Osteoarthritis

SAN ANTONIO — Twice-yearly intravenous zoledronic acid started simultaneously with aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer shows promise as a means of preventing bone loss and even building bone, according to the 2-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST).

Z-FAST is an ongoing open-label multicenter randomized trial involving 600 U.S. and Canadian women receiving up to 5 years of adjuvant letrozole (Femara) as part of the treatment of hormone receptor-positive early breast cancer. Participants were randomized to up-front 15-minute infusions of 4 mg of zoledronic acid every 6 months or to the delayed start of bisphosphonate until after a clinical fracture occurred or a patient's bone mineral density (BMD) T score dropped to below 2. Through 24 months, 12.7% of patients in the delayed group had initiated zoledronic acid, Dr. Adam M. Brufsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Z-FAST was designed to determine whether up-front zoledronic acid is the superior strategy for prevention of aromatase inhibitor-associated bone loss and fractures. The recently published 1-year Z-FAST results (J. Clin. Oncol. 2006 Dec. 11 [Epubdoi 10.1200/JCO.2005.05.3744]) showed up-front therapy protected against bone loss while the delayed strategy did not.

At 2 years, the gap in efficacy has widened. The mean increase in BMD at the lumbar spine was 3.1% with up-front zoledronic acid, compared with a mean 2.9% decline with delayed therapy. The mean increase in total hip BMD was 1.4% with up-front therapy, vs. a 3.2% drop with delayed therapy. Markers of bone turnover were continuously suppressed in the up-front therapy arm over 24 months, according to Dr. Brufsky of the University of Pittsburgh.

The incidence of clinical fractures through 24 months was 4.3% in the up-front therapy group and 4.0% in the delayed treatment arm. Two cases of renal impairment have occurred in the up-front therapy group, both believed related to zoledronic acid. No cases of osteonecrosis of the jaw have occurred in the 600-patient study.

Dr. Brufsky is a consultant to and member of the speakers' bureau for Z-FAST sponsor Novartis Pharmaceuticals.

SAN ANTONIO — Twice-yearly intravenous zoledronic acid started simultaneously with aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer shows promise as a means of preventing bone loss and even building bone, according to the 2-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST).

Z-FAST is an ongoing open-label multicenter randomized trial involving 600 U.S. and Canadian women receiving up to 5 years of adjuvant letrozole (Femara) as part of the treatment of hormone receptor-positive early breast cancer. Participants were randomized to up-front 15-minute infusions of 4 mg of zoledronic acid every 6 months or to the delayed start of bisphosphonate until after a clinical fracture occurred or a patient's bone mineral density (BMD) T score dropped to below 2. Through 24 months, 12.7% of patients in the delayed group had initiated zoledronic acid, Dr. Adam M. Brufsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Z-FAST was designed to determine whether up-front zoledronic acid is the superior strategy for prevention of aromatase inhibitor-associated bone loss and fractures. The recently published 1-year Z-FAST results (J. Clin. Oncol. 2006 Dec. 11 [Epubdoi 10.1200/JCO.2005.05.3744]) showed up-front therapy protected against bone loss while the delayed strategy did not.

At 2 years, the gap in efficacy has widened. The mean increase in BMD at the lumbar spine was 3.1% with up-front zoledronic acid, compared with a mean 2.9% decline with delayed therapy. The mean increase in total hip BMD was 1.4% with up-front therapy, vs. a 3.2% drop with delayed therapy. Markers of bone turnover were continuously suppressed in the up-front therapy arm over 24 months, according to Dr. Brufsky of the University of Pittsburgh.

The incidence of clinical fractures through 24 months was 4.3% in the up-front therapy group and 4.0% in the delayed treatment arm. Two cases of renal impairment have occurred in the up-front therapy group, both believed related to zoledronic acid. No cases of osteonecrosis of the jaw have occurred in the 600-patient study.

Dr. Brufsky is a consultant to and member of the speakers' bureau for Z-FAST sponsor Novartis Pharmaceuticals.

SAN ANTONIO — Twice-yearly intravenous zoledronic acid started simultaneously with aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive early-stage breast cancer shows promise as a means of preventing bone loss and even building bone, according to the 2-year results of the Zometa-Femara Adjuvant Synergy Trial (Z-FAST).

Z-FAST is an ongoing open-label multicenter randomized trial involving 600 U.S. and Canadian women receiving up to 5 years of adjuvant letrozole (Femara) as part of the treatment of hormone receptor-positive early breast cancer. Participants were randomized to up-front 15-minute infusions of 4 mg of zoledronic acid every 6 months or to the delayed start of bisphosphonate until after a clinical fracture occurred or a patient's bone mineral density (BMD) T score dropped to below 2. Through 24 months, 12.7% of patients in the delayed group had initiated zoledronic acid, Dr. Adam M. Brufsky reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Z-FAST was designed to determine whether up-front zoledronic acid is the superior strategy for prevention of aromatase inhibitor-associated bone loss and fractures. The recently published 1-year Z-FAST results (J. Clin. Oncol. 2006 Dec. 11 [Epubdoi 10.1200/JCO.2005.05.3744]) showed up-front therapy protected against bone loss while the delayed strategy did not.

At 2 years, the gap in efficacy has widened. The mean increase in BMD at the lumbar spine was 3.1% with up-front zoledronic acid, compared with a mean 2.9% decline with delayed therapy. The mean increase in total hip BMD was 1.4% with up-front therapy, vs. a 3.2% drop with delayed therapy. Markers of bone turnover were continuously suppressed in the up-front therapy arm over 24 months, according to Dr. Brufsky of the University of Pittsburgh.

The incidence of clinical fractures through 24 months was 4.3% in the up-front therapy group and 4.0% in the delayed treatment arm. Two cases of renal impairment have occurred in the up-front therapy group, both believed related to zoledronic acid. No cases of osteonecrosis of the jaw have occurred in the 600-patient study.

Dr. Brufsky is a consultant to and member of the speakers' bureau for Z-FAST sponsor Novartis Pharmaceuticals.

VERONA, ITALY — Contrary to conventional wisdom, obese patients may not be protected against osteoporosis and could present with significant bone loss, new data show.

In a study of 233 morbidly obese patients, 34% showed a significant decrease in bone mineral density at the lumbar spine with a median T score of −1.98 (range −1.1 to −4.2), Dr. Carlo Lubrano and his colleagues reported in a poster at a joint meeting of the Italian Association of Clinical Endocrinologists and the American Association of Clinical Endocrinologists.

Low bone mass is defined as a bone density at the spine or hip between 1.0 and 2.4 standard deviations below the average for healthy young adults, which translates to a T score of −1 to −2.5, according to the World Health Organization. Bone density 2.5 standard deviations or more below the young adult mean is categorized as osteoporosis.

