Osteoporosis

SAN DIEGO – Angiotensin-converting enzyme inhibitors may reduce the risk of age-related bone loss in elderly men.

A retrospective analysis of longitudinal data from the prospective Health ABC (Dynamics of Health, Aging and Body Composition Study) found that femoral neck bone mineral density was significantly greater in elderly men on an ACE inhibitor for 5 or more years for treatment of hypertension than in those who were not on long-term ACE inhibitor therapy, Dr. Nahid Rianon reported.

This secondary analysis of Health ABC involved 583 men with a mean age of 83 years. At 10-year follow-up, femoral neck bone mineral density was 0.04 g/cm

Of note, the same magnitude of improvement in femoral neck bone mineral density was seen after just 5 years of ACE inhibitor therapy. In other words, no further divergence in bone mineral density occurred during years 5-10.

Osteoporosis and hypertension are two major age-related chronic diseases that at present are managed separately using different classes of drugs. If ACE inhibitors can be shown to be beneficial in both of these extremely common diseases, management would be considerably simplified, observed Dr. Rianon of the University of Texas, Houston.

Health ABC is sponsored by the National Institute on Aging. Dr. Rianon declared having no financial conflicts.

SAN DIEGO – Angiotensin-converting enzyme inhibitors may reduce the risk of age-related bone loss in elderly men.

A retrospective analysis of longitudinal data from the prospective Health ABC (Dynamics of Health, Aging and Body Composition Study) found that femoral neck bone mineral density was significantly greater in elderly men on an ACE inhibitor for 5 or more years for treatment of hypertension than in those who were not on long-term ACE inhibitor therapy, Dr. Nahid Rianon reported.

This secondary analysis of Health ABC involved 583 men with a mean age of 83 years. At 10-year follow-up, femoral neck bone mineral density was 0.04 g/cm

Of note, the same magnitude of improvement in femoral neck bone mineral density was seen after just 5 years of ACE inhibitor therapy. In other words, no further divergence in bone mineral density occurred during years 5-10.

Osteoporosis and hypertension are two major age-related chronic diseases that at present are managed separately using different classes of drugs. If ACE inhibitors can be shown to be beneficial in both of these extremely common diseases, management would be considerably simplified, observed Dr. Rianon of the University of Texas, Houston.

Health ABC is sponsored by the National Institute on Aging. Dr. Rianon declared having no financial conflicts.

SAN DIEGO – Angiotensin-converting enzyme inhibitors may reduce the risk of age-related bone loss in elderly men.

A retrospective analysis of longitudinal data from the prospective Health ABC (Dynamics of Health, Aging and Body Composition Study) found that femoral neck bone mineral density was significantly greater in elderly men on an ACE inhibitor for 5 or more years for treatment of hypertension than in those who were not on long-term ACE inhibitor therapy, Dr. Nahid Rianon reported.

This secondary analysis of Health ABC involved 583 men with a mean age of 83 years. At 10-year follow-up, femoral neck bone mineral density was 0.04 g/cm

Of note, the same magnitude of improvement in femoral neck bone mineral density was seen after just 5 years of ACE inhibitor therapy. In other words, no further divergence in bone mineral density occurred during years 5-10.

Osteoporosis and hypertension are two major age-related chronic diseases that at present are managed separately using different classes of drugs. If ACE inhibitors can be shown to be beneficial in both of these extremely common diseases, management would be considerably simplified, observed Dr. Rianon of the University of Texas, Houston.

Health ABC is sponsored by the National Institute on Aging. Dr. Rianon declared having no financial conflicts.

SAN DIEGO – The widely used, Web-based fracture risk assessment tool known as FRAX seriously underestimates the risk of major osteoporotic and hip fractures in patients with diabetes, according to a large Canadian study.

This finding indicates diabetes is an independent risk factor for fractures above and beyond the risk factors incorporated in the FRAX tool, which include age, gender, smoking, fracture history, and glucocorticoid use – but not diabetes.

“One implication of our findings is that FRAX should be applied cautiously in clinical situations involving diabetic patients,” said Lora Giangregorio, Ph.D.

“Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors,” added Dr. Giangregorio of the University of Waterloo (Ontario).

She presented an analysis of a large Manitoba Province–wide database that included 3,518 patients with type 1 or type 2 diabetes and 36,085 nondiabetic controls, all at least 50 years old when they underwent bone mineral density testing during 1987-2008.

The FRAX tool was used to calculate 10-year fracture risk probabilities; actual incidence of major osteoporotic or hip fractures was determined through 2008.

The key finding: After the researchers controlled for FRAX fracture probability scores and use of osteoporotic medications, diabetes was independently associated with a 59% increased fracture rate in an average 10 years of follow-up.

Diabetes was a stronger predictor of hip fracture risk in younger subjects. Indeed, it was independently associated with a 5.3-fold increased risk of hip fracture in individuals younger than age 65, compared with a 2.1-fold increase in those who were older. In contrast, the risk of major osteoporotic fractures in diabetes patients was not related to age.

The fracture probability curves for diabetic and nondiabetic subjects diverged from the beginning of follow-up and continued to separate.

The study did not differentiate between type 1 and type 2 diabetes. However, in another study presented at the meeting, Dr. Ling Oei of Erasmus University, Rotterdam, the Netherlands, noted that type 2 diabetics are paradoxically at increased risk of osteoporotic fractures even though their BMD is typically normal or even increased.

In a prospective, population-based study of 203 patients with adequately controlled type 2 diabetes, 217 others with inadequately controlled disease, and 3,715 nondiabetic controls, Dr. Oei and coworkers showed that women with inadequately controlled diabetes had significantly lower BMD at both the lumbar spine and femoral neck, compared with women in the other two groups.

After the researchers controlled for age, femoral neck BMD, and body mass index, women with inadequately controlled type 2 diabetes had a 1.6-fold increased risk of fracture during an average 8.2-year follow-up, compared with patients who had adequately controlled type 2 diabetes or patients without diabetes, according to the Dutch investigators.

'Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors.'

Source DR. GIANGREGORIO

SAN DIEGO – The widely used, Web-based fracture risk assessment tool known as FRAX seriously underestimates the risk of major osteoporotic and hip fractures in patients with diabetes, according to a large Canadian study.

This finding indicates diabetes is an independent risk factor for fractures above and beyond the risk factors incorporated in the FRAX tool, which include age, gender, smoking, fracture history, and glucocorticoid use – but not diabetes.

“One implication of our findings is that FRAX should be applied cautiously in clinical situations involving diabetic patients,” said Lora Giangregorio, Ph.D.

“Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors,” added Dr. Giangregorio of the University of Waterloo (Ontario).

She presented an analysis of a large Manitoba Province–wide database that included 3,518 patients with type 1 or type 2 diabetes and 36,085 nondiabetic controls, all at least 50 years old when they underwent bone mineral density testing during 1987-2008.

The FRAX tool was used to calculate 10-year fracture risk probabilities; actual incidence of major osteoporotic or hip fractures was determined through 2008.

The key finding: After the researchers controlled for FRAX fracture probability scores and use of osteoporotic medications, diabetes was independently associated with a 59% increased fracture rate in an average 10 years of follow-up.

Diabetes was a stronger predictor of hip fracture risk in younger subjects. Indeed, it was independently associated with a 5.3-fold increased risk of hip fracture in individuals younger than age 65, compared with a 2.1-fold increase in those who were older. In contrast, the risk of major osteoporotic fractures in diabetes patients was not related to age.

The fracture probability curves for diabetic and nondiabetic subjects diverged from the beginning of follow-up and continued to separate.

The study did not differentiate between type 1 and type 2 diabetes. However, in another study presented at the meeting, Dr. Ling Oei of Erasmus University, Rotterdam, the Netherlands, noted that type 2 diabetics are paradoxically at increased risk of osteoporotic fractures even though their BMD is typically normal or even increased.

In a prospective, population-based study of 203 patients with adequately controlled type 2 diabetes, 217 others with inadequately controlled disease, and 3,715 nondiabetic controls, Dr. Oei and coworkers showed that women with inadequately controlled diabetes had significantly lower BMD at both the lumbar spine and femoral neck, compared with women in the other two groups.

After the researchers controlled for age, femoral neck BMD, and body mass index, women with inadequately controlled type 2 diabetes had a 1.6-fold increased risk of fracture during an average 8.2-year follow-up, compared with patients who had adequately controlled type 2 diabetes or patients without diabetes, according to the Dutch investigators.

'Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors.'

Source DR. GIANGREGORIO

SAN DIEGO – The widely used, Web-based fracture risk assessment tool known as FRAX seriously underestimates the risk of major osteoporotic and hip fractures in patients with diabetes, according to a large Canadian study.

This finding indicates diabetes is an independent risk factor for fractures above and beyond the risk factors incorporated in the FRAX tool, which include age, gender, smoking, fracture history, and glucocorticoid use – but not diabetes.

“One implication of our findings is that FRAX should be applied cautiously in clinical situations involving diabetic patients,” said Lora Giangregorio, Ph.D.

“Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors,” added Dr. Giangregorio of the University of Waterloo (Ontario).

She presented an analysis of a large Manitoba Province–wide database that included 3,518 patients with type 1 or type 2 diabetes and 36,085 nondiabetic controls, all at least 50 years old when they underwent bone mineral density testing during 1987-2008.

The FRAX tool was used to calculate 10-year fracture risk probabilities; actual incidence of major osteoporotic or hip fractures was determined through 2008.

The key finding: After the researchers controlled for FRAX fracture probability scores and use of osteoporotic medications, diabetes was independently associated with a 59% increased fracture rate in an average 10 years of follow-up.

Diabetes was a stronger predictor of hip fracture risk in younger subjects. Indeed, it was independently associated with a 5.3-fold increased risk of hip fracture in individuals younger than age 65, compared with a 2.1-fold increase in those who were older. In contrast, the risk of major osteoporotic fractures in diabetes patients was not related to age.

The fracture probability curves for diabetic and nondiabetic subjects diverged from the beginning of follow-up and continued to separate.

The study did not differentiate between type 1 and type 2 diabetes. However, in another study presented at the meeting, Dr. Ling Oei of Erasmus University, Rotterdam, the Netherlands, noted that type 2 diabetics are paradoxically at increased risk of osteoporotic fractures even though their BMD is typically normal or even increased.

In a prospective, population-based study of 203 patients with adequately controlled type 2 diabetes, 217 others with inadequately controlled disease, and 3,715 nondiabetic controls, Dr. Oei and coworkers showed that women with inadequately controlled diabetes had significantly lower BMD at both the lumbar spine and femoral neck, compared with women in the other two groups.

After the researchers controlled for age, femoral neck BMD, and body mass index, women with inadequately controlled type 2 diabetes had a 1.6-fold increased risk of fracture during an average 8.2-year follow-up, compared with patients who had adequately controlled type 2 diabetes or patients without diabetes, according to the Dutch investigators.

'Future iterations of the FRAX tool might consider adding diabetes to the list of risk factors.'

Source DR. GIANGREGORIO

CHICAGO – Denosumab remained well-tolerated, safe, and effective for maintaining reduced bone turnover and for increasing bone mineral density after 6 years of continuous use in 2,343 postmenopausal women with increased fracture risk due to osteoporosis.

These findings come from the first 3 years of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis) extension trial.

The fully human monoclonal antibody also led to significant gains in bone mineral density in a "crossover" group of 2,207 women who received placebo during the original FREEDOM trial – a pivotal trial published in 2009 that demonstrated a favorable risk/benefit profile for denosumab (N. Engl. J. Med. 2009;361:756-65).

The agent subsequently received Food and Drug Administration approval for the treatment of postmenopausal women with osteoporosis and an increased fracture risk.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group.

During the open-label active treatment extension trial, which was designed to investigate the efficacy and safety of the drug for up to 10 years, participants received 60 mg of denosumab as a subcutaneous injection every 6 months along with daily supplemental calcium and vitamin D. In the first 3 years of the extension trial, those in the long-term treatment group experienced additional, statistically significant increases in bone mineral density (cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip), and those in the crossover group experienced significant mean gains in bone mineral density that were similar to those seen initially in the FREEDOM trial active treatment group (9.4% at the lumbar spine and 4.8% at the total hip), Dr. Jacques P. Brown reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The gains seen in the active treatment group in the FREEDOM trial at 3 years were 10.1% at the lumbar spine and 5.7% at the total hip, said Dr. Brown of Laval University, Quebec City.

Measures of serum carboxy-terminal telopeptide (CTX), which is a marker of bone resorption, demonstrated "a profound reduction in bone resorption" appearing rapidly and similarly after the first treatment in the cross-over group, and after the seventh treatment in the long-term treatment group – with the "characteristic attenuation observed at the end of the dosing period," Dr. Brown said.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group. Fracture incidence also remained low in the long-term group in the extension trial, he said, noting that adverse events and serious adverse events also did not increase over time in the extension trial, and there were no "significant imbalances between the groups."

Osteonecrosis of the jaw occurred in two patients in both the long-term and crossover treatment groups; in the crossover group, both cases resolved completely within the follow-up period, and one of those patients had continued on treatment. The cases in the long-term treatment group remained unresolved at the time of Dr. Brown’s report.

These interim findings from the FREEDOM extension trial demonstrate that denosumab treatment for up to 6 years lead to continued improvement in women on long-term treatment, and that treatment for up to 3 years in the crossover group largely reproduced the observations in the original FREEDOM denosumab group, Dr. Brown concluded.

Dr. Brown disclosed having various relationships with Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. Other authors on the study also disclosed various relationships with these and/or other pharmaceutical companies.

CHICAGO – Denosumab remained well-tolerated, safe, and effective for maintaining reduced bone turnover and for increasing bone mineral density after 6 years of continuous use in 2,343 postmenopausal women with increased fracture risk due to osteoporosis.

These findings come from the first 3 years of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis) extension trial.

The fully human monoclonal antibody also led to significant gains in bone mineral density in a "crossover" group of 2,207 women who received placebo during the original FREEDOM trial – a pivotal trial published in 2009 that demonstrated a favorable risk/benefit profile for denosumab (N. Engl. J. Med. 2009;361:756-65).

The agent subsequently received Food and Drug Administration approval for the treatment of postmenopausal women with osteoporosis and an increased fracture risk.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group.

During the open-label active treatment extension trial, which was designed to investigate the efficacy and safety of the drug for up to 10 years, participants received 60 mg of denosumab as a subcutaneous injection every 6 months along with daily supplemental calcium and vitamin D. In the first 3 years of the extension trial, those in the long-term treatment group experienced additional, statistically significant increases in bone mineral density (cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip), and those in the crossover group experienced significant mean gains in bone mineral density that were similar to those seen initially in the FREEDOM trial active treatment group (9.4% at the lumbar spine and 4.8% at the total hip), Dr. Jacques P. Brown reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The gains seen in the active treatment group in the FREEDOM trial at 3 years were 10.1% at the lumbar spine and 5.7% at the total hip, said Dr. Brown of Laval University, Quebec City.

Measures of serum carboxy-terminal telopeptide (CTX), which is a marker of bone resorption, demonstrated "a profound reduction in bone resorption" appearing rapidly and similarly after the first treatment in the cross-over group, and after the seventh treatment in the long-term treatment group – with the "characteristic attenuation observed at the end of the dosing period," Dr. Brown said.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group. Fracture incidence also remained low in the long-term group in the extension trial, he said, noting that adverse events and serious adverse events also did not increase over time in the extension trial, and there were no "significant imbalances between the groups."

Osteonecrosis of the jaw occurred in two patients in both the long-term and crossover treatment groups; in the crossover group, both cases resolved completely within the follow-up period, and one of those patients had continued on treatment. The cases in the long-term treatment group remained unresolved at the time of Dr. Brown’s report.

These interim findings from the FREEDOM extension trial demonstrate that denosumab treatment for up to 6 years lead to continued improvement in women on long-term treatment, and that treatment for up to 3 years in the crossover group largely reproduced the observations in the original FREEDOM denosumab group, Dr. Brown concluded.

Dr. Brown disclosed having various relationships with Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. Other authors on the study also disclosed various relationships with these and/or other pharmaceutical companies.

CHICAGO – Denosumab remained well-tolerated, safe, and effective for maintaining reduced bone turnover and for increasing bone mineral density after 6 years of continuous use in 2,343 postmenopausal women with increased fracture risk due to osteoporosis.

These findings come from the first 3 years of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis) extension trial.

The fully human monoclonal antibody also led to significant gains in bone mineral density in a "crossover" group of 2,207 women who received placebo during the original FREEDOM trial – a pivotal trial published in 2009 that demonstrated a favorable risk/benefit profile for denosumab (N. Engl. J. Med. 2009;361:756-65).

The agent subsequently received Food and Drug Administration approval for the treatment of postmenopausal women with osteoporosis and an increased fracture risk.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group.

During the open-label active treatment extension trial, which was designed to investigate the efficacy and safety of the drug for up to 10 years, participants received 60 mg of denosumab as a subcutaneous injection every 6 months along with daily supplemental calcium and vitamin D. In the first 3 years of the extension trial, those in the long-term treatment group experienced additional, statistically significant increases in bone mineral density (cumulative 6-year gains of 15.2% at the lumbar spine and 7.5% at the total hip), and those in the crossover group experienced significant mean gains in bone mineral density that were similar to those seen initially in the FREEDOM trial active treatment group (9.4% at the lumbar spine and 4.8% at the total hip), Dr. Jacques P. Brown reported during a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

The gains seen in the active treatment group in the FREEDOM trial at 3 years were 10.1% at the lumbar spine and 5.7% at the total hip, said Dr. Brown of Laval University, Quebec City.

