaceutical companies.

Dual-energy x-ray absorptiometry provides “areal” BMD (g/cm

Source ©Elsevier

Results of two separate pivotal trials of the investigational drug denosumab show significant decreases in the risk of fractures during 36 months of twice-yearly injections in 7,868 postmenopausal women with osteoporosis and in 1,468 men receiving androgen deprivation therapy for prostate cancer, compared with placebo injections.

The two randomized, double-blind, multicenter trials were published in the New England Journal of Medicine (2009 [doi:10.1056/NEJM0a0809493doi;10.1056/NEJM0a0809003

The FDA's Reproductive Health Drugs Advisory Committee has recommended approval of the drug for treating osteoporosis in postmenopausal women but not for preventing it. (See story, p. 8.)

The benefits of denosumab therapy have the potential to extend beyond osteoporosis to the management of rheumatoid arthritis.

Rheumatologist Robin Dore noted in an interview with Rheumatology News that patients with rheumatoid arthritis are at increased risk of fracture even if they have never received glucocorticoid therapy due to the chronic inflammatory state seen in these patients. If a phase III trial in RA patients “confirms the findings of our smaller phase II study [Arthritis Rheum 2008;58;1299-309], in my opinion denosumab could be used as a therapy to treat both the [RA] and low bone mass seen in this population of patients,” she said.

“Our phase II study was too small to evaluate the efficacy of denosumab to reduce fractures in patients [with RA] but it was found to increase bone mineral density in patients [with RA] both with and without glucocorticoid treatment and with and without bisphosphonate treatment.”

Although a phase III study in RA patients (if performed) would be larger, “it still would not have the power to demonstrate fracture reduction in this population,” said Dr. Dore of the University of California, Los Angeles.

In osteoporotic postmenopausal women aged 60-90 years with a baseline bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip, the cumulative incidence of new vertebral fractures was 2.3% on denosumab and 7.2% on placebo, a relative decrease of 68%.

Reduction in new vertebral fracture was the primary end point of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial. The primary outcomes of HALT (Hormone Ablation Bone Loss Trial) showed significantly improved lumbar density at 24 months in the denosumab group (an increase of 5.6%), compared with the placebo group, (which had a bone density loss of 1%,) in men receiving androgen deprivation therapy for prostate cancer. The age range of the denosumab group was 48-92 years and the age range of the placebo group was 50-97 years. The original 2-year study protocol was extended to 3 years for further evaluation. One of the secondary end points showed significantly decreased risk for new vertebral fractures at 36 months on denosumab (1.5%), compared with placebo (3.9%), a relative improvement of 62%.

Amgen, the company that is developing the drug for the United States, has applied for FDA approval for denosumab (to be marketed as Prolia) to treat postmenopausal osteoporosis and to prevent bone loss in patients undergoing hormone ablation for prostate or breast cancer. A previous study found that denosumab was associated with increased bone mineral density in women receiving aromatase-inhibitor therapy for breast cancer (J. Clin. Oncol. 2008;26:4875-82).

Dr. Steven R. Cummings of the University of California, San Francisco, and his associates in the FREEDOM trial noted that rare adverse effects associated with other osteoporosis therapies—necrosis of the jaw and fractures of the femoral shaft—were not seen with denosumab. However, theoretical concerns have been raised previously about a possible increase in the risk of cancer or infection with denosumab because of the drug's potential effects on the immune system.

Dr. Cummings reported no significant increase in the rate of serious infections, but did find significant increases in risks for eczema (3% vs. 1.7% on placebo), cellulitis (0.3% vs. less than 0.1%), and flatulence (2.2% vs. 1.4%).

Dr. Matthew R. Smith of Massachusetts General Hospital, Boston, and his associates in HALT reported that rates of adverse events were similar between groups. However, rates were higher in the denosumab group, compared with placebo, for serious adverse events (34.6% vs. 30.6%), serious adverse events related to infection (5.9% vs. 4.6%), and cataracts (4.7% vs. 1.2%), although none of the cataracts was considered to be related to the drug treatment.

In an accompanying editorial, Dr. Sundeep Khosla of the Mayo Clinic, Rochester, Minn., noted that a previous study of 314 women with low bone mineral density found that neoplasms developed in six patients randomized to denosumab therapy and in none on placebo, and serious infections developed in three patients on the drug and none on placebo (N. Engl. J. Med. 2006;354:821-31). “Although not statistically significant, such findings support ongoing surveillance of patients receiving denosumab,” Dr. Khosla suggested (N. Engl. J. Med. 2009 [doi:10.1056NEJMe0905480]).