The 195 women and 38 men in the study had an average body mass index of 37 kg/m

Overall, 31.5% of the women showed a median BMD of 0.971 g/cm

Few data are available on potential skeletal modifications in patients affected by severe obesity. It had been thought that, although obese patients are often affected by hypertension, dyslipidemia, impaired glucose metabolism, and an increase in cardiovascular diseases, obesity might protect the skeleton against osteoporosis. Recent evidence suggests that obesity may actually weaken the skeleton and increase the risk of fractures.

Given their findings, the authors concluded that a “specific and careful characterization of skeletal metabolism might be useful in both female and male obese subjects.”

VERONA, ITALY — Contrary to conventional wisdom, obese patients may not be protected against osteoporosis and could present with significant bone loss, new data show.

In a study of 233 morbidly obese patients, 34% showed a significant decrease in bone mineral density at the lumbar spine with a median T score of −1.98 (range −1.1 to −4.2), Dr. Carlo Lubrano and his colleagues reported in a poster at a joint meeting of the Italian Association of Clinical Endocrinologists and the American Association of Clinical Endocrinologists.

Low bone mass is defined as a bone density at the spine or hip between 1.0 and 2.4 standard deviations below the average for healthy young adults, which translates to a T score of −1 to −2.5, according to the World Health Organization. Bone density 2.5 standard deviations or more below the young adult mean is categorized as osteoporosis.

The 195 women and 38 men in the study had an average body mass index of 37 kg/m

Overall, 31.5% of the women showed a median BMD of 0.971 g/cm

Few data are available on potential skeletal modifications in patients affected by severe obesity. It had been thought that, although obese patients are often affected by hypertension, dyslipidemia, impaired glucose metabolism, and an increase in cardiovascular diseases, obesity might protect the skeleton against osteoporosis. Recent evidence suggests that obesity may actually weaken the skeleton and increase the risk of fractures.

Given their findings, the authors concluded that a “specific and careful characterization of skeletal metabolism might be useful in both female and male obese subjects.”

VERONA, ITALY — Contrary to conventional wisdom, obese patients may not be protected against osteoporosis and could present with significant bone loss, new data show.

In a study of 233 morbidly obese patients, 34% showed a significant decrease in bone mineral density at the lumbar spine with a median T score of −1.98 (range −1.1 to −4.2), Dr. Carlo Lubrano and his colleagues reported in a poster at a joint meeting of the Italian Association of Clinical Endocrinologists and the American Association of Clinical Endocrinologists.

Low bone mass is defined as a bone density at the spine or hip between 1.0 and 2.4 standard deviations below the average for healthy young adults, which translates to a T score of −1 to −2.5, according to the World Health Organization. Bone density 2.5 standard deviations or more below the young adult mean is categorized as osteoporosis.

The 195 women and 38 men in the study had an average body mass index of 37 kg/m

Overall, 31.5% of the women showed a median BMD of 0.971 g/cm

Few data are available on potential skeletal modifications in patients affected by severe obesity. It had been thought that, although obese patients are often affected by hypertension, dyslipidemia, impaired glucose metabolism, and an increase in cardiovascular diseases, obesity might protect the skeleton against osteoporosis. Recent evidence suggests that obesity may actually weaken the skeleton and increase the risk of fractures.

Given their findings, the authors concluded that a “specific and careful characterization of skeletal metabolism might be useful in both female and male obese subjects.”

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both patients who take these frequently prescribed drugs and physicians.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine₂ receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid-suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls.

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both patients who take these frequently prescribed drugs and physicians.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine₂ receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid-suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls.

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both patients who take these frequently prescribed drugs and physicians.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine₂ receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid-suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls.

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Reduced use of benzodiazepines in elderly patients does not necessarily result in a lower incidence of hip fracture, according to a study by Anita Wagner, Pharm.D., of the department of ambulatory care and prevention at Harvard Medical School, Boston, and her colleagues.

The researchers found no significant difference in the incidence of hip fracture over a 3-year period between elderly Medicaid recipients in New York, where benzodiazepine use decreased sharply during the study period, and in New Jersey, where benzodiazepine use remained constant.

“Benzodiazepines may not actually be associated with hip fractures, or at least not to the extent reported in some studies,” Dr. Wagner and her colleagues wrote (Ann. Intern. Med. 2007;146:96–103).

The Prescription Drug Improvement and Modernization Act that went into effect in January 2006 further restricted benzodiazepine prescription coverage for Medicare recipients. Federal policy makers may have expected that reduced benzodiazepine access would decrease hip fracture risk and thereby improve quality of life in the elderly.

“According to our analyses, this expectation may not be justified,” Dr. Wagner and her associates concluded.

Earlier studies had suggested that benzodiazepine use might increase the risk of hip fracture in elderly patients, with postural imbalance associated with benzodiazepine use possibly leading to more falls and hip fractures in a population already at risk for hip fracture. But studies seeking to document a direct link have yielded conflicting results.

Since 1989, physicians in New York have been required to use serially numbered, triplicate forms for benzodiazepine prescriptions, with the third copy to be forwarded by the pharmacy to the state health authorities.

The study compared the risk of hip fractures in 1988 cohorts of 51,529 elderly Medicaid recipients in New York and 42,029 in New Jersey, where the prescription policy was unchanged.

In New York, the change in prescription policy led to an abrupt decline in benzodiazepine use, decreasing from about 40% of Medicaid enrollees each month in the 12-month period before the policy change to about 15% during the 21 months after the policy change. Benzodiazepine use among New Jersey Medicaid enrollees did not change significantly.

In New York, a total of 199 hip fractures occurred in female benzodiazepine recipients over the 33-month study period, with an increase in hazard rate from 53 per 100,000 enrollees before the policy change to 72 per 100,000 enrollees after the policy change.

In New Jersey, 135 hip fractures occurred in female benzodiazepine recipients in the study period, with a similar increase in hazard rate from 42 per 100,000 enrollees to 58 per 100,000 enrollees. A total of 30 hip fractures in male benzodiazepine recipients in New York occurred over the study period, with the hazard rate increasing from 38 per 100,000 enrollees before the policy change to 54 per 100,000 enrollees after the policy change. New Jersey results were similar, with a total of 27 hip fractures among male benzodiazepine recipients and an increase in hazard rate from 48 per 100,000 enrollees before the policy change in New York to 52 per 100,000 enrollees. In each case, hazard rates among benzodiazepine nonrecipients were similar.

No evidence suggests that the study results were skewed by disproportionate reductions in benzodiazepine use among different patient subgroups. After the policy change, there was no significant increase in the prevalence of higher-dose benzodiazepine prescriptions, and the increase in nonbenzodiazepine sedatives was modest.