Measures of serum carboxy-terminal telopeptide (CTX), which is a marker of bone resorption, demonstrated "a profound reduction in bone resorption" appearing rapidly and similarly after the first treatment in the cross-over group, and after the seventh treatment in the long-term treatment group – with the "characteristic attenuation observed at the end of the dosing period," Dr. Brown said.

The annual incidences of new vertebral and nonvertebral fractures were lower in the crossover group in the extension trial than in the FREEDOM placebo group. Fracture incidence also remained low in the long-term group in the extension trial, he said, noting that adverse events and serious adverse events also did not increase over time in the extension trial, and there were no "significant imbalances between the groups."

Osteonecrosis of the jaw occurred in two patients in both the long-term and crossover treatment groups; in the crossover group, both cases resolved completely within the follow-up period, and one of those patients had continued on treatment. The cases in the long-term treatment group remained unresolved at the time of Dr. Brown’s report.

These interim findings from the FREEDOM extension trial demonstrate that denosumab treatment for up to 6 years lead to continued improvement in women on long-term treatment, and that treatment for up to 3 years in the crossover group largely reproduced the observations in the original FREEDOM denosumab group, Dr. Brown concluded.

Dr. Brown disclosed having various relationships with Abbott, Amgen, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Servier, and Warner Chilcott. Other authors on the study also disclosed various relationships with these and/or other pharmaceutical companies.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they have had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, who is medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a fall in the future by three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the conference, sponsored by the University of California, San Francisco.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling, he said.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials involving 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards were effective, Dr. Pierluissi noted.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls association with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study. Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early because of lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413-22).

Dr. Pierluissi said that he had no relevant conflicts of interest.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they have had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, who is medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a fall in the future by three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the conference, sponsored by the University of California, San Francisco.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling, he said.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials involving 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards were effective, Dr. Pierluissi noted.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls association with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study. Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early because of lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413-22).

Dr. Pierluissi said that he had no relevant conflicts of interest.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they have had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, who is medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a fall in the future by three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the conference, sponsored by the University of California, San Francisco.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling, he said.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials involving 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards were effective, Dr. Pierluissi noted.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls association with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study. Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early because of lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413-22).

Dr. Pierluissi said that he had no relevant conflicts of interest.

Major Finding: Discharge of kidney transplant recipients on corticosteroid-based immunosuppression was independently associated with a 45% increased risk in major fractures over the next 4 years compared to patients managed with early corticosteroid withdrawal while still in-hospital.

Data Source: Retrospective analysis of nearly 78,000 kidney transplant recipients in the United States Renal System database.

Disclosures: Dr. Nikkel declared having no financial conflicts.

SAN DIEGO – Early corticosteroid withdrawal after kidney transplantation is associated with a marked reduction in major fracture rate, according to an analysis of the United States Renal Data System database.

Indeed, discharge on corticosteroids was independently associated with a 45% increased risk of major fractures requiring hospitalization during a median follow-up of about 4 years, Dr. Lucas Nikkel reported at the meeting.

Early corticosteroid withdrawal regimens are gaining popularity at renal transplant centers as a means of reducing a wide range of immunosuppression-related side effects. The documented major clinical advantages include reduced rates of hyperlipidemia, posttransplant diabetes, cardiovascular events, infections, and cancer. Until now, however, no study had examined whether early corticosteroid withdrawal regimens are also effective in reducing fracture incidence, noted Dr. Nikkel, who earned the ASBMR Young Investigator Award for his work.

Early corticosteroid withdrawal regimens consist of 4-7 days of high-dose methylprednisolone administered at the time of transplantation, followed by withdrawal of the drug in favor of long-term immunosuppression with calcineurin inhibitors and mycophenolic acid. More than 30% of kidney transplant recipients in the United States are now managed using such protocols.

Dr. Nikkel identified 77,625 adults in the USRDS database who received a kidney transplant during 2000-2006. Pretransplant fracture rates were similar in the 11,178 patients not on steroids at discharge and the 66,447 who were.

The incidence of fractures requiring hospitalization during the follow-up period was 1.7% in patients with early corticosteroid withdrawal, significantly less than the 3.3% for those discharged on corticosteroid-based immunosuppression. The rate was 5.8 major fractures per 1,000 patient-years in the early steroid withdrawal group, compared with 8.0 per 1,000 patient-years in those on corticosteroid-based immunosuppression. The increased fracture risk in patients discharged on steroids became apparent at 1 year of follow-up and significant at 2 years.

“It's noteworthy that patients in the youngest age group discharged on corticosteroids had a similar risk of fractures compared to the oldest patients discharged without corticosteroids,” observed Dr. Nikkel, who is with Columbia University, New York.

In addition to discharge on steroids, other fracture risk factors identified in the study included older age, female gender, white race, pretransplant diabetes, a positive fracture history, and being on dialysis.

Since most fractures are treated on an outpatient basis, it is likely that these study results greatly underestimate the true fracture burden that is associated with kidney transplantation, he added.

Dr. Nikkel pointed out that his study was a retrospective analysis of observational data and said that prospective, long-term studies are needed to confirm the results.

Each year, more than 17,000 kidney transplants are performed in the United States, and more than 68,000 worldwide. Bone loss is high in these patients, especially in the first 18 months after transplantation.

Kidney transplant recipients have a 4.5-fold greater fracture risk than do the general population and a 30% greater risk than do hemodialysis patients during the first 3 years post transplant.

Audience members said that there is evidence to suggest calcineurin inhibitors adversely affect bone health as well, and they urged Dr. Nikkel to extend his follow-up to monitor this situation.

Younger patients given steroids had a risk similar to older patients discharged without corticosteroids.

Source DR. NIKKEL

Major Finding: Discharge of kidney transplant recipients on corticosteroid-based immunosuppression was independently associated with a 45% increased risk in major fractures over the next 4 years compared to patients managed with early corticosteroid withdrawal while still in-hospital.

Data Source: Retrospective analysis of nearly 78,000 kidney transplant recipients in the United States Renal System database.

Disclosures: Dr. Nikkel declared having no financial conflicts.

SAN DIEGO – Early corticosteroid withdrawal after kidney transplantation is associated with a marked reduction in major fracture rate, according to an analysis of the United States Renal Data System database.

Indeed, discharge on corticosteroids was independently associated with a 45% increased risk of major fractures requiring hospitalization during a median follow-up of about 4 years, Dr. Lucas Nikkel reported at the meeting.

Early corticosteroid withdrawal regimens are gaining popularity at renal transplant centers as a means of reducing a wide range of immunosuppression-related side effects. The documented major clinical advantages include reduced rates of hyperlipidemia, posttransplant diabetes, cardiovascular events, infections, and cancer. Until now, however, no study had examined whether early corticosteroid withdrawal regimens are also effective in reducing fracture incidence, noted Dr. Nikkel, who earned the ASBMR Young Investigator Award for his work.

Early corticosteroid withdrawal regimens consist of 4-7 days of high-dose methylprednisolone administered at the time of transplantation, followed by withdrawal of the drug in favor of long-term immunosuppression with calcineurin inhibitors and mycophenolic acid. More than 30% of kidney transplant recipients in the United States are now managed using such protocols.

Dr. Nikkel identified 77,625 adults in the USRDS database who received a kidney transplant during 2000-2006. Pretransplant fracture rates were similar in the 11,178 patients not on steroids at discharge and the 66,447 who were.

The incidence of fractures requiring hospitalization during the follow-up period was 1.7% in patients with early corticosteroid withdrawal, significantly less than the 3.3% for those discharged on corticosteroid-based immunosuppression. The rate was 5.8 major fractures per 1,000 patient-years in the early steroid withdrawal group, compared with 8.0 per 1,000 patient-years in those on corticosteroid-based immunosuppression. The increased fracture risk in patients discharged on steroids became apparent at 1 year of follow-up and significant at 2 years.

“It's noteworthy that patients in the youngest age group discharged on corticosteroids had a similar risk of fractures compared to the oldest patients discharged without corticosteroids,” observed Dr. Nikkel, who is with Columbia University, New York.

In addition to discharge on steroids, other fracture risk factors identified in the study included older age, female gender, white race, pretransplant diabetes, a positive fracture history, and being on dialysis.

Since most fractures are treated on an outpatient basis, it is likely that these study results greatly underestimate the true fracture burden that is associated with kidney transplantation, he added.

Dr. Nikkel pointed out that his study was a retrospective analysis of observational data and said that prospective, long-term studies are needed to confirm the results.

Each year, more than 17,000 kidney transplants are performed in the United States, and more than 68,000 worldwide. Bone loss is high in these patients, especially in the first 18 months after transplantation.

Kidney transplant recipients have a 4.5-fold greater fracture risk than do the general population and a 30% greater risk than do hemodialysis patients during the first 3 years post transplant.

Audience members said that there is evidence to suggest calcineurin inhibitors adversely affect bone health as well, and they urged Dr. Nikkel to extend his follow-up to monitor this situation.

Younger patients given steroids had a risk similar to older patients discharged without corticosteroids.