The studies were funded by Amgen. Dr. Cummings has received fees and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Organon, Pfizer, and Novartis. Dr. Smith has received fees from Amgen, Novartis, and GTx. Their study associates work for, are invested in, and/or receive support from Amgen and other companies. Dr. Khosla reported having no potential conflicts of interest related to these topics. Dr. Dore reported receiving funding from Amgen for clinical trials, is a consultant to Amgen, and participates on their speakers bureau.

Denosumab use was not associated with jaw osteonecrosis or femoral shaft fractures seen with other agents.

Source DR. CUMMINGS

Results of two separate pivotal trials of the investigational drug denosumab show significant decreases in the risk of fractures during 36 months of twice-yearly injections in 7,868 postmenopausal women with osteoporosis and in 1,468 men receiving androgen deprivation therapy for prostate cancer, compared with placebo injections.

The two randomized, double-blind, multicenter trials were published in the New England Journal of Medicine (2009 [doi:10.1056/NEJM0a0809493doi;10.1056/NEJM0a0809003

The FDA's Reproductive Health Drugs Advisory Committee has recommended approval of the drug for treating osteoporosis in postmenopausal women but not for preventing it. (See story, p. 8.)

The benefits of denosumab therapy have the potential to extend beyond osteoporosis to the management of rheumatoid arthritis.

Rheumatologist Robin Dore noted in an interview with Rheumatology News that patients with rheumatoid arthritis are at increased risk of fracture even if they have never received glucocorticoid therapy due to the chronic inflammatory state seen in these patients. If a phase III trial in RA patients “confirms the findings of our smaller phase II study [Arthritis Rheum 2008;58;1299-309], in my opinion denosumab could be used as a therapy to treat both the [RA] and low bone mass seen in this population of patients,” she said.

“Our phase II study was too small to evaluate the efficacy of denosumab to reduce fractures in patients [with RA] but it was found to increase bone mineral density in patients [with RA] both with and without glucocorticoid treatment and with and without bisphosphonate treatment.”

Although a phase III study in RA patients (if performed) would be larger, “it still would not have the power to demonstrate fracture reduction in this population,” said Dr. Dore of the University of California, Los Angeles.

In osteoporotic postmenopausal women aged 60-90 years with a baseline bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip, the cumulative incidence of new vertebral fractures was 2.3% on denosumab and 7.2% on placebo, a relative decrease of 68%.

Reduction in new vertebral fracture was the primary end point of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial. The primary outcomes of HALT (Hormone Ablation Bone Loss Trial) showed significantly improved lumbar density at 24 months in the denosumab group (an increase of 5.6%), compared with the placebo group, (which had a bone density loss of 1%,) in men receiving androgen deprivation therapy for prostate cancer. The age range of the denosumab group was 48-92 years and the age range of the placebo group was 50-97 years. The original 2-year study protocol was extended to 3 years for further evaluation. One of the secondary end points showed significantly decreased risk for new vertebral fractures at 36 months on denosumab (1.5%), compared with placebo (3.9%), a relative improvement of 62%.

Amgen, the company that is developing the drug for the United States, has applied for FDA approval for denosumab (to be marketed as Prolia) to treat postmenopausal osteoporosis and to prevent bone loss in patients undergoing hormone ablation for prostate or breast cancer. A previous study found that denosumab was associated with increased bone mineral density in women receiving aromatase-inhibitor therapy for breast cancer (J. Clin. Oncol. 2008;26:4875-82).

Dr. Steven R. Cummings of the University of California, San Francisco, and his associates in the FREEDOM trial noted that rare adverse effects associated with other osteoporosis therapies—necrosis of the jaw and fractures of the femoral shaft—were not seen with denosumab. However, theoretical concerns have been raised previously about a possible increase in the risk of cancer or infection with denosumab because of the drug's potential effects on the immune system.

Dr. Cummings reported no significant increase in the rate of serious infections, but did find significant increases in risks for eczema (3% vs. 1.7% on placebo), cellulitis (0.3% vs. less than 0.1%), and flatulence (2.2% vs. 1.4%).

Dr. Matthew R. Smith of Massachusetts General Hospital, Boston, and his associates in HALT reported that rates of adverse events were similar between groups. However, rates were higher in the denosumab group, compared with placebo, for serious adverse events (34.6% vs. 30.6%), serious adverse events related to infection (5.9% vs. 4.6%), and cataracts (4.7% vs. 1.2%), although none of the cataracts was considered to be related to the drug treatment.