The most likely explanation for the lack of decrease in hip fractures following decreased benzodiazepine use is simply that benzodiazepine use does not increase the risk of hip fracture in the elderly, Dr. Wagner and her colleagues wrote.

Reduced use of benzodiazepines in elderly patients does not necessarily result in a lower incidence of hip fracture, according to a study by Anita Wagner, Pharm.D., of the department of ambulatory care and prevention at Harvard Medical School, Boston, and her colleagues.

The researchers found no significant difference in the incidence of hip fracture over a 3-year period between elderly Medicaid recipients in New York, where benzodiazepine use decreased sharply during the study period, and in New Jersey, where benzodiazepine use remained constant.

“Benzodiazepines may not actually be associated with hip fractures, or at least not to the extent reported in some studies,” Dr. Wagner and her colleagues wrote (Ann. Intern. Med. 2007;146:96–103).

The Prescription Drug Improvement and Modernization Act that went into effect in January 2006 further restricted benzodiazepine prescription coverage for Medicare recipients. Federal policy makers may have expected that reduced benzodiazepine access would decrease hip fracture risk and thereby improve quality of life in the elderly.

“According to our analyses, this expectation may not be justified,” Dr. Wagner and her associates concluded.

Earlier studies had suggested that benzodiazepine use might increase the risk of hip fracture in elderly patients, with postural imbalance associated with benzodiazepine use possibly leading to more falls and hip fractures in a population already at risk for hip fracture. But studies seeking to document a direct link have yielded conflicting results.

Since 1989, physicians in New York have been required to use serially numbered, triplicate forms for benzodiazepine prescriptions, with the third copy to be forwarded by the pharmacy to the state health authorities.

The study compared the risk of hip fractures in 1988 cohorts of 51,529 elderly Medicaid recipients in New York and 42,029 in New Jersey, where the prescription policy was unchanged.

In New York, the change in prescription policy led to an abrupt decline in benzodiazepine use, decreasing from about 40% of Medicaid enrollees each month in the 12-month period before the policy change to about 15% during the 21 months after the policy change. Benzodiazepine use among New Jersey Medicaid enrollees did not change significantly.

In New York, a total of 199 hip fractures occurred in female benzodiazepine recipients over the 33-month study period, with an increase in hazard rate from 53 per 100,000 enrollees before the policy change to 72 per 100,000 enrollees after the policy change.

In New Jersey, 135 hip fractures occurred in female benzodiazepine recipients in the study period, with a similar increase in hazard rate from 42 per 100,000 enrollees to 58 per 100,000 enrollees. A total of 30 hip fractures in male benzodiazepine recipients in New York occurred over the study period, with the hazard rate increasing from 38 per 100,000 enrollees before the policy change to 54 per 100,000 enrollees after the policy change. New Jersey results were similar, with a total of 27 hip fractures among male benzodiazepine recipients and an increase in hazard rate from 48 per 100,000 enrollees before the policy change in New York to 52 per 100,000 enrollees. In each case, hazard rates among benzodiazepine nonrecipients were similar.

No evidence suggests that the study results were skewed by disproportionate reductions in benzodiazepine use among different patient subgroups. After the policy change, there was no significant increase in the prevalence of higher-dose benzodiazepine prescriptions, and the increase in nonbenzodiazepine sedatives was modest.

The most likely explanation for the lack of decrease in hip fractures following decreased benzodiazepine use is simply that benzodiazepine use does not increase the risk of hip fracture in the elderly, Dr. Wagner and her colleagues wrote.

Reduced use of benzodiazepines in elderly patients does not necessarily result in a lower incidence of hip fracture, according to a study by Anita Wagner, Pharm.D., of the department of ambulatory care and prevention at Harvard Medical School, Boston, and her colleagues.

The researchers found no significant difference in the incidence of hip fracture over a 3-year period between elderly Medicaid recipients in New York, where benzodiazepine use decreased sharply during the study period, and in New Jersey, where benzodiazepine use remained constant.

“Benzodiazepines may not actually be associated with hip fractures, or at least not to the extent reported in some studies,” Dr. Wagner and her colleagues wrote (Ann. Intern. Med. 2007;146:96–103).

The Prescription Drug Improvement and Modernization Act that went into effect in January 2006 further restricted benzodiazepine prescription coverage for Medicare recipients. Federal policy makers may have expected that reduced benzodiazepine access would decrease hip fracture risk and thereby improve quality of life in the elderly.

“According to our analyses, this expectation may not be justified,” Dr. Wagner and her associates concluded.

Earlier studies had suggested that benzodiazepine use might increase the risk of hip fracture in elderly patients, with postural imbalance associated with benzodiazepine use possibly leading to more falls and hip fractures in a population already at risk for hip fracture. But studies seeking to document a direct link have yielded conflicting results.

Since 1989, physicians in New York have been required to use serially numbered, triplicate forms for benzodiazepine prescriptions, with the third copy to be forwarded by the pharmacy to the state health authorities.

The study compared the risk of hip fractures in 1988 cohorts of 51,529 elderly Medicaid recipients in New York and 42,029 in New Jersey, where the prescription policy was unchanged.

In New York, the change in prescription policy led to an abrupt decline in benzodiazepine use, decreasing from about 40% of Medicaid enrollees each month in the 12-month period before the policy change to about 15% during the 21 months after the policy change. Benzodiazepine use among New Jersey Medicaid enrollees did not change significantly.

In New York, a total of 199 hip fractures occurred in female benzodiazepine recipients over the 33-month study period, with an increase in hazard rate from 53 per 100,000 enrollees before the policy change to 72 per 100,000 enrollees after the policy change.

In New Jersey, 135 hip fractures occurred in female benzodiazepine recipients in the study period, with a similar increase in hazard rate from 42 per 100,000 enrollees to 58 per 100,000 enrollees. A total of 30 hip fractures in male benzodiazepine recipients in New York occurred over the study period, with the hazard rate increasing from 38 per 100,000 enrollees before the policy change to 54 per 100,000 enrollees after the policy change. New Jersey results were similar, with a total of 27 hip fractures among male benzodiazepine recipients and an increase in hazard rate from 48 per 100,000 enrollees before the policy change in New York to 52 per 100,000 enrollees. In each case, hazard rates among benzodiazepine nonrecipients were similar.

No evidence suggests that the study results were skewed by disproportionate reductions in benzodiazepine use among different patient subgroups. After the policy change, there was no significant increase in the prevalence of higher-dose benzodiazepine prescriptions, and the increase in nonbenzodiazepine sedatives was modest.

The most likely explanation for the lack of decrease in hip fractures following decreased benzodiazepine use is simply that benzodiazepine use does not increase the risk of hip fracture in the elderly, Dr. Wagner and her colleagues wrote.