Source DR. NIKKEL

Major Finding: Discharge of kidney transplant recipients on corticosteroid-based immunosuppression was independently associated with a 45% increased risk in major fractures over the next 4 years compared to patients managed with early corticosteroid withdrawal while still in-hospital.

Data Source: Retrospective analysis of nearly 78,000 kidney transplant recipients in the United States Renal System database.

Disclosures: Dr. Nikkel declared having no financial conflicts.

SAN DIEGO – Early corticosteroid withdrawal after kidney transplantation is associated with a marked reduction in major fracture rate, according to an analysis of the United States Renal Data System database.

Indeed, discharge on corticosteroids was independently associated with a 45% increased risk of major fractures requiring hospitalization during a median follow-up of about 4 years, Dr. Lucas Nikkel reported at the meeting.

Early corticosteroid withdrawal regimens are gaining popularity at renal transplant centers as a means of reducing a wide range of immunosuppression-related side effects. The documented major clinical advantages include reduced rates of hyperlipidemia, posttransplant diabetes, cardiovascular events, infections, and cancer. Until now, however, no study had examined whether early corticosteroid withdrawal regimens are also effective in reducing fracture incidence, noted Dr. Nikkel, who earned the ASBMR Young Investigator Award for his work.

Early corticosteroid withdrawal regimens consist of 4-7 days of high-dose methylprednisolone administered at the time of transplantation, followed by withdrawal of the drug in favor of long-term immunosuppression with calcineurin inhibitors and mycophenolic acid. More than 30% of kidney transplant recipients in the United States are now managed using such protocols.

Dr. Nikkel identified 77,625 adults in the USRDS database who received a kidney transplant during 2000-2006. Pretransplant fracture rates were similar in the 11,178 patients not on steroids at discharge and the 66,447 who were.

The incidence of fractures requiring hospitalization during the follow-up period was 1.7% in patients with early corticosteroid withdrawal, significantly less than the 3.3% for those discharged on corticosteroid-based immunosuppression. The rate was 5.8 major fractures per 1,000 patient-years in the early steroid withdrawal group, compared with 8.0 per 1,000 patient-years in those on corticosteroid-based immunosuppression. The increased fracture risk in patients discharged on steroids became apparent at 1 year of follow-up and significant at 2 years.

“It's noteworthy that patients in the youngest age group discharged on corticosteroids had a similar risk of fractures compared to the oldest patients discharged without corticosteroids,” observed Dr. Nikkel, who is with Columbia University, New York.

In addition to discharge on steroids, other fracture risk factors identified in the study included older age, female gender, white race, pretransplant diabetes, a positive fracture history, and being on dialysis.

Since most fractures are treated on an outpatient basis, it is likely that these study results greatly underestimate the true fracture burden that is associated with kidney transplantation, he added.

Dr. Nikkel pointed out that his study was a retrospective analysis of observational data and said that prospective, long-term studies are needed to confirm the results.

Each year, more than 17,000 kidney transplants are performed in the United States, and more than 68,000 worldwide. Bone loss is high in these patients, especially in the first 18 months after transplantation.

Kidney transplant recipients have a 4.5-fold greater fracture risk than do the general population and a 30% greater risk than do hemodialysis patients during the first 3 years post transplant.

Audience members said that there is evidence to suggest calcineurin inhibitors adversely affect bone health as well, and they urged Dr. Nikkel to extend his follow-up to monitor this situation.

Younger patients given steroids had a risk similar to older patients discharged without corticosteroids.

Source DR. NIKKEL

Major Finding: During an average 7.3 years of treatment and follow-up, the overall nonvertebral fracture incidence was 7.6% in the supplementation group, compared with 6.9% in placebo-treated controls.

Data Source: Secondary analysis of the 5,442-subject randomized, double-blind, placebo-controlled Women's Antioxidant and Folic Acid Cardiovascular Study.

Disclosures: WAFACS was funded by the National Heart, Lung, and Blood Institute. Dr. Bauer reported having no financial conflicts.

SAN DIEGO – Combined daily supplementation with folic acid and vitamins B₆ and B₁₂ proved to be a bust for reduction of nonvertebral fracture risk in a large, randomized, double-blind clinical trial conducted in women with known cardiovascular disease or multiple risk factors.

A secondary analysis of fracture outcomes in 5,442 female health professionals over age 42 years who participated in the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS) showed an overall nonvertebral fracture incidence of 7.6% during an average 7.3 years of treatment and follow-up in the supplementation group and a similar 6.9% rate in placebo-treated controls, Dr. Douglas C. Bauer reported at the meeting.

Participants in WAFACS had known cardiovascular disease or at least three cardiovascular risk factors. The previously reported primary study end points were cardiovascular event rates and all-cause mortality, where supplements had no effect (JAMA 2008;299:2027-36).

The new retrospective secondary analysis of WAFACS was undertaken because some prior observational studies had concluded that elevated homocysteine and low vitamin B₁₂ levels are associated with increased fracture risk. The supplement regimen utilized in the trial was designed to lower homocysteine and boost vitamin B₁₂ levels. It consisted of daily folic acid at 2.5 mg, vitamin B₆ at 50 mg, and vitamin B₁₂ at 1 mg.

In all, 80% of participants reported greater than 66% compliance with therapy. Rates of hip, wrist, and total nonspine fractures were similar in both high-compliance subgroups, noted Dr. Bauer of the University of California, San Francisco.

Major Finding: During an average 7.3 years of treatment and follow-up, the overall nonvertebral fracture incidence was 7.6% in the supplementation group, compared with 6.9% in placebo-treated controls.

Data Source: Secondary analysis of the 5,442-subject randomized, double-blind, placebo-controlled Women's Antioxidant and Folic Acid Cardiovascular Study.

Disclosures: WAFACS was funded by the National Heart, Lung, and Blood Institute. Dr. Bauer reported having no financial conflicts.

SAN DIEGO – Combined daily supplementation with folic acid and vitamins B₆ and B₁₂ proved to be a bust for reduction of nonvertebral fracture risk in a large, randomized, double-blind clinical trial conducted in women with known cardiovascular disease or multiple risk factors.

A secondary analysis of fracture outcomes in 5,442 female health professionals over age 42 years who participated in the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS) showed an overall nonvertebral fracture incidence of 7.6% during an average 7.3 years of treatment and follow-up in the supplementation group and a similar 6.9% rate in placebo-treated controls, Dr. Douglas C. Bauer reported at the meeting.

Participants in WAFACS had known cardiovascular disease or at least three cardiovascular risk factors. The previously reported primary study end points were cardiovascular event rates and all-cause mortality, where supplements had no effect (JAMA 2008;299:2027-36).

The new retrospective secondary analysis of WAFACS was undertaken because some prior observational studies had concluded that elevated homocysteine and low vitamin B₁₂ levels are associated with increased fracture risk. The supplement regimen utilized in the trial was designed to lower homocysteine and boost vitamin B₁₂ levels. It consisted of daily folic acid at 2.5 mg, vitamin B₆ at 50 mg, and vitamin B₁₂ at 1 mg.

In all, 80% of participants reported greater than 66% compliance with therapy. Rates of hip, wrist, and total nonspine fractures were similar in both high-compliance subgroups, noted Dr. Bauer of the University of California, San Francisco.

Major Finding: During an average 7.3 years of treatment and follow-up, the overall nonvertebral fracture incidence was 7.6% in the supplementation group, compared with 6.9% in placebo-treated controls.

Data Source: Secondary analysis of the 5,442-subject randomized, double-blind, placebo-controlled Women's Antioxidant and Folic Acid Cardiovascular Study.

Disclosures: WAFACS was funded by the National Heart, Lung, and Blood Institute. Dr. Bauer reported having no financial conflicts.

SAN DIEGO – Combined daily supplementation with folic acid and vitamins B₆ and B₁₂ proved to be a bust for reduction of nonvertebral fracture risk in a large, randomized, double-blind clinical trial conducted in women with known cardiovascular disease or multiple risk factors.

A secondary analysis of fracture outcomes in 5,442 female health professionals over age 42 years who participated in the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS) showed an overall nonvertebral fracture incidence of 7.6% during an average 7.3 years of treatment and follow-up in the supplementation group and a similar 6.9% rate in placebo-treated controls, Dr. Douglas C. Bauer reported at the meeting.

Participants in WAFACS had known cardiovascular disease or at least three cardiovascular risk factors. The previously reported primary study end points were cardiovascular event rates and all-cause mortality, where supplements had no effect (JAMA 2008;299:2027-36).

The new retrospective secondary analysis of WAFACS was undertaken because some prior observational studies had concluded that elevated homocysteine and low vitamin B₁₂ levels are associated with increased fracture risk. The supplement regimen utilized in the trial was designed to lower homocysteine and boost vitamin B₁₂ levels. It consisted of daily folic acid at 2.5 mg, vitamin B₆ at 50 mg, and vitamin B₁₂ at 1 mg.

In all, 80% of participants reported greater than 66% compliance with therapy. Rates of hip, wrist, and total nonspine fractures were similar in both high-compliance subgroups, noted Dr. Bauer of the University of California, San Francisco.