In an accompanying editorial, Dr. Sundeep Khosla of the Mayo Clinic, Rochester, Minn., noted that a previous study of 314 women with low bone mineral density found that neoplasms developed in six patients randomized to denosumab therapy and in none on placebo, and serious infections developed in three patients on the drug and none on placebo (N. Engl. J. Med. 2006;354:821-31). “Although not statistically significant, such findings support ongoing surveillance of patients receiving denosumab,” Dr. Khosla suggested (N. Engl. J. Med. 2009 [doi:10.1056NEJMe0905480]).

The studies were funded by Amgen. Dr. Cummings has received fees and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Organon, Pfizer, and Novartis. Dr. Smith has received fees from Amgen, Novartis, and GTx. Their study associates work for, are invested in, and/or receive support from Amgen and other companies. Dr. Khosla reported having no potential conflicts of interest related to these topics. Dr. Dore reported receiving funding from Amgen for clinical trials, is a consultant to Amgen, and participates on their speakers bureau.

Denosumab use was not associated with jaw osteonecrosis or femoral shaft fractures seen with other agents.

Source DR. CUMMINGS

Results of two separate pivotal trials of the investigational drug denosumab show significant decreases in the risk of fractures during 36 months of twice-yearly injections in 7,868 postmenopausal women with osteoporosis and in 1,468 men receiving androgen deprivation therapy for prostate cancer, compared with placebo injections.

The two randomized, double-blind, multicenter trials were published in the New England Journal of Medicine (2009 [doi:10.1056/NEJM0a0809493doi;10.1056/NEJM0a0809003

The FDA's Reproductive Health Drugs Advisory Committee has recommended approval of the drug for treating osteoporosis in postmenopausal women but not for preventing it. (See story, p. 8.)

The benefits of denosumab therapy have the potential to extend beyond osteoporosis to the management of rheumatoid arthritis.

Rheumatologist Robin Dore noted in an interview with Rheumatology News that patients with rheumatoid arthritis are at increased risk of fracture even if they have never received glucocorticoid therapy due to the chronic inflammatory state seen in these patients. If a phase III trial in RA patients “confirms the findings of our smaller phase II study [Arthritis Rheum 2008;58;1299-309], in my opinion denosumab could be used as a therapy to treat both the [RA] and low bone mass seen in this population of patients,” she said.

“Our phase II study was too small to evaluate the efficacy of denosumab to reduce fractures in patients [with RA] but it was found to increase bone mineral density in patients [with RA] both with and without glucocorticoid treatment and with and without bisphosphonate treatment.”

Although a phase III study in RA patients (if performed) would be larger, “it still would not have the power to demonstrate fracture reduction in this population,” said Dr. Dore of the University of California, Los Angeles.

In osteoporotic postmenopausal women aged 60-90 years with a baseline bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip, the cumulative incidence of new vertebral fractures was 2.3% on denosumab and 7.2% on placebo, a relative decrease of 68%.

Reduction in new vertebral fracture was the primary end point of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial. The primary outcomes of HALT (Hormone Ablation Bone Loss Trial) showed significantly improved lumbar density at 24 months in the denosumab group (an increase of 5.6%), compared with the placebo group, (which had a bone density loss of 1%,) in men receiving androgen deprivation therapy for prostate cancer. The age range of the denosumab group was 48-92 years and the age range of the placebo group was 50-97 years. The original 2-year study protocol was extended to 3 years for further evaluation. One of the secondary end points showed significantly decreased risk for new vertebral fractures at 36 months on denosumab (1.5%), compared with placebo (3.9%), a relative improvement of 62%.

Amgen, the company that is developing the drug for the United States, has applied for FDA approval for denosumab (to be marketed as Prolia) to treat postmenopausal osteoporosis and to prevent bone loss in patients undergoing hormone ablation for prostate or breast cancer. A previous study found that denosumab was associated with increased bone mineral density in women receiving aromatase-inhibitor therapy for breast cancer (J. Clin. Oncol. 2008;26:4875-82).

Dr. Steven R. Cummings of the University of California, San Francisco, and his associates in the FREEDOM trial noted that rare adverse effects associated with other osteoporosis therapies—necrosis of the jaw and fractures of the femoral shaft—were not seen with denosumab. However, theoretical concerns have been raised previously about a possible increase in the risk of cancer or infection with denosumab because of the drug's potential effects on the immune system.

Dr. Cummings reported no significant increase in the rate of serious infections, but did find significant increases in risks for eczema (3% vs. 1.7% on placebo), cellulitis (0.3% vs. less than 0.1%), and flatulence (2.2% vs. 1.4%).

Dr. Matthew R. Smith of Massachusetts General Hospital, Boston, and his associates in HALT reported that rates of adverse events were similar between groups. However, rates were higher in the denosumab group, compared with placebo, for serious adverse events (34.6% vs. 30.6%), serious adverse events related to infection (5.9% vs. 4.6%), and cataracts (4.7% vs. 1.2%), although none of the cataracts was considered to be related to the drug treatment.