PHILADELPHIA — Weekly parathyroid hormone increases bone mineral density and bone formation biomarkers, but only slightly, Dennis M. Black, Ph.D., reported at the annual meeting of the American Society for Bone and Mineral Research.

Spine bone mineral density (BMD) increased 2.1% in women on parathyroid hormone (PTH) at the end of 1 year, compared with women receiving no treatment, a significant finding. Trabecular spine volumetric BMD assessed with quantitative CT increased 3.8% in women in the treatment group, compared with those in the control group, though this result was not significant, Dr. Black said. There also were trends toward increases in trabecular number and cortical thickness, though these were not statistically significant.

In the PTH Once Weekly Research (POWR) study, 50 women were randomized evenly to treatment with PTH (1–84) at a dosage of 100 mcg daily for 1 month followed by 11 months of once weekly PTH (also 100 mcg) or no treatment. All women also received 500 mg calcium and 400 IU vitamin D per day, reported Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco. Women had to be postmenopausal and aged between 45 and 70 years, with minimal previous use of bisphosphonates. They also had to have a femoral neck BMD T score between −1 and −2 and a spine BMD T score greater than −2.5.

The primary end point was spine BMD measured by dual-energy x-ray absorptiometry (DXA). Secondary end points included BMD at the hip, trabecular, and cortical bone measured by quantitative CT at the spine and hip and bone biomarkers. Based on injection diaries, 94% of the women were found to have at least an 80% compliance with the injection regimen, he said.

Bone formation during daily treatment with PTH, as measured by procollagen type 1 N-propeptide (P1NP) levels, increased roughly 100% compared with untreated women. However, levels slowly decreased during weekly injections, remaining 15% greater than for untreated women at 12 months. There were no significant changes in resorption markers in either group.

He compared the results of this pilot study with those for daily PTH treatment at 12 months from the Parathyroid Hormone and Alendronate (PaTH) study (N. Engl. J. Med. 2005;353:555–65).

Once-weekly PTH following daily PTH for 1 month significantly increased spine BMD. However, compared with daily PTH in the PaTh study, “there was no significant increase in trabecular BMD, a small increase in DXA spine BMD, a smaller increase in bone formation markers, and generally a smaller anabolic response,” he said.

Once weekly PTH may not be frequent enough. A longer loading period may be necessary, he noted. In terms of adverse events, there was one case of chest pain in the placebo group, and there were four mild cases of hypercalcemia in the PTH group.

Dr. Black disclosed that he has significant financial relationships with Novartis, Merck & Co., Hoffmann-La Roche Inc., and GlaxoSmithKline.

PHILADELPHIA — Weekly parathyroid hormone increases bone mineral density and bone formation biomarkers, but only slightly, Dennis M. Black, Ph.D., reported at the annual meeting of the American Society for Bone and Mineral Research.

Spine bone mineral density (BMD) increased 2.1% in women on parathyroid hormone (PTH) at the end of 1 year, compared with women receiving no treatment, a significant finding. Trabecular spine volumetric BMD assessed with quantitative CT increased 3.8% in women in the treatment group, compared with those in the control group, though this result was not significant, Dr. Black said. There also were trends toward increases in trabecular number and cortical thickness, though these were not statistically significant.

In the PTH Once Weekly Research (POWR) study, 50 women were randomized evenly to treatment with PTH (1–84) at a dosage of 100 mcg daily for 1 month followed by 11 months of once weekly PTH (also 100 mcg) or no treatment. All women also received 500 mg calcium and 400 IU vitamin D per day, reported Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco. Women had to be postmenopausal and aged between 45 and 70 years, with minimal previous use of bisphosphonates. They also had to have a femoral neck BMD T score between −1 and −2 and a spine BMD T score greater than −2.5.

The primary end point was spine BMD measured by dual-energy x-ray absorptiometry (DXA). Secondary end points included BMD at the hip, trabecular, and cortical bone measured by quantitative CT at the spine and hip and bone biomarkers. Based on injection diaries, 94% of the women were found to have at least an 80% compliance with the injection regimen, he said.

Bone formation during daily treatment with PTH, as measured by procollagen type 1 N-propeptide (P1NP) levels, increased roughly 100% compared with untreated women. However, levels slowly decreased during weekly injections, remaining 15% greater than for untreated women at 12 months. There were no significant changes in resorption markers in either group.

He compared the results of this pilot study with those for daily PTH treatment at 12 months from the Parathyroid Hormone and Alendronate (PaTH) study (N. Engl. J. Med. 2005;353:555–65).

Once-weekly PTH following daily PTH for 1 month significantly increased spine BMD. However, compared with daily PTH in the PaTh study, “there was no significant increase in trabecular BMD, a small increase in DXA spine BMD, a smaller increase in bone formation markers, and generally a smaller anabolic response,” he said.

Once weekly PTH may not be frequent enough. A longer loading period may be necessary, he noted. In terms of adverse events, there was one case of chest pain in the placebo group, and there were four mild cases of hypercalcemia in the PTH group.

Dr. Black disclosed that he has significant financial relationships with Novartis, Merck & Co., Hoffmann-La Roche Inc., and GlaxoSmithKline.

PHILADELPHIA — Weekly parathyroid hormone increases bone mineral density and bone formation biomarkers, but only slightly, Dennis M. Black, Ph.D., reported at the annual meeting of the American Society for Bone and Mineral Research.

Spine bone mineral density (BMD) increased 2.1% in women on parathyroid hormone (PTH) at the end of 1 year, compared with women receiving no treatment, a significant finding. Trabecular spine volumetric BMD assessed with quantitative CT increased 3.8% in women in the treatment group, compared with those in the control group, though this result was not significant, Dr. Black said. There also were trends toward increases in trabecular number and cortical thickness, though these were not statistically significant.

In the PTH Once Weekly Research (POWR) study, 50 women were randomized evenly to treatment with PTH (1–84) at a dosage of 100 mcg daily for 1 month followed by 11 months of once weekly PTH (also 100 mcg) or no treatment. All women also received 500 mg calcium and 400 IU vitamin D per day, reported Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco. Women had to be postmenopausal and aged between 45 and 70 years, with minimal previous use of bisphosphonates. They also had to have a femoral neck BMD T score between −1 and −2 and a spine BMD T score greater than −2.5.

The primary end point was spine BMD measured by dual-energy x-ray absorptiometry (DXA). Secondary end points included BMD at the hip, trabecular, and cortical bone measured by quantitative CT at the spine and hip and bone biomarkers. Based on injection diaries, 94% of the women were found to have at least an 80% compliance with the injection regimen, he said.

Bone formation during daily treatment with PTH, as measured by procollagen type 1 N-propeptide (P1NP) levels, increased roughly 100% compared with untreated women. However, levels slowly decreased during weekly injections, remaining 15% greater than for untreated women at 12 months. There were no significant changes in resorption markers in either group.