SAN DIEGO – Teriparatide has received a boost in status as a preferentially effective treatment for glucocorticoid-induced osteoporosis in the form of a second, confirmatory, randomized double-blind trial demonstrating the anabolic agent achieves substantially greater increases in bone mineral density compared to a bisphosphonate.

One of these studies also included fracture rates as a preplanned secondary end point; the trial showed a significant reduction in vertebral fractures with teriparatide (Forteo) as compared to alendronate (Fosamax).

These positive study findings are bolstered by a biologically plausible mechanism of benefit, observed Dr. Kenneth G. Saag. “Based upon the pathogenesis of glucocorticoid-induced osteoporosis [GIOP], we think that an anabolic agent makes some sense. It may be beneficial to stimulate osteoblasts to promote new bone formation,” said Dr. Saag, professor of medicine and epidemiology at the University of Alabama at Birmingham.

Steroids are known to have apoptosis-mediated deleterious effects on both osteocytes and osteoblasts that lead to decline in bone function and an abrupt increase in fracture risk independent of bone mineral density (BMD). Osteoclasts are also unfavorably impacted because of cross talk and the indirect effects of sex steroids, insulin-like growth factor, and a modest effect of secondary hyperparathyroidism mediated through altered calcium absorption. In addition, higher-dose steroids have adverse effects upon muscle that can independently lead to a higher fracture rate, he explained.

The Food and Drug Administration has approved alendronate, zoledronic acid (Reclast), risedronate (Actonel), and teriparatide (Forteo) for treatment of GIOP. More recently, raloxifene (Evista) has joined the ranks of agents shown to increase BMD in patients on long-term steroids; this came in the form of a double-blind, placebo-controlled, 12-month study (Ann. Rheum. Dis. 2011;70:778-84).

Subcutaneous daily teriparatide for up to 2 years also has the approval of the FDA for use in adults at high fracture risk because they are on sustained systemic steroid therapy.

There is no definitive study demonstrating that any of these agents actually prevents fractures in patients with GIOP.

However, data from a study in which Dr. Saag was lead investigator showed that teriparatide-treated patients had significantly fewer vertebral fractures than those assigned to alendronate. The study was a 36-month randomized, double-blind, clinical trial that assessed fracture rates as a preplanned secondary end point. The radiographic and clinical vertebral fracture rates in 169 alendronate-treated patients were 7.7% and 2.4%, respectively, compared with 1.7% and 0% in 173 teriparatide-treated patients (P = .007 and .037). No significant difference in nonvertebral fractures was found between the two treatment arms.

The primary study end point was the change in BMD from baseline. Here again teriparatide proved significantly more effective than the bisphosphonate, with a mean 11% increase at the lumbar spine, compared to 5.3% with alendronate.

Teriparatide-treated patients also had a 5.2% increase in BMD at the total hip and a 6.3% boost at the femoral neck, compared to 2.7% and 3.4%, respectively, with alendronate (Arthritis Rheum. 2009;60:3346-55).

Confirmation of teriparatide's superior BMD-building effect came from the EuroGIOPs trial presented by Dr. Claus C. Glüer at the ASBMR meeting.

EuroGIOPS was an 18-month, open-label, phase III clinical trial in which 92 men with GIOP were randomized to teriparatide or risedronate.

At 6 months the mean increase in lumbar spine BMD was 5.7% in the teriparatide group, compared with 3.3% in the risedronate arm.

At 18 months – the primary study end point – the teriparatide group averaged a 16.3% BMD increase over baseline, while the risedronate arm had a 3.8% rise.

Intriguingly, new clinical fractures occurred during 18 months of therapy in five patients on risedronate and none on teriparatide, a difference that came within a hair of statistical significance (P = .056).

Bone strength as formally measured in terms of anterior bending, axial compression, and axial torsion was also significantly greater in the teriparatide group, according to Dr. Glüer, who is professor of medical physics at the department of diagnostic radiology, University Hospital Schleswig-Holstein in Kiel, Germany.

The 2010 update of the American College of Rheumatology guidelines for the prevention and treatment of GIOP recommend bisphosphonates but not teriparatide for older adults at high risk of fracture who are taking less than 5 mg/day of prednisone for less than 1 month (Arthritis Care Res. 2010;62:1515-26).

The ACR guidelines recommend reserving use of teriparatide for high-risk patients – that is, those with a prevalent fracture or a World Health Organization Fracture Risk Assessment Tool (FRAX) score indicative of a greater than 20% 10-year risk of a major osteoporotic fracture – who are on at least 6 mg/day of prednisone for less than 1 month or on any dose of glucocorticoids for longer than 1 month.

Although Dr. Saag was a coauthor of the ACR guidelines, he was pleased to see a new commentary on the ACR guidelines published by the Professional Practice Committee of the ASBMR. The review recommends teriparatide or any of the bisphosphonates for high-risk patients, period.

Dr. Saag, who was not involved in the ASBMR review, recommended it as useful reading both for its areas of agreement with the ACR guidelines as well as for raising several patient scenarios in which the ASBMR committee believes the ACR recommendations either do not apply or might be improved upon (J. Bone Miner. Res. 2011;26:1989-96).

Dr. Glüer declared having no financial conflicts regarding the Eli Lilly–funded EuroGIOPs trial. Dr. Saag disclosed that he has received research grants from and serves as a paid consultant to Amgen, Eli Lilly, Merck, and Novartis.

Dr. Kenneth G. Saag noted that an anabolic agent such as teriparatide stimulates osteoblasts to promote new bone formation.

Source Courtesy University of Alabama

SAN DIEGO – Teriparatide has received a boost in status as a preferentially effective treatment for glucocorticoid-induced osteoporosis in the form of a second, confirmatory, randomized double-blind trial demonstrating the anabolic agent achieves substantially greater increases in bone mineral density compared to a bisphosphonate.

One of these studies also included fracture rates as a preplanned secondary end point; the trial showed a significant reduction in vertebral fractures with teriparatide (Forteo) as compared to alendronate (Fosamax).

These positive study findings are bolstered by a biologically plausible mechanism of benefit, observed Dr. Kenneth G. Saag. “Based upon the pathogenesis of glucocorticoid-induced osteoporosis [GIOP], we think that an anabolic agent makes some sense. It may be beneficial to stimulate osteoblasts to promote new bone formation,” said Dr. Saag, professor of medicine and epidemiology at the University of Alabama at Birmingham.

Steroids are known to have apoptosis-mediated deleterious effects on both osteocytes and osteoblasts that lead to decline in bone function and an abrupt increase in fracture risk independent of bone mineral density (BMD). Osteoclasts are also unfavorably impacted because of cross talk and the indirect effects of sex steroids, insulin-like growth factor, and a modest effect of secondary hyperparathyroidism mediated through altered calcium absorption. In addition, higher-dose steroids have adverse effects upon muscle that can independently lead to a higher fracture rate, he explained.

The Food and Drug Administration has approved alendronate, zoledronic acid (Reclast), risedronate (Actonel), and teriparatide (Forteo) for treatment of GIOP. More recently, raloxifene (Evista) has joined the ranks of agents shown to increase BMD in patients on long-term steroids; this came in the form of a double-blind, placebo-controlled, 12-month study (Ann. Rheum. Dis. 2011;70:778-84).

Subcutaneous daily teriparatide for up to 2 years also has the approval of the FDA for use in adults at high fracture risk because they are on sustained systemic steroid therapy.

There is no definitive study demonstrating that any of these agents actually prevents fractures in patients with GIOP.

However, data from a study in which Dr. Saag was lead investigator showed that teriparatide-treated patients had significantly fewer vertebral fractures than those assigned to alendronate. The study was a 36-month randomized, double-blind, clinical trial that assessed fracture rates as a preplanned secondary end point. The radiographic and clinical vertebral fracture rates in 169 alendronate-treated patients were 7.7% and 2.4%, respectively, compared with 1.7% and 0% in 173 teriparatide-treated patients (P = .007 and .037). No significant difference in nonvertebral fractures was found between the two treatment arms.

The primary study end point was the change in BMD from baseline. Here again teriparatide proved significantly more effective than the bisphosphonate, with a mean 11% increase at the lumbar spine, compared to 5.3% with alendronate.

Teriparatide-treated patients also had a 5.2% increase in BMD at the total hip and a 6.3% boost at the femoral neck, compared to 2.7% and 3.4%, respectively, with alendronate (Arthritis Rheum. 2009;60:3346-55).

Confirmation of teriparatide's superior BMD-building effect came from the EuroGIOPs trial presented by Dr. Claus C. Glüer at the ASBMR meeting.

EuroGIOPS was an 18-month, open-label, phase III clinical trial in which 92 men with GIOP were randomized to teriparatide or risedronate.

At 6 months the mean increase in lumbar spine BMD was 5.7% in the teriparatide group, compared with 3.3% in the risedronate arm.