In an accompanying editorial, Dr. Sundeep Khosla of the Mayo Clinic, Rochester, Minn., noted that a previous study of 314 women with low bone mineral density found that neoplasms developed in six patients randomized to denosumab therapy and in none on placebo, and serious infections developed in three patients on the drug and none on placebo (N. Engl. J. Med. 2006;354:821-31). “Although not statistically significant, such findings support ongoing surveillance of patients receiving denosumab,” Dr. Khosla suggested (N. Engl. J. Med. 2009 [doi:10.1056NEJMe0905480]).

The studies were funded by Amgen. Dr. Cummings has received fees and/or grant support from Amgen, Eli Lilly, GlaxoSmithKline, Organon, Pfizer, and Novartis. Dr. Smith has received fees from Amgen, Novartis, and GTx. Their study associates work for, are invested in, and/or receive support from Amgen and other companies. Dr. Khosla reported having no potential conflicts of interest related to these topics. Dr. Dore reported receiving funding from Amgen for clinical trials, is a consultant to Amgen, and participates on their speakers bureau.

Denosumab use was not associated with jaw osteonecrosis or femoral shaft fractures seen with other agents.

Source DR. CUMMINGS

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation.

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.” Those discussions should include information about how to mitigate risk factors.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation.

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.” Those discussions should include information about how to mitigate risk factors.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation.

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.” Those discussions should include information about how to mitigate risk factors.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

Benign positional vertigo appears to strongly correlate with osteopenia and osteoporosis in both men and women, researchers in a case-control study have concluded.

Compared to controls, patients with osteopenia were twice as likely to experience positional vertigo, and those with osteoporosis were three times as likely to experience the disorder, Dr. Ji Sook Kim and colleagues wrote.

“These findings suggest a deranged calcium metabolism in idiopathic benign positional vertigo,” Dr. Kim of the Seoul National University College of Medicine, Korea, said in an interview. “Restoring normal calcium metabolism may prevent recurrences” of BPV.

The study compared bone mineral density in 209 patients with a diagnosis of idiopathic benign positional vertigo (BPV) and 202 controls. Most of the patients (142) were female; their mean age was 60 years.

Among female patients, only 28% had normal bone mineral density, while 47% had osteopenia (T score greater than −2.5 and less than −1.0) and 25% had osteoporosis (T score = −2.5). Among female controls, normal bone mass was found in 57%; 33% had osteopenia and 9% had osteoporosis. (Percentages do not add up to 100% due to rounding.) The differences were significant at all points measured (Neurology 2009;72:1069-76).

In male patients, 48% had normal bone mass, while 40% had osteopenia and 12% had osteoporosis. Among male controls, 67% had normal bone mass, 27% had osteopenia, and 6% had osteoporosis. The differences were significant at the femur and first lumbar vertebra, but not at the other lumbar measurements.

Recurrent attacks of BPV (defined as at least two previous attacks at least 1 month apart) had occurred in 40% of patients. Compared to patients with new-onset BPV, patients with recurrent BPV were older (62 vs. 60 years) and more likely to be women (77% vs. 62%). A logistic regression analysis controlled for age, sex, smoking, and hyperphosphatemia; none of these variables represented a significant risk factor for BPV.

In women older than 45 years, the mean lowest T scores were lower in the recurrent group than in the new-onset group (−2.1 vs. −1.6). There were no between-group T-score differences in younger patients. This finding supports the premise that estrogen deficiency may contribute to the development of BPV by weakening the bond of otoconia to the utricle, the investigators wrote. In men, the weakening may be the result of bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

Benign positional vertigo appears to strongly correlate with osteopenia and osteoporosis in both men and women, researchers in a case-control study have concluded.

Compared to controls, patients with osteopenia were twice as likely to experience positional vertigo, and those with osteoporosis were three times as likely to experience the disorder, Dr. Ji Sook Kim and colleagues wrote.

“These findings suggest a deranged calcium metabolism in idiopathic benign positional vertigo,” Dr. Kim of the Seoul National University College of Medicine, Korea, said in an interview. “Restoring normal calcium metabolism may prevent recurrences” of BPV.

The study compared bone mineral density in 209 patients with a diagnosis of idiopathic benign positional vertigo (BPV) and 202 controls. Most of the patients (142) were female; their mean age was 60 years.

Among female patients, only 28% had normal bone mineral density, while 47% had osteopenia (T score greater than −2.5 and less than −1.0) and 25% had osteoporosis (T score = −2.5). Among female controls, normal bone mass was found in 57%; 33% had osteopenia and 9% had osteoporosis. (Percentages do not add up to 100% due to rounding.) The differences were significant at all points measured (Neurology 2009;72:1069-76).

