Osteoarthritis

SAN FRANCISCO — Antiresorptive therapy should be continued even in patients showing no apparent response, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Monitoring response with periodic bone mineral density (BMD) testing may be misleading, said Dr. Bauer, of UCSF. Furthermore