At 18 months – the primary study end point – the teriparatide group averaged a 16.3% BMD increase over baseline, while the risedronate arm had a 3.8% rise.

Intriguingly, new clinical fractures occurred during 18 months of therapy in five patients on risedronate and none on teriparatide, a difference that came within a hair of statistical significance (P = .056).

Bone strength as formally measured in terms of anterior bending, axial compression, and axial torsion was also significantly greater in the teriparatide group, according to Dr. Glüer, who is professor of medical physics at the department of diagnostic radiology, University Hospital Schleswig-Holstein in Kiel, Germany.

The 2010 update of the American College of Rheumatology guidelines for the prevention and treatment of GIOP recommend bisphosphonates but not teriparatide for older adults at high risk of fracture who are taking less than 5 mg/day of prednisone for less than 1 month (Arthritis Care Res. 2010;62:1515-26).

The ACR guidelines recommend reserving use of teriparatide for high-risk patients – that is, those with a prevalent fracture or a World Health Organization Fracture Risk Assessment Tool (FRAX) score indicative of a greater than 20% 10-year risk of a major osteoporotic fracture – who are on at least 6 mg/day of prednisone for less than 1 month or on any dose of glucocorticoids for longer than 1 month.

Although Dr. Saag was a coauthor of the ACR guidelines, he was pleased to see a new commentary on the ACR guidelines published by the Professional Practice Committee of the ASBMR. The review recommends teriparatide or any of the bisphosphonates for high-risk patients, period.

Dr. Saag, who was not involved in the ASBMR review, recommended it as useful reading both for its areas of agreement with the ACR guidelines as well as for raising several patient scenarios in which the ASBMR committee believes the ACR recommendations either do not apply or might be improved upon (J. Bone Miner. Res. 2011;26:1989-96).

Dr. Glüer declared having no financial conflicts regarding the Eli Lilly–funded EuroGIOPs trial. Dr. Saag disclosed that he has received research grants from and serves as a paid consultant to Amgen, Eli Lilly, Merck, and Novartis.

Dr. Kenneth G. Saag noted that an anabolic agent such as teriparatide stimulates osteoblasts to promote new bone formation.

Source Courtesy University of Alabama

SAN DIEGO – Teriparatide has received a boost in status as a preferentially effective treatment for glucocorticoid-induced osteoporosis in the form of a second, confirmatory, randomized double-blind trial demonstrating the anabolic agent achieves substantially greater increases in bone mineral density compared to a bisphosphonate.

One of these studies also included fracture rates as a preplanned secondary end point; the trial showed a significant reduction in vertebral fractures with teriparatide (Forteo) as compared to alendronate (Fosamax).

These positive study findings are bolstered by a biologically plausible mechanism of benefit, observed Dr. Kenneth G. Saag. “Based upon the pathogenesis of glucocorticoid-induced osteoporosis [GIOP], we think that an anabolic agent makes some sense. It may be beneficial to stimulate osteoblasts to promote new bone formation,” said Dr. Saag, professor of medicine and epidemiology at the University of Alabama at Birmingham.

Steroids are known to have apoptosis-mediated deleterious effects on both osteocytes and osteoblasts that lead to decline in bone function and an abrupt increase in fracture risk independent of bone mineral density (BMD). Osteoclasts are also unfavorably impacted because of cross talk and the indirect effects of sex steroids, insulin-like growth factor, and a modest effect of secondary hyperparathyroidism mediated through altered calcium absorption. In addition, higher-dose steroids have adverse effects upon muscle that can independently lead to a higher fracture rate, he explained.

The Food and Drug Administration has approved alendronate, zoledronic acid (Reclast), risedronate (Actonel), and teriparatide (Forteo) for treatment of GIOP. More recently, raloxifene (Evista) has joined the ranks of agents shown to increase BMD in patients on long-term steroids; this came in the form of a double-blind, placebo-controlled, 12-month study (Ann. Rheum. Dis. 2011;70:778-84).

Subcutaneous daily teriparatide for up to 2 years also has the approval of the FDA for use in adults at high fracture risk because they are on sustained systemic steroid therapy.

There is no definitive study demonstrating that any of these agents actually prevents fractures in patients with GIOP.

However, data from a study in which Dr. Saag was lead investigator showed that teriparatide-treated patients had significantly fewer vertebral fractures than those assigned to alendronate. The study was a 36-month randomized, double-blind, clinical trial that assessed fracture rates as a preplanned secondary end point. The radiographic and clinical vertebral fracture rates in 169 alendronate-treated patients were 7.7% and 2.4%, respectively, compared with 1.7% and 0% in 173 teriparatide-treated patients (P = .007 and .037). No significant difference in nonvertebral fractures was found between the two treatment arms.

The primary study end point was the change in BMD from baseline. Here again teriparatide proved significantly more effective than the bisphosphonate, with a mean 11% increase at the lumbar spine, compared to 5.3% with alendronate.

Teriparatide-treated patients also had a 5.2% increase in BMD at the total hip and a 6.3% boost at the femoral neck, compared to 2.7% and 3.4%, respectively, with alendronate (Arthritis Rheum. 2009;60:3346-55).

Confirmation of teriparatide's superior BMD-building effect came from the EuroGIOPs trial presented by Dr. Claus C. Glüer at the ASBMR meeting.

EuroGIOPS was an 18-month, open-label, phase III clinical trial in which 92 men with GIOP were randomized to teriparatide or risedronate.

At 6 months the mean increase in lumbar spine BMD was 5.7% in the teriparatide group, compared with 3.3% in the risedronate arm.

At 18 months – the primary study end point – the teriparatide group averaged a 16.3% BMD increase over baseline, while the risedronate arm had a 3.8% rise.

Intriguingly, new clinical fractures occurred during 18 months of therapy in five patients on risedronate and none on teriparatide, a difference that came within a hair of statistical significance (P = .056).

Bone strength as formally measured in terms of anterior bending, axial compression, and axial torsion was also significantly greater in the teriparatide group, according to Dr. Glüer, who is professor of medical physics at the department of diagnostic radiology, University Hospital Schleswig-Holstein in Kiel, Germany.

The 2010 update of the American College of Rheumatology guidelines for the prevention and treatment of GIOP recommend bisphosphonates but not teriparatide for older adults at high risk of fracture who are taking less than 5 mg/day of prednisone for less than 1 month (Arthritis Care Res. 2010;62:1515-26).

The ACR guidelines recommend reserving use of teriparatide for high-risk patients – that is, those with a prevalent fracture or a World Health Organization Fracture Risk Assessment Tool (FRAX) score indicative of a greater than 20% 10-year risk of a major osteoporotic fracture – who are on at least 6 mg/day of prednisone for less than 1 month or on any dose of glucocorticoids for longer than 1 month.

Although Dr. Saag was a coauthor of the ACR guidelines, he was pleased to see a new commentary on the ACR guidelines published by the Professional Practice Committee of the ASBMR. The review recommends teriparatide or any of the bisphosphonates for high-risk patients, period.

Dr. Saag, who was not involved in the ASBMR review, recommended it as useful reading both for its areas of agreement with the ACR guidelines as well as for raising several patient scenarios in which the ASBMR committee believes the ACR recommendations either do not apply or might be improved upon (J. Bone Miner. Res. 2011;26:1989-96).

Dr. Glüer declared having no financial conflicts regarding the Eli Lilly–funded EuroGIOPs trial. Dr. Saag disclosed that he has received research grants from and serves as a paid consultant to Amgen, Eli Lilly, Merck, and Novartis.

Dr. Kenneth G. Saag noted that an anabolic agent such as teriparatide stimulates osteoblasts to promote new bone formation.

Source Courtesy University of Alabama

Major Finding: Denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo.

Data Source: Subgroup analysis in the original study of 7,808 postmenopausal women aged 60-80 years with osteoporosis who received every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements.

Disclosures: Dr. Cummings has been a consultant to Amgen Pharmaceuticals, which markets denosumab; to Merck, which markets alendronate; and to Eli Lilly and Company.

SAN FRANCISCO – The pivotal clinical trial of denosumab showed a 20% decrease in nonvertebral fractures compared with placebo treatment, but a new subgroup analysis shows the protective effect is significantly higher in patients with femoral neck osteoporosis.

The preplanned subgroup analysis of data from the FREEDOM trial found that denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo, Dr. Steven R. Cummings said.

The report of a 20% reduction in nonvertebral fractures in the overall trial for denosumab “underestimates its efficacy for those patients that we're most interested in treating with this drug – those with osteoporosis,” he said at the conference, sponsored by the University of California, San Francisco.

The analysis is one of several preplanned subgroup analyses being conducted, though this one is “the most interesting result for clinical care,” said Dr. Cummings, emeritus professor of medicine and epidemiology and biostatistics at the university.

The original FREEDOM study (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements. All subjects had bone mineral density T scores less than −2.5 but not less than −4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756-65).

The FREEDOM results were the basis of the Food and Drug Administration's approval of denosumab in June 2010.