In male patients, 48% had normal bone mass, while 40% had osteopenia and 12% had osteoporosis. Among male controls, 67% had normal bone mass, 27% had osteopenia, and 6% had osteoporosis. The differences were significant at the femur and first lumbar vertebra, but not at the other lumbar measurements.

Recurrent attacks of BPV (defined as at least two previous attacks at least 1 month apart) had occurred in 40% of patients. Compared to patients with new-onset BPV, patients with recurrent BPV were older (62 vs. 60 years) and more likely to be women (77% vs. 62%). A logistic regression analysis controlled for age, sex, smoking, and hyperphosphatemia; none of these variables represented a significant risk factor for BPV.

In women older than 45 years, the mean lowest T scores were lower in the recurrent group than in the new-onset group (−2.1 vs. −1.6). There were no between-group T-score differences in younger patients. This finding supports the premise that estrogen deficiency may contribute to the development of BPV by weakening the bond of otoconia to the utricle, the investigators wrote. In men, the weakening may be the result of bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

Benign positional vertigo appears to strongly correlate with osteopenia and osteoporosis in both men and women, researchers in a case-control study have concluded.

Compared to controls, patients with osteopenia were twice as likely to experience positional vertigo, and those with osteoporosis were three times as likely to experience the disorder, Dr. Ji Sook Kim and colleagues wrote.

“These findings suggest a deranged calcium metabolism in idiopathic benign positional vertigo,” Dr. Kim of the Seoul National University College of Medicine, Korea, said in an interview. “Restoring normal calcium metabolism may prevent recurrences” of BPV.

The study compared bone mineral density in 209 patients with a diagnosis of idiopathic benign positional vertigo (BPV) and 202 controls. Most of the patients (142) were female; their mean age was 60 years.

Among female patients, only 28% had normal bone mineral density, while 47% had osteopenia (T score greater than −2.5 and less than −1.0) and 25% had osteoporosis (T score = −2.5). Among female controls, normal bone mass was found in 57%; 33% had osteopenia and 9% had osteoporosis. (Percentages do not add up to 100% due to rounding.) The differences were significant at all points measured (Neurology 2009;72:1069-76).

In male patients, 48% had normal bone mass, while 40% had osteopenia and 12% had osteoporosis. Among male controls, 67% had normal bone mass, 27% had osteopenia, and 6% had osteoporosis. The differences were significant at the femur and first lumbar vertebra, but not at the other lumbar measurements.

Recurrent attacks of BPV (defined as at least two previous attacks at least 1 month apart) had occurred in 40% of patients. Compared to patients with new-onset BPV, patients with recurrent BPV were older (62 vs. 60 years) and more likely to be women (77% vs. 62%). A logistic regression analysis controlled for age, sex, smoking, and hyperphosphatemia; none of these variables represented a significant risk factor for BPV.

In women older than 45 years, the mean lowest T scores were lower in the recurrent group than in the new-onset group (−2.1 vs. −1.6). There were no between-group T-score differences in younger patients. This finding supports the premise that estrogen deficiency may contribute to the development of BPV by weakening the bond of otoconia to the utricle, the investigators wrote. In men, the weakening may be the result of bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

CHICAGO — Fracture risk increases in arthritis patients within about 3 months of starting corticosteroids and remains high, according to Dr. Nelson Watts.

“How much of this is steroids and how much of this is the underlying disease is unanswered,” said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati.

Glucocorticoid-induced osteoporosis results from a variety of systemic effects of corticosteroids, but it's the combination of reduced bone formation and increased bone resorption that causes a “double whammy” for patients—a troubling aspect for rheumatologists, who regularly dispense corticosteroids for their patients, Dr. Watts said at a symposium sponsored by the American College of Rheumatology.

The exact dose at which corticosteroids increase fracture risk is also difficult to tease out because of the underlying disease. One study observed that fracture risk was dose dependent and significantly higher with 2.5 mg/day or more of oral prednisone, with increases of 61% in hip and 160% in vertebral fractures (J. Bone Miner. Res. 2000;15:993-1000).

“It may well be that people who need 2.5 [mg]/day of prednisone are at increased risk for fracture not because of prednisone, but because of their rheumatoid arthritis; … clearly, as the dose goes up, the risk increases,” he said.

The American College of Rheumatology just began the process of revising its 2001 guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis. The current guidelines highlight lifestyle modifications, such as calcium and vitamin D supplementation, weight-bearing exercise, and minimization of alcohol intake.