He compared the results of this pilot study with those for daily PTH treatment at 12 months from the Parathyroid Hormone and Alendronate (PaTH) study (N. Engl. J. Med. 2005;353:555–65).

Once-weekly PTH following daily PTH for 1 month significantly increased spine BMD. However, compared with daily PTH in the PaTh study, “there was no significant increase in trabecular BMD, a small increase in DXA spine BMD, a smaller increase in bone formation markers, and generally a smaller anabolic response,” he said.

Once weekly PTH may not be frequent enough. A longer loading period may be necessary, he noted. In terms of adverse events, there was one case of chest pain in the placebo group, and there were four mild cases of hypercalcemia in the PTH group.

Dr. Black disclosed that he has significant financial relationships with Novartis, Merck & Co., Hoffmann-La Roche Inc., and GlaxoSmithKline.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Premenopausal vasomotor symptoms, particularly night sweats, are a previously unrecognized risk factor for low bone mineral density and enhanced bone turnover in infertile women—and probably in fertile women as well, although this has not yet been confirmed, according to Dr. Lubna Pal of the Albert Einstein College of Medicine, N.Y.

Her study won the prize paper from the Society for Reproductive Endocrinology and Infertility at the annual meeting of the American Society for Reproductive Medicine. Based on these data, “I would advise providers to specifically ask about vasomotor symptoms in premenopausal women and, for those who are symptomatic, to focus on unmasking additional factors that may enhance their fracture risk, such as low body mass; family or personal history of fractures; or smoking,” she said in an interview. “I don't think we are there yet in terms of recommending bone density screening for this population … but these women need to be advised that a further deterioration in their bone density parameters is likely to occur in the postmenopausal period, and measures to optimize skeletal health should be addressed now rather than later.”

The cross-sectional study included 86 premenopausal infertile women aged 42 years or younger without premature ovarian failure or oophorectomy. A questionnaire was used to ask about the presence and frequency of vasomotor symptoms, including hot flashes and night sweats.

The study also measured subjects' bone mineral density (BMD) and levels of serum N-telopeptide (NTx), a marker of bone turnover. A total of 12% of respondents reported one or both vasomotor symptoms, and 21% of respondents had evidence of low BMD, Dr. Pal reported.

There was a highly significant correlation between vasomotor symptoms and low BMD, with 62.5% of symptomatic women showing evidence of low BMD, compared with 14% of asymptomatic women (odds ratio 10.18). Similarly, 36% of women with low BMD reported vasomotor symptoms, compared with 5% of those with normal BMD.

After controlling for age, body mass index, menstrual regularity, race, and smoking, the study found that vasomotor symptoms (night sweats and/or hot flashes) were independent predictors of low bone density in the study population. The magnitude of this association was most robust for night sweats, with an adjusted odds ratio (AOR) of 52.47, followed by both symptoms combined (AOR 24.10), and then hot flashes alone (AOR 15.10).

The presence of night sweats was also an independent predictor of bone turnover, with higher levels of serum NTx seen in symptomatic compared with asymptomatic women, she said.

Levels of inhibin B, a marker of ovarian reserve, were also significantly lower in women with night sweats compared with asymptomatic women, she said.

NEW ORLEANS — Premenopausal vasomotor symptoms, particularly night sweats, are a previously unrecognized risk factor for low bone mineral density and enhanced bone turnover in infertile women—and probably in fertile women as well, although this has not yet been confirmed, according to Dr. Lubna Pal of the Albert Einstein College of Medicine, N.Y.

Her study won the prize paper from the Society for Reproductive Endocrinology and Infertility at the annual meeting of the American Society for Reproductive Medicine. Based on these data, “I would advise providers to specifically ask about vasomotor symptoms in premenopausal women and, for those who are symptomatic, to focus on unmasking additional factors that may enhance their fracture risk, such as low body mass; family or personal history of fractures; or smoking,” she said in an interview. “I don't think we are there yet in terms of recommending bone density screening for this population … but these women need to be advised that a further deterioration in their bone density parameters is likely to occur in the postmenopausal period, and measures to optimize skeletal health should be addressed now rather than later.”

The cross-sectional study included 86 premenopausal infertile women aged 42 years or younger without premature ovarian failure or oophorectomy. A questionnaire was used to ask about the presence and frequency of vasomotor symptoms, including hot flashes and night sweats.

The study also measured subjects' bone mineral density (BMD) and levels of serum N-telopeptide (NTx), a marker of bone turnover. A total of 12% of respondents reported one or both vasomotor symptoms, and 21% of respondents had evidence of low BMD, Dr. Pal reported.

There was a highly significant correlation between vasomotor symptoms and low BMD, with 62.5% of symptomatic women showing evidence of low BMD, compared with 14% of asymptomatic women (odds ratio 10.18). Similarly, 36% of women with low BMD reported vasomotor symptoms, compared with 5% of those with normal BMD.

After controlling for age, body mass index, menstrual regularity, race, and smoking, the study found that vasomotor symptoms (night sweats and/or hot flashes) were independent predictors of low bone density in the study population. The magnitude of this association was most robust for night sweats, with an adjusted odds ratio (AOR) of 52.47, followed by both symptoms combined (AOR 24.10), and then hot flashes alone (AOR 15.10).

The presence of night sweats was also an independent predictor of bone turnover, with higher levels of serum NTx seen in symptomatic compared with asymptomatic women, she said.

Levels of inhibin B, a marker of ovarian reserve, were also significantly lower in women with night sweats compared with asymptomatic women, she said.

NEW ORLEANS — Premenopausal vasomotor symptoms, particularly night sweats, are a previously unrecognized risk factor for low bone mineral density and enhanced bone turnover in infertile women—and probably in fertile women as well, although this has not yet been confirmed, according to Dr. Lubna Pal of the Albert Einstein College of Medicine, N.Y.

Her study won the prize paper from the Society for Reproductive Endocrinology and Infertility at the annual meeting of the American Society for Reproductive Medicine. Based on these data, “I would advise providers to specifically ask about vasomotor symptoms in premenopausal women and, for those who are symptomatic, to focus on unmasking additional factors that may enhance their fracture risk, such as low body mass; family or personal history of fractures; or smoking,” she said in an interview. “I don't think we are there yet in terms of recommending bone density screening for this population … but these women need to be advised that a further deterioration in their bone density parameters is likely to occur in the postmenopausal period, and measures to optimize skeletal health should be addressed now rather than later.”

The cross-sectional study included 86 premenopausal infertile women aged 42 years or younger without premature ovarian failure or oophorectomy. A questionnaire was used to ask about the presence and frequency of vasomotor symptoms, including hot flashes and night sweats.