Data for 2,343 patients who continued denosumab for another 2 years and 2,207 patients who switched from placebo to denosumab in an ongoing extension of the trial suggest that the incidence of nonvertebral fractures continues to decline in the first 5 years of denosumab use. The 5-year results have been submitted for publication, he said (“Denosumab's Bone Benefits Persist at 5 Years of Therapy,”

For nonvertebral fractures, the incidence decreased from 2.6% in the denosumab group in the first year of the FREEDOM trial to 2.1% in year 2 and 2.2% in year 3. Nonvertebral fractures were seen in 1.4% of patients in year 4 and 1.1% of patients in year 5, extension study data show. Similar rates were seen for vertebral fractures.

The extension study did not include a placebo comparison, so “we did a pretty rigorous estimate of what the rates would be if the placebo group had continued out to 5 years,” Dr. Cummings said. They estimated that nonvertebral or vertebral fracture rates would be 2.6% in the placebo group in years 4 and 5.

Major Finding: Denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo.

Data Source: Subgroup analysis in the original study of 7,808 postmenopausal women aged 60-80 years with osteoporosis who received every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements.

Disclosures: Dr. Cummings has been a consultant to Amgen Pharmaceuticals, which markets denosumab; to Merck, which markets alendronate; and to Eli Lilly and Company.

SAN FRANCISCO – The pivotal clinical trial of denosumab showed a 20% decrease in nonvertebral fractures compared with placebo treatment, but a new subgroup analysis shows the protective effect is significantly higher in patients with femoral neck osteoporosis.

The preplanned subgroup analysis of data from the FREEDOM trial found that denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo, Dr. Steven R. Cummings said.

The report of a 20% reduction in nonvertebral fractures in the overall trial for denosumab “underestimates its efficacy for those patients that we're most interested in treating with this drug – those with osteoporosis,” he said at the conference, sponsored by the University of California, San Francisco.

The analysis is one of several preplanned subgroup analyses being conducted, though this one is “the most interesting result for clinical care,” said Dr. Cummings, emeritus professor of medicine and epidemiology and biostatistics at the university.

The original FREEDOM study (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements. All subjects had bone mineral density T scores less than −2.5 but not less than −4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756-65).

The FREEDOM results were the basis of the Food and Drug Administration's approval of denosumab in June 2010.

Data for 2,343 patients who continued denosumab for another 2 years and 2,207 patients who switched from placebo to denosumab in an ongoing extension of the trial suggest that the incidence of nonvertebral fractures continues to decline in the first 5 years of denosumab use. The 5-year results have been submitted for publication, he said (“Denosumab's Bone Benefits Persist at 5 Years of Therapy,”

For nonvertebral fractures, the incidence decreased from 2.6% in the denosumab group in the first year of the FREEDOM trial to 2.1% in year 2 and 2.2% in year 3. Nonvertebral fractures were seen in 1.4% of patients in year 4 and 1.1% of patients in year 5, extension study data show. Similar rates were seen for vertebral fractures.

The extension study did not include a placebo comparison, so “we did a pretty rigorous estimate of what the rates would be if the placebo group had continued out to 5 years,” Dr. Cummings said. They estimated that nonvertebral or vertebral fracture rates would be 2.6% in the placebo group in years 4 and 5.

Major Finding: Denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo.

Data Source: Subgroup analysis in the original study of 7,808 postmenopausal women aged 60-80 years with osteoporosis who received every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements.

Disclosures: Dr. Cummings has been a consultant to Amgen Pharmaceuticals, which markets denosumab; to Merck, which markets alendronate; and to Eli Lilly and Company.

SAN FRANCISCO – The pivotal clinical trial of denosumab showed a 20% decrease in nonvertebral fractures compared with placebo treatment, but a new subgroup analysis shows the protective effect is significantly higher in patients with femoral neck osteoporosis.

The preplanned subgroup analysis of data from the FREEDOM trial found that denosumab decreased nonvertebral fractures by 35% in patients with a femoral neck bone mineral density T score of −2.5 or lower and by only 3% in patients with higher femoral neck T scores, compared with patients in those subgroups who received placebo, Dr. Steven R. Cummings said.

The report of a 20% reduction in nonvertebral fractures in the overall trial for denosumab “underestimates its efficacy for those patients that we're most interested in treating with this drug – those with osteoporosis,” he said at the conference, sponsored by the University of California, San Francisco.

The analysis is one of several preplanned subgroup analyses being conducted, though this one is “the most interesting result for clinical care,” said Dr. Cummings, emeritus professor of medicine and epidemiology and biostatistics at the university.

The original FREEDOM study (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) enrolled 7,808 postmenopausal women aged 60-80 years with osteoporosis to receive every 6 months either a subcutaneous injection of denosumab (60 mg) or placebo along with daily calcium and vitamin D supplements. All subjects had bone mineral density T scores less than −2.5 but not less than −4.0 at the lumbar spine or total hip. At 36 months, denosumab was associated with reductions of 68% in vertebral fracture and 40% in hip fracture (N. Engl. J. Med. 2009;361:756-65).

The FREEDOM results were the basis of the Food and Drug Administration's approval of denosumab in June 2010.

Data for 2,343 patients who continued denosumab for another 2 years and 2,207 patients who switched from placebo to denosumab in an ongoing extension of the trial suggest that the incidence of nonvertebral fractures continues to decline in the first 5 years of denosumab use. The 5-year results have been submitted for publication, he said (“Denosumab's Bone Benefits Persist at 5 Years of Therapy,”

For nonvertebral fractures, the incidence decreased from 2.6% in the denosumab group in the first year of the FREEDOM trial to 2.1% in year 2 and 2.2% in year 3. Nonvertebral fractures were seen in 1.4% of patients in year 4 and 1.1% of patients in year 5, extension study data show. Similar rates were seen for vertebral fractures.

The extension study did not include a placebo comparison, so “we did a pretty rigorous estimate of what the rates would be if the placebo group had continued out to 5 years,” Dr. Cummings said. They estimated that nonvertebral or vertebral fracture rates would be 2.6% in the placebo group in years 4 and 5.

SAN DIEGO – The more severe an anterior cruciate ligament injury, the more likely patients are to develop arthritis in the injured knee; structural changes might even be seen within 4 years of the trauma, a small study has shown.

In results presented at the World Congress on Osteoarthritis, patients who had had anterior cruciate ligament (ACL) reconstruction were four times more likely to have abnormal joint space narrowing by then if they also had a defect that extended more than halfway through their femoral cartilage (International Cartilage Repair Society grade III injury), a menisectomy, or both (odds ratio 4.11; 95% confidence interval 1.01-39.55, P = .05).

"These people were highly functioning; they were all athletic people. They had no symptoms of osteoarthritis," said lead investigator Timothy Tourville of the University of Vermont Center for Clinical and Translational Science in Burlington.

"Historically, most studies haven’t been able to demonstrate differences in [less than] 10 or 15 years. I think being able to pick them up at 4 years and identifying those who are at high risk for structural change is very important," rheumatologist David Hunter said in an interview.

"If, at the time of the injury, there is more substantive damage to either [the patient’s] cartilage or their meniscus, you are going to be more cautious about encouraging them to return to high physical activity and potentially redamaging their" knee, said Dr. Hunter, professor of medicine at the University of Sydney (Australia).

The 38 ACL patients in the study, about half women, were under 51 years of age and not obese. Their ACLs were reconstructed within a half-year of their injury, and none had gotten intra-articular injections. Other than their injury, they were in good health with no other joint problems. Baseline radiographs were compared with films at 3-4 years.

More than 60% (8/13) of those with grade III cartilage injuries had abnormal joint space narrowing at that point, compared with 28% (7/25) of those with no more than grade II injuries – defects extending less than halfway through their femoral cartilage – and intact menisci in both compartments.

"Abnormal" meant that the joint space difference between patients’ injured and uninjured knees fell outside the 95% confidence interval of bilateral differences measured in 32 matched controls.

The conference was sponsored by the Osteoarthritis Research Society International. Mr. Tourville and Dr. Hunter said they had no relevant financial disclosures. The National Institute of Arthritis and Musculoskeletal and Skin Diseases supported the work.

SAN DIEGO – The more severe an anterior cruciate ligament injury, the more likely patients are to develop arthritis in the injured knee; structural changes might even be seen within 4 years of the trauma, a small study has shown.

In results presented at the World Congress on Osteoarthritis, patients who had had anterior cruciate ligament (ACL) reconstruction were four times more likely to have abnormal joint space narrowing by then if they also had a defect that extended more than halfway through their femoral cartilage (International Cartilage Repair Society grade III injury), a menisectomy, or both (odds ratio 4.11; 95% confidence interval 1.01-39.55, P = .05).

"These people were highly functioning; they were all athletic people. They had no symptoms of osteoarthritis," said lead investigator Timothy Tourville of the University of Vermont Center for Clinical and Translational Science in Burlington.

"Historically, most studies haven’t been able to demonstrate differences in [less than] 10 or 15 years. I think being able to pick them up at 4 years and identifying those who are at high risk for structural change is very important," rheumatologist David Hunter said in an interview.