There is at least one supportive trial for virtually all therapies, but several intervention trials have produced conflicting results for some agents, according to a recent review of glucocorticoids and the risk of osteoporosis (Expert Opin. Drug Saf. 2009;8:33-47).

The value of calcium and vitamin D supplementation is unclear, Dr. Watts said. In a relatively small trial in 96 RA patients on prednisone, daily supplementation with 500 IU of vitamin D and 1,000 mg of calcium carbonate per day significantly improved bone mineral density, at a rate of 0.72% in the lumbar spine and 0.85% in the trochanter per year, compared with losses of 2% and 0.9%, respectively, among patients on placebo (Ann. Intern. Med. 1996;125:961-8).

In four prospective studies in 173 patients who recently started corticosteroid therapy, however, bone loss occurred at a rate of 3%-5% per year, despite daily supplementation with 500-800 mg of calcium.

Two other studies that Dr. Watts highlighted reported no bone loss in patients who were given up to 1,000 mg per day of calcium and up to 500 IU per day of vitamin D, although he noted that these patients had been on corticosteroid therapy for at least 1 year and in most cases almost 5 years.

“It's not clear to me how much of a role vitamin D and calcium will play in preventing bone loss,” he said.

Studies show that the risk for spinal fracture falls within a year or two of stopping therapy, although hip fracture risk remains increased over baseline.

Dr. Watts disclosed that he has relationships with Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., Sanofi-Aventis, Novo Nordisk Inc., and Novartis Pharmaceuticals Corp., which manufactures Reclast.

CHICAGO — Fracture risk increases in arthritis patients within about 3 months of starting corticosteroids and remains high, according to Dr. Nelson Watts.

“How much of this is steroids and how much of this is the underlying disease is unanswered,” said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati.

Glucocorticoid-induced osteoporosis results from a variety of systemic effects of corticosteroids, but it's the combination of reduced bone formation and increased bone resorption that causes a “double whammy” for patients—a troubling aspect for rheumatologists, who regularly dispense corticosteroids for their patients, Dr. Watts said at a symposium sponsored by the American College of Rheumatology.

The exact dose at which corticosteroids increase fracture risk is also difficult to tease out because of the underlying disease. One study observed that fracture risk was dose dependent and significantly higher with 2.5 mg/day or more of oral prednisone, with increases of 61% in hip and 160% in vertebral fractures (J. Bone Miner. Res. 2000;15:993-1000).

“It may well be that people who need 2.5 [mg]/day of prednisone are at increased risk for fracture not because of prednisone, but because of their rheumatoid arthritis; … clearly, as the dose goes up, the risk increases,” he said.

The American College of Rheumatology just began the process of revising its 2001 guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis. The current guidelines highlight lifestyle modifications, such as calcium and vitamin D supplementation, weight-bearing exercise, and minimization of alcohol intake.

There is at least one supportive trial for virtually all therapies, but several intervention trials have produced conflicting results for some agents, according to a recent review of glucocorticoids and the risk of osteoporosis (Expert Opin. Drug Saf. 2009;8:33-47).

The value of calcium and vitamin D supplementation is unclear, Dr. Watts said. In a relatively small trial in 96 RA patients on prednisone, daily supplementation with 500 IU of vitamin D and 1,000 mg of calcium carbonate per day significantly improved bone mineral density, at a rate of 0.72% in the lumbar spine and 0.85% in the trochanter per year, compared with losses of 2% and 0.9%, respectively, among patients on placebo (Ann. Intern. Med. 1996;125:961-8).

In four prospective studies in 173 patients who recently started corticosteroid therapy, however, bone loss occurred at a rate of 3%-5% per year, despite daily supplementation with 500-800 mg of calcium.

Two other studies that Dr. Watts highlighted reported no bone loss in patients who were given up to 1,000 mg per day of calcium and up to 500 IU per day of vitamin D, although he noted that these patients had been on corticosteroid therapy for at least 1 year and in most cases almost 5 years.

“It's not clear to me how much of a role vitamin D and calcium will play in preventing bone loss,” he said.

Studies show that the risk for spinal fracture falls within a year or two of stopping therapy, although hip fracture risk remains increased over baseline.

Dr. Watts disclosed that he has relationships with Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., Sanofi-Aventis, Novo Nordisk Inc., and Novartis Pharmaceuticals Corp., which manufactures Reclast.

CHICAGO — Fracture risk increases in arthritis patients within about 3 months of starting corticosteroids and remains high, according to Dr. Nelson Watts.

“How much of this is steroids and how much of this is the underlying disease is unanswered,” said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati.