The study also measured subjects' bone mineral density (BMD) and levels of serum N-telopeptide (NTx), a marker of bone turnover. A total of 12% of respondents reported one or both vasomotor symptoms, and 21% of respondents had evidence of low BMD, Dr. Pal reported.

There was a highly significant correlation between vasomotor symptoms and low BMD, with 62.5% of symptomatic women showing evidence of low BMD, compared with 14% of asymptomatic women (odds ratio 10.18). Similarly, 36% of women with low BMD reported vasomotor symptoms, compared with 5% of those with normal BMD.

After controlling for age, body mass index, menstrual regularity, race, and smoking, the study found that vasomotor symptoms (night sweats and/or hot flashes) were independent predictors of low bone density in the study population. The magnitude of this association was most robust for night sweats, with an adjusted odds ratio (AOR) of 52.47, followed by both symptoms combined (AOR 24.10), and then hot flashes alone (AOR 15.10).

The presence of night sweats was also an independent predictor of bone turnover, with higher levels of serum NTx seen in symptomatic compared with asymptomatic women, she said.

Levels of inhibin B, a marker of ovarian reserve, were also significantly lower in women with night sweats compared with asymptomatic women, she said.

WASHINGTON — Percutaneous vertebroplasty, while effective for relieving pain, has not been shown to prevent new fractures, Dr. Gregg H. Zoarski said in a state of the art review at a symposium sponsored by the Society of Interventional Radiology.

The procedure works in 85%–95% of patients who have pain localized to one or two nonsclerotic vertebrae and osteoporotic fractures that have occurred within less than 2–3 months. When pain is not localized and there are no observable deformities on imaging or fractures have been present for over 1 year, patients seldom respond well to vertebroplasty, Dr. Zoarski said.

Vertebroplasty also can be used to relieve pain caused by soft tumors in the vertebrae, including myelomas. For patients with neoplastic fractures, pain relief ranges from 60% to 90%, said Dr. Zoarski, professor of diagnostic radiology at the University of Maryland, Baltimore, and director of diagnostic and interventional radiology at the University of Maryland Hospital.

In addition, vertebroplasty and kyphoplasty are “tremendously safe procedures,” according to Dr. Zoarski. “Minor complications should be less than 3% and major complications should be well less than 1%,” he stated. Less clear is whether vertebroplasty, like surgical intervention, actually increases the risk of adjacent vertebral fractures.

In small follow-up studies, there was no statistically significant increase in adjacent fractures with vertebroplasty. A retrospective study of 177 patients, however, found a significantly higher rate of adjacent fractures within 30 days of the procedure, and 67% of new fractures occurred adjacent to treated vertebrae, he said.

The natural history of osteoporosis and nonuniform stress within the spine may create a “hot spot” where subsequent fractures are likely to occur, irrespective of intervention. Biomechanical studies are uneven in terms of predicting fracture location.

With regard to both vertebroplasty and kyphoplasty, “I think we have to conclude that there is mixed data on this and we cannot clearly state whether the procedure is going to prevent or cause adjacent fractures,” Dr. Zoarski said. The need for vertebroplasty or other interventional treatments is relatively high, especially because surgery isn't an option for many patients with poor bony substrate or comorbidities.

Noninterventional alternatives have their own complications. Bed rest can exacerbate bone deterioration and decrease patient strength. Bracing has compliance problems, and removal of the brace causes patients “to regress to the same level of deformity that they would have [had] without the brace.” Medications for pain can interact with other drugs as well as directly contribute to morbidity. Dr. Zoarski stated that he had no financial relationships to disclose in regard to percutaneous vertebroplasty.

WASHINGTON — Percutaneous vertebroplasty, while effective for relieving pain, has not been shown to prevent new fractures, Dr. Gregg H. Zoarski said in a state of the art review at a symposium sponsored by the Society of Interventional Radiology.

The procedure works in 85%–95% of patients who have pain localized to one or two nonsclerotic vertebrae and osteoporotic fractures that have occurred within less than 2–3 months. When pain is not localized and there are no observable deformities on imaging or fractures have been present for over 1 year, patients seldom respond well to vertebroplasty, Dr. Zoarski said.

Vertebroplasty also can be used to relieve pain caused by soft tumors in the vertebrae, including myelomas. For patients with neoplastic fractures, pain relief ranges from 60% to 90%, said Dr. Zoarski, professor of diagnostic radiology at the University of Maryland, Baltimore, and director of diagnostic and interventional radiology at the University of Maryland Hospital.

In addition, vertebroplasty and kyphoplasty are “tremendously safe procedures,” according to Dr. Zoarski. “Minor complications should be less than 3% and major complications should be well less than 1%,” he stated. Less clear is whether vertebroplasty, like surgical intervention, actually increases the risk of adjacent vertebral fractures.

In small follow-up studies, there was no statistically significant increase in adjacent fractures with vertebroplasty. A retrospective study of 177 patients, however, found a significantly higher rate of adjacent fractures within 30 days of the procedure, and 67% of new fractures occurred adjacent to treated vertebrae, he said.

The natural history of osteoporosis and nonuniform stress within the spine may create a “hot spot” where subsequent fractures are likely to occur, irrespective of intervention. Biomechanical studies are uneven in terms of predicting fracture location.

With regard to both vertebroplasty and kyphoplasty, “I think we have to conclude that there is mixed data on this and we cannot clearly state whether the procedure is going to prevent or cause adjacent fractures,” Dr. Zoarski said. The need for vertebroplasty or other interventional treatments is relatively high, especially because surgery isn't an option for many patients with poor bony substrate or comorbidities.

Noninterventional alternatives have their own complications. Bed rest can exacerbate bone deterioration and decrease patient strength. Bracing has compliance problems, and removal of the brace causes patients “to regress to the same level of deformity that they would have [had] without the brace.” Medications for pain can interact with other drugs as well as directly contribute to morbidity. Dr. Zoarski stated that he had no financial relationships to disclose in regard to percutaneous vertebroplasty.

WASHINGTON — Percutaneous vertebroplasty, while effective for relieving pain, has not been shown to prevent new fractures, Dr. Gregg H. Zoarski said in a state of the art review at a symposium sponsored by the Society of Interventional Radiology.

The procedure works in 85%–95% of patients who have pain localized to one or two nonsclerotic vertebrae and osteoporotic fractures that have occurred within less than 2–3 months. When pain is not localized and there are no observable deformities on imaging or fractures have been present for over 1 year, patients seldom respond well to vertebroplasty, Dr. Zoarski said.

Vertebroplasty also can be used to relieve pain caused by soft tumors in the vertebrae, including myelomas. For patients with neoplastic fractures, pain relief ranges from 60% to 90%, said Dr. Zoarski, professor of diagnostic radiology at the University of Maryland, Baltimore, and director of diagnostic and interventional radiology at the University of Maryland Hospital.