"If, at the time of the injury, there is more substantive damage to either [the patient’s] cartilage or their meniscus, you are going to be more cautious about encouraging them to return to high physical activity and potentially redamaging their" knee, said Dr. Hunter, professor of medicine at the University of Sydney (Australia).

The 38 ACL patients in the study, about half women, were under 51 years of age and not obese. Their ACLs were reconstructed within a half-year of their injury, and none had gotten intra-articular injections. Other than their injury, they were in good health with no other joint problems. Baseline radiographs were compared with films at 3-4 years.

More than 60% (8/13) of those with grade III cartilage injuries had abnormal joint space narrowing at that point, compared with 28% (7/25) of those with no more than grade II injuries – defects extending less than halfway through their femoral cartilage – and intact menisci in both compartments.

"Abnormal" meant that the joint space difference between patients’ injured and uninjured knees fell outside the 95% confidence interval of bilateral differences measured in 32 matched controls.

The conference was sponsored by the Osteoarthritis Research Society International. Mr. Tourville and Dr. Hunter said they had no relevant financial disclosures. The National Institute of Arthritis and Musculoskeletal and Skin Diseases supported the work.

SAN DIEGO – The more severe an anterior cruciate ligament injury, the more likely patients are to develop arthritis in the injured knee; structural changes might even be seen within 4 years of the trauma, a small study has shown.

In results presented at the World Congress on Osteoarthritis, patients who had had anterior cruciate ligament (ACL) reconstruction were four times more likely to have abnormal joint space narrowing by then if they also had a defect that extended more than halfway through their femoral cartilage (International Cartilage Repair Society grade III injury), a menisectomy, or both (odds ratio 4.11; 95% confidence interval 1.01-39.55, P = .05).

"These people were highly functioning; they were all athletic people. They had no symptoms of osteoarthritis," said lead investigator Timothy Tourville of the University of Vermont Center for Clinical and Translational Science in Burlington.

"Historically, most studies haven’t been able to demonstrate differences in [less than] 10 or 15 years. I think being able to pick them up at 4 years and identifying those who are at high risk for structural change is very important," rheumatologist David Hunter said in an interview.

"If, at the time of the injury, there is more substantive damage to either [the patient’s] cartilage or their meniscus, you are going to be more cautious about encouraging them to return to high physical activity and potentially redamaging their" knee, said Dr. Hunter, professor of medicine at the University of Sydney (Australia).

The 38 ACL patients in the study, about half women, were under 51 years of age and not obese. Their ACLs were reconstructed within a half-year of their injury, and none had gotten intra-articular injections. Other than their injury, they were in good health with no other joint problems. Baseline radiographs were compared with films at 3-4 years.

More than 60% (8/13) of those with grade III cartilage injuries had abnormal joint space narrowing at that point, compared with 28% (7/25) of those with no more than grade II injuries – defects extending less than halfway through their femoral cartilage – and intact menisci in both compartments.

"Abnormal" meant that the joint space difference between patients’ injured and uninjured knees fell outside the 95% confidence interval of bilateral differences measured in 32 matched controls.

The conference was sponsored by the Osteoarthritis Research Society International. Mr. Tourville and Dr. Hunter said they had no relevant financial disclosures. The National Institute of Arthritis and Musculoskeletal and Skin Diseases supported the work.

SAN DIEGO – Angiotensin-converting enzyme inhibitor therapy may reduce the risk of age-related bone loss in elderly men.

A retrospective analysis of longitudinal data from the prospective Health ABC (Dynamics of Health, Aging and Body Composition Study) found that femoral neck bone mineral density was significantly greater in elderly men on an ACE inhibitor for 5 or more years for treatment of hypertension than in those who were not on long-term ACE inhibitor therapy, Dr. Nahid Rianon reported at the annual meeting of the American Society for Bone and Mineral Research.

This secondary analysis of Health ABC involved 583 men with a mean age of 83 years. At 10-year follow-up, femoral neck bone mineral density was 0.04 g/cm² greater in the 137 subjects on an ACE inhibitor for at least 5 years than in men not on long-term therapy with a drug in this class.

Of note, the same magnitude of improvement in femoral neck bone mineral density was seen after just 5 years of ACE inhibitor therapy. In other words, no further divergence in bone mineral density occurred during years 5-10.

These study findings warrant confirmation in a prospective clinical trial featuring analysis of bone markers, which wasn’t done in Health ABC. Osteoporosis and hypertension are two major age-related chronic diseases that at present are managed separately using different classes of drugs. If ACE inhibitors can be shown to be beneficial in both of these extremely common diseases, management would be considerably simplified, observed Dr. Rianon of the University of Texas, Houston.

The finding that long-term ACE inhibitor therapy appears to prevent age-related bone loss in older men has mechanistic plausibility, the physician continued. These drugs inhibit production of angiotensin II, a hormone that affects bone by binding to the angiotensin-1 and angiotensin-2 receptors expressed in osteoblasts, among other sites. And angiotensin-1 and angiotensin-2 expression appears to promote receptor-activated nuclear factor–kappaB ligand activity, which enhances bone loss.

Health ABC is sponsored by the National Institute on Aging. Dr. Rianon declared having no financial conflicts.

SAN DIEGO – Angiotensin-converting enzyme inhibitor therapy may reduce the risk of age-related bone loss in elderly men.

A retrospective analysis of longitudinal data from the prospective Health ABC (Dynamics of Health, Aging and Body Composition Study) found that femoral neck bone mineral density was significantly greater in elderly men on an ACE inhibitor for 5 or more years for treatment of hypertension than in those who were not on long-term ACE inhibitor therapy, Dr. Nahid Rianon reported at the annual meeting of the American Society for Bone and Mineral Research.

This secondary analysis of Health ABC involved 583 men with a mean age of 83 years. At 10-year follow-up, femoral neck bone mineral density was 0.04 g/cm² greater in the 137 subjects on an ACE inhibitor for at least 5 years than in men not on long-term therapy with a drug in this class.

Of note, the same magnitude of improvement in femoral neck bone mineral density was seen after just 5 years of ACE inhibitor therapy. In other words, no further divergence in bone mineral density occurred during years 5-10.

These study findings warrant confirmation in a prospective clinical trial featuring analysis of bone markers, which wasn’t done in Health ABC. Osteoporosis and hypertension are two major age-related chronic diseases that at present are managed separately using different classes of drugs. If ACE inhibitors can be shown to be beneficial in both of these extremely common diseases, management would be considerably simplified, observed Dr. Rianon of the University of Texas, Houston.

The finding that long-term ACE inhibitor therapy appears to prevent age-related bone loss in older men has mechanistic plausibility, the physician continued. These drugs inhibit production of angiotensin II, a hormone that affects bone by binding to the angiotensin-1 and angiotensin-2 receptors expressed in osteoblasts, among other sites. And angiotensin-1 and angiotensin-2 expression appears to promote receptor-activated nuclear factor–kappaB ligand activity, which enhances bone loss.

Health ABC is sponsored by the National Institute on Aging. Dr. Rianon declared having no financial conflicts.

SAN DIEGO – Angiotensin-converting enzyme inhibitor therapy may reduce the risk of age-related bone loss in elderly men.

A retrospective analysis of longitudinal data from the prospective Health ABC (Dynamics of Health, Aging and Body Composition Study) found that femoral neck bone mineral density was significantly greater in elderly men on an ACE inhibitor for 5 or more years for treatment of hypertension than in those who were not on long-term ACE inhibitor therapy, Dr. Nahid Rianon reported at the annual meeting of the American Society for Bone and Mineral Research.

This secondary analysis of Health ABC involved 583 men with a mean age of 83 years. At 10-year follow-up, femoral neck bone mineral density was 0.04 g/cm² greater in the 137 subjects on an ACE inhibitor for at least 5 years than in men not on long-term therapy with a drug in this class.

Of note, the same magnitude of improvement in femoral neck bone mineral density was seen after just 5 years of ACE inhibitor therapy. In other words, no further divergence in bone mineral density occurred during years 5-10.

These study findings warrant confirmation in a prospective clinical trial featuring analysis of bone markers, which wasn’t done in Health ABC. Osteoporosis and hypertension are two major age-related chronic diseases that at present are managed separately using different classes of drugs. If ACE inhibitors can be shown to be beneficial in both of these extremely common diseases, management would be considerably simplified, observed Dr. Rianon of the University of Texas, Houston.

The finding that long-term ACE inhibitor therapy appears to prevent age-related bone loss in older men has mechanistic plausibility, the physician continued. These drugs inhibit production of angiotensin II, a hormone that affects bone by binding to the angiotensin-1 and angiotensin-2 receptors expressed in osteoblasts, among other sites. And angiotensin-1 and angiotensin-2 expression appears to promote receptor-activated nuclear factor–kappaB ligand activity, which enhances bone loss.

Health ABC is sponsored by the National Institute on Aging. Dr. Rianon declared having no financial conflicts.