Glucocorticoid-induced osteoporosis results from a variety of systemic effects of corticosteroids, but it's the combination of reduced bone formation and increased bone resorption that causes a “double whammy” for patients—a troubling aspect for rheumatologists, who regularly dispense corticosteroids for their patients, Dr. Watts said at a symposium sponsored by the American College of Rheumatology.

The exact dose at which corticosteroids increase fracture risk is also difficult to tease out because of the underlying disease. One study observed that fracture risk was dose dependent and significantly higher with 2.5 mg/day or more of oral prednisone, with increases of 61% in hip and 160% in vertebral fractures (J. Bone Miner. Res. 2000;15:993-1000).

“It may well be that people who need 2.5 [mg]/day of prednisone are at increased risk for fracture not because of prednisone, but because of their rheumatoid arthritis; … clearly, as the dose goes up, the risk increases,” he said.

The American College of Rheumatology just began the process of revising its 2001 guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis. The current guidelines highlight lifestyle modifications, such as calcium and vitamin D supplementation, weight-bearing exercise, and minimization of alcohol intake.

There is at least one supportive trial for virtually all therapies, but several intervention trials have produced conflicting results for some agents, according to a recent review of glucocorticoids and the risk of osteoporosis (Expert Opin. Drug Saf. 2009;8:33-47).

The value of calcium and vitamin D supplementation is unclear, Dr. Watts said. In a relatively small trial in 96 RA patients on prednisone, daily supplementation with 500 IU of vitamin D and 1,000 mg of calcium carbonate per day significantly improved bone mineral density, at a rate of 0.72% in the lumbar spine and 0.85% in the trochanter per year, compared with losses of 2% and 0.9%, respectively, among patients on placebo (Ann. Intern. Med. 1996;125:961-8).

In four prospective studies in 173 patients who recently started corticosteroid therapy, however, bone loss occurred at a rate of 3%-5% per year, despite daily supplementation with 500-800 mg of calcium.

Two other studies that Dr. Watts highlighted reported no bone loss in patients who were given up to 1,000 mg per day of calcium and up to 500 IU per day of vitamin D, although he noted that these patients had been on corticosteroid therapy for at least 1 year and in most cases almost 5 years.

“It's not clear to me how much of a role vitamin D and calcium will play in preventing bone loss,” he said.

Studies show that the risk for spinal fracture falls within a year or two of stopping therapy, although hip fracture risk remains increased over baseline.

Dr. Watts disclosed that he has relationships with Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., Sanofi-Aventis, Novo Nordisk Inc., and Novartis Pharmaceuticals Corp., which manufactures Reclast.

SAN FRANCISCO — High-resolution MRI, multidetector CT, and high-resolution peripheral quantitative CT each may be useful in assessing bone quality, according to recent data.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine.

Trabecular and cortical bone structure are key components of bone quality, an important component of bone strength according to the National Institutes of Health (JAMA 2001;285:785–95).

In one randomized, double-blind study, for example, 51 postmenopausal women with osteopenia were treated with alendronate or placebo and followed over a 2-year period by 3T MRI of the radius, tibia, and femur; high-resolution peripheral quantitative CT (hr-pQCT) of the radius and tibia; and dual x-ray absorptiometry measures of bone mineral density. Both high-resolution MRI (hrMRI), and hr-pQCT results for trabecular bone showed moderate but significant correlation with bone density as a reference, even though there was a twofold to fourfold difference between hrMRI and hr-pQCT in parameter values such as trabecular number, thickness, or separation (J. Bone Miner. Res. 2008;23:463–74).

For corticol bone imaging, a newer area of research, two 2008 studies using hr-pQCT showed substantial differences between postmenopausal women with hip or wrist fractures, compared with fracture-free women, said Dr. Link, professor of radiology at the University of California, San Francisco.

Experimentally, hrMRI and hr-pQCT are being used to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences among normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. MRI or hr-pQCT provide high spatial resolution and produce no (or relatively little) radiation, compared with high-radiation exposure from multidetector CT. Multidetector CT allows imaging of more central skeletal sites, he said.

The hr-pQCT scanners image only peripheral sites, whereas hrMRI covers larger areas of the radius, tibia, and possibly the femur.

The CT techniques provide measures of bone densitometry. Although hrMRI gives no densitometric data, some studies suggest it may be used to analyze bone marrow composition through spectroscopy in order to assess bone stability. The three techniques appear to have similar rates of reproducibility.

MRI and hr-pQCT are expensive and prone to motion artifacts. Multidetector CT is available and requires less time for a scan. But postimage processing is challenging for MRI and CT.

Dr. Link reported receiving research funding and support from Merck & Co., which markets medication to treat osteoporosis.