In addition, vertebroplasty and kyphoplasty are “tremendously safe procedures,” according to Dr. Zoarski. “Minor complications should be less than 3% and major complications should be well less than 1%,” he stated. Less clear is whether vertebroplasty, like surgical intervention, actually increases the risk of adjacent vertebral fractures.

In small follow-up studies, there was no statistically significant increase in adjacent fractures with vertebroplasty. A retrospective study of 177 patients, however, found a significantly higher rate of adjacent fractures within 30 days of the procedure, and 67% of new fractures occurred adjacent to treated vertebrae, he said.

The natural history of osteoporosis and nonuniform stress within the spine may create a “hot spot” where subsequent fractures are likely to occur, irrespective of intervention. Biomechanical studies are uneven in terms of predicting fracture location.

With regard to both vertebroplasty and kyphoplasty, “I think we have to conclude that there is mixed data on this and we cannot clearly state whether the procedure is going to prevent or cause adjacent fractures,” Dr. Zoarski said. The need for vertebroplasty or other interventional treatments is relatively high, especially because surgery isn't an option for many patients with poor bony substrate or comorbidities.

Noninterventional alternatives have their own complications. Bed rest can exacerbate bone deterioration and decrease patient strength. Bracing has compliance problems, and removal of the brace causes patients “to regress to the same level of deformity that they would have [had] without the brace.” Medications for pain can interact with other drugs as well as directly contribute to morbidity. Dr. Zoarski stated that he had no financial relationships to disclose in regard to percutaneous vertebroplasty.

CHICAGO — Low bone-mineral density was associated with exercise-induced myocardial ischemia in a retrospective analysis of more than 1,000 patients.

These are the first study results to show a link between bone mineral density (BMD) and exercise-induced ischemia using exercise echocardiography, Dr. Aaron M. From and his associates said in a poster presented at the annual scientific sessions of the American Heart Association.

Results from prior studies had linked low BMD and an increased risk of stroke, atherosclerosis, and cardiovascular death, said Dr. From, a physician at the Mayo Clinic in Rochester, Minn.

The latest analysis included all patients who underwent dual energy x-ray absorptiometry of the femoral neck at the Mayo Clinic between August 1998 and October 2003 who also had an exercise echocardiography examination for any indication sometime soon after undergoing the bone scan procedure.

The researchers identified 1,142 patients who fulfilled these criteria. All of the patients were referred for both studies by their physicians.

The group included a total of 643 patients with low BMD, including 126 with osteoporosis and 517 with osteopenia. The remaining 499 patients had BMDs in the normal range. The most common reason for the exercise echo examination was chest pain/dyspnea, in 57% of the patients; 6% had known coronary artery disease.

The analysis showed that patients with the lowest BMD (a T score of −4 to −3) had the shortest exercise duration, 5.8 minutes, while patients with the highest T scores (+1 to +2) had the longest exercise duration, 8.9 minutes.

In a multivariate analysis that controlled for baseline clinical and demographic differences, the risk of having exercise-induced ischemia rose by 22% for every one-point decrease in T score (representing one standard-deviation decrease in T score) a statistically significant difference, Dr. From and his associates reported in the poster.

CHICAGO — Low bone-mineral density was associated with exercise-induced myocardial ischemia in a retrospective analysis of more than 1,000 patients.

These are the first study results to show a link between bone mineral density (BMD) and exercise-induced ischemia using exercise echocardiography, Dr. Aaron M. From and his associates said in a poster presented at the annual scientific sessions of the American Heart Association.

Results from prior studies had linked low BMD and an increased risk of stroke, atherosclerosis, and cardiovascular death, said Dr. From, a physician at the Mayo Clinic in Rochester, Minn.

The latest analysis included all patients who underwent dual energy x-ray absorptiometry of the femoral neck at the Mayo Clinic between August 1998 and October 2003 who also had an exercise echocardiography examination for any indication sometime soon after undergoing the bone scan procedure.

The researchers identified 1,142 patients who fulfilled these criteria. All of the patients were referred for both studies by their physicians.

The group included a total of 643 patients with low BMD, including 126 with osteoporosis and 517 with osteopenia. The remaining 499 patients had BMDs in the normal range. The most common reason for the exercise echo examination was chest pain/dyspnea, in 57% of the patients; 6% had known coronary artery disease.

The analysis showed that patients with the lowest BMD (a T score of −4 to −3) had the shortest exercise duration, 5.8 minutes, while patients with the highest T scores (+1 to +2) had the longest exercise duration, 8.9 minutes.

In a multivariate analysis that controlled for baseline clinical and demographic differences, the risk of having exercise-induced ischemia rose by 22% for every one-point decrease in T score (representing one standard-deviation decrease in T score) a statistically significant difference, Dr. From and his associates reported in the poster.

CHICAGO — Low bone-mineral density was associated with exercise-induced myocardial ischemia in a retrospective analysis of more than 1,000 patients.

These are the first study results to show a link between bone mineral density (BMD) and exercise-induced ischemia using exercise echocardiography, Dr. Aaron M. From and his associates said in a poster presented at the annual scientific sessions of the American Heart Association.

Results from prior studies had linked low BMD and an increased risk of stroke, atherosclerosis, and cardiovascular death, said Dr. From, a physician at the Mayo Clinic in Rochester, Minn.

The latest analysis included all patients who underwent dual energy x-ray absorptiometry of the femoral neck at the Mayo Clinic between August 1998 and October 2003 who also had an exercise echocardiography examination for any indication sometime soon after undergoing the bone scan procedure.

The researchers identified 1,142 patients who fulfilled these criteria. All of the patients were referred for both studies by their physicians.

The group included a total of 643 patients with low BMD, including 126 with osteoporosis and 517 with osteopenia. The remaining 499 patients had BMDs in the normal range. The most common reason for the exercise echo examination was chest pain/dyspnea, in 57% of the patients; 6% had known coronary artery disease.

The analysis showed that patients with the lowest BMD (a T score of −4 to −3) had the shortest exercise duration, 5.8 minutes, while patients with the highest T scores (+1 to +2) had the longest exercise duration, 8.9 minutes.

In a multivariate analysis that controlled for baseline clinical and demographic differences, the risk of having exercise-induced ischemia rose by 22% for every one-point decrease in T score (representing one standard-deviation decrease in T score) a statistically significant difference, Dr. From and his associates reported in the poster.

PHILADELPHIA — The investigative osteoporosis therapy denosumab appears to improve several measures of bone geometry, which are factors in bone strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a post hoc analysis of phase II trial data, researchers found that denosumab therapy was associated with increased bone cross-sectional areas, cortical thickness, and measures of bending strength and stability against high compressive stresses. “These positive changes in structural geometry support the likelihood that treatment improves the mechanical strength of the proximal femur,” said Dr. Thomas J. Beck, professor of radiology at Johns Hopkins University, Baltimore.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand, the primary mediator of osteoclast differentiation, activation, and survival. Denosumab binds to this protein, inhibiting osteoclast differentiation, activation, and survival.

In the phase II study, denosumab therapy was shown to increase bone mineral density (N. Engl. J. Med. 2006;354:821–31) and presumably bone mechanical strength as well.

Bone strength can be altered by changes in bone geometry—the amount and distribution of bone—or by changes in the composition of bone tissue.

The trial data included 39 patients on 60 mg of denosumab every 6 months, 39 subjects on placebo, and 38 patients on open-label alendronate (70 mg once weekly).

The study was funded in part by Amgen Inc. Dr. Beck disclosed that he has significant financial relationships with Merck & Co. Inc., Amgen Inc., and Hologic Inc.

The researchers used hip structural analysis to calculate bone cross-sectional area, section modulus (an indicator of bending strength), estimated cortical thickness, and buckling ratio (an estimate of cortical stability in buckling or against high compressive stresses) from dual-energy x-ray absorptiometry hip scans at baseline and at 12 and 24 months.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the bisector of the neck-shaft angle), and across the shaft (2 cm distal to the midpoint of the lesser trochanter).

For the femoral neck at 24 months, the percent change in bone mineral density (BMD) from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was similar for denosumab and alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo (a positive result, indicating increased strength).

Dr. Beck added that for the inter-trochanteric region at 24 months, the percent change in BMD from baseline was significantly greater among patients receiving denosumab therapy than for those given placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, he reported.

The percent change in section modulus was significantly greater for denosumab than for placebo. The percent change in estimated cortical thickness was significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo.

For the shaft at 24 months, the percent change in BMD from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for alendronate, and the percent change in buckling ratio was significantly lower for denosumab than for alendronate.

PHILADELPHIA — The investigative osteoporosis therapy denosumab appears to improve several measures of bone geometry, which are factors in bone strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a post hoc analysis of phase II trial data, researchers found that denosumab therapy was associated with increased bone cross-sectional areas, cortical thickness, and measures of bending strength and stability against high compressive stresses. “These positive changes in structural geometry support the likelihood that treatment improves the mechanical strength of the proximal femur,” said Dr. Thomas J. Beck, professor of radiology at Johns Hopkins University, Baltimore.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand, the primary mediator of osteoclast differentiation, activation, and survival. Denosumab binds to this protein, inhibiting osteoclast differentiation, activation, and survival.

In the phase II study, denosumab therapy was shown to increase bone mineral density (N. Engl. J. Med. 2006;354:821–31) and presumably bone mechanical strength as well.

Bone strength can be altered by changes in bone geometry—the amount and distribution of bone—or by changes in the composition of bone tissue.

The trial data included 39 patients on 60 mg of denosumab every 6 months, 39 subjects on placebo, and 38 patients on open-label alendronate (70 mg once weekly).

The study was funded in part by Amgen Inc. Dr. Beck disclosed that he has significant financial relationships with Merck & Co. Inc., Amgen Inc., and Hologic Inc.

The researchers used hip structural analysis to calculate bone cross-sectional area, section modulus (an indicator of bending strength), estimated cortical thickness, and buckling ratio (an estimate of cortical stability in buckling or against high compressive stresses) from dual-energy x-ray absorptiometry hip scans at baseline and at 12 and 24 months.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the bisector of the neck-shaft angle), and across the shaft (2 cm distal to the midpoint of the lesser trochanter).

For the femoral neck at 24 months, the percent change in bone mineral density (BMD) from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was similar for denosumab and alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo (a positive result, indicating increased strength).

Dr. Beck added that for the inter-trochanteric region at 24 months, the percent change in BMD from baseline was significantly greater among patients receiving denosumab therapy than for those given placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, he reported.

The percent change in section modulus was significantly greater for denosumab than for placebo. The percent change in estimated cortical thickness was significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo.

For the shaft at 24 months, the percent change in BMD from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for alendronate, and the percent change in buckling ratio was significantly lower for denosumab than for alendronate.

PHILADELPHIA — The investigative osteoporosis therapy denosumab appears to improve several measures of bone geometry, which are factors in bone strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

In a post hoc analysis of phase II trial data, researchers found that denosumab therapy was associated with increased bone cross-sectional areas, cortical thickness, and measures of bending strength and stability against high compressive stresses. “These positive changes in structural geometry support the likelihood that treatment improves the mechanical strength of the proximal femur,” said Dr. Thomas J. Beck, professor of radiology at Johns Hopkins University, Baltimore.

Denosumab is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor kappa B ligand, the primary mediator of osteoclast differentiation, activation, and survival. Denosumab binds to this protein, inhibiting osteoclast differentiation, activation, and survival.

In the phase II study, denosumab therapy was shown to increase bone mineral density (N. Engl. J. Med. 2006;354:821–31) and presumably bone mechanical strength as well.

Bone strength can be altered by changes in bone geometry—the amount and distribution of bone—or by changes in the composition of bone tissue.

The trial data included 39 patients on 60 mg of denosumab every 6 months, 39 subjects on placebo, and 38 patients on open-label alendronate (70 mg once weekly).

The study was funded in part by Amgen Inc. Dr. Beck disclosed that he has significant financial relationships with Merck & Co. Inc., Amgen Inc., and Hologic Inc.

The researchers used hip structural analysis to calculate bone cross-sectional area, section modulus (an indicator of bending strength), estimated cortical thickness, and buckling ratio (an estimate of cortical stability in buckling or against high compressive stresses) from dual-energy x-ray absorptiometry hip scans at baseline and at 12 and 24 months.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the bisector of the neck-shaft angle), and across the shaft (2 cm distal to the midpoint of the lesser trochanter).

For the femoral neck at 24 months, the percent change in bone mineral density (BMD) from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was similar for denosumab and alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo (a positive result, indicating increased strength).

Dr. Beck added that for the inter-trochanteric region at 24 months, the percent change in BMD from baseline was significantly greater among patients receiving denosumab therapy than for those given placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, he reported.

The percent change in section modulus was significantly greater for denosumab than for placebo. The percent change in estimated cortical thickness was significantly greater for denosumab than for placebo, and the percent change in buckling ratio was significantly lower for denosumab than for placebo.

For the shaft at 24 months, the percent change in BMD from baseline was significantly greater for denosumab than for placebo. The percent change in cross-sectional area was significantly greater for denosumab than for alendronate, according to Dr. Beck.

The percent changes in section modulus and estimated cortical thickness were significantly greater for denosumab than for alendronate, and the percent change in buckling ratio was significantly lower for denosumab than for alendronate.