The trabecular and cortical bone architecture in the distal tibia is shown in high-resolution peripheral quantitative CT (left) and high-resolution 3T MRI (right). Images courtesy Dr. Thomas M. Link

SAN FRANCISCO — High-resolution MRI, multidetector CT, and high-resolution peripheral quantitative CT each may be useful in assessing bone quality, according to recent data.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine.

Trabecular and cortical bone structure are key components of bone quality, an important component of bone strength according to the National Institutes of Health (JAMA 2001;285:785–95).

In one randomized, double-blind study, for example, 51 postmenopausal women with osteopenia were treated with alendronate or placebo and followed over a 2-year period by 3T MRI of the radius, tibia, and femur; high-resolution peripheral quantitative CT (hr-pQCT) of the radius and tibia; and dual x-ray absorptiometry measures of bone mineral density. Both high-resolution MRI (hrMRI), and hr-pQCT results for trabecular bone showed moderate but significant correlation with bone density as a reference, even though there was a twofold to fourfold difference between hrMRI and hr-pQCT in parameter values such as trabecular number, thickness, or separation (J. Bone Miner. Res. 2008;23:463–74).

For corticol bone imaging, a newer area of research, two 2008 studies using hr-pQCT showed substantial differences between postmenopausal women with hip or wrist fractures, compared with fracture-free women, said Dr. Link, professor of radiology at the University of California, San Francisco.

Experimentally, hrMRI and hr-pQCT are being used to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences among normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. MRI or hr-pQCT provide high spatial resolution and produce no (or relatively little) radiation, compared with high-radiation exposure from multidetector CT. Multidetector CT allows imaging of more central skeletal sites, he said.

The hr-pQCT scanners image only peripheral sites, whereas hrMRI covers larger areas of the radius, tibia, and possibly the femur.

The CT techniques provide measures of bone densitometry. Although hrMRI gives no densitometric data, some studies suggest it may be used to analyze bone marrow composition through spectroscopy in order to assess bone stability. The three techniques appear to have similar rates of reproducibility.

MRI and hr-pQCT are expensive and prone to motion artifacts. Multidetector CT is available and requires less time for a scan. But postimage processing is challenging for MRI and CT.

Dr. Link reported receiving research funding and support from Merck & Co., which markets medication to treat osteoporosis.

The trabecular and cortical bone architecture in the distal tibia is shown in high-resolution peripheral quantitative CT (left) and high-resolution 3T MRI (right). Images courtesy Dr. Thomas M. Link

SAN FRANCISCO — High-resolution MRI, multidetector CT, and high-resolution peripheral quantitative CT each may be useful in assessing bone quality, according to recent data.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine.

Trabecular and cortical bone structure are key components of bone quality, an important component of bone strength according to the National Institutes of Health (JAMA 2001;285:785–95).

In one randomized, double-blind study, for example, 51 postmenopausal women with osteopenia were treated with alendronate or placebo and followed over a 2-year period by 3T MRI of the radius, tibia, and femur; high-resolution peripheral quantitative CT (hr-pQCT) of the radius and tibia; and dual x-ray absorptiometry measures of bone mineral density. Both high-resolution MRI (hrMRI), and hr-pQCT results for trabecular bone showed moderate but significant correlation with bone density as a reference, even though there was a twofold to fourfold difference between hrMRI and hr-pQCT in parameter values such as trabecular number, thickness, or separation (J. Bone Miner. Res. 2008;23:463–74).

For corticol bone imaging, a newer area of research, two 2008 studies using hr-pQCT showed substantial differences between postmenopausal women with hip or wrist fractures, compared with fracture-free women, said Dr. Link, professor of radiology at the University of California, San Francisco.

Experimentally, hrMRI and hr-pQCT are being used to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences among normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. MRI or hr-pQCT provide high spatial resolution and produce no (or relatively little) radiation, compared with high-radiation exposure from multidetector CT. Multidetector CT allows imaging of more central skeletal sites, he said.

The hr-pQCT scanners image only peripheral sites, whereas hrMRI covers larger areas of the radius, tibia, and possibly the femur.

The CT techniques provide measures of bone densitometry. Although hrMRI gives no densitometric data, some studies suggest it may be used to analyze bone marrow composition through spectroscopy in order to assess bone stability. The three techniques appear to have similar rates of reproducibility.

MRI and hr-pQCT are expensive and prone to motion artifacts. Multidetector CT is available and requires less time for a scan. But postimage processing is challenging for MRI and CT.

Dr. Link reported receiving research funding and support from Merck & Co., which markets medication to treat osteoporosis.

The trabecular and cortical bone architecture in the distal tibia is shown in high-resolution peripheral quantitative CT (left) and high-resolution 3T MRI (right). Images courtesy Dr. Thomas M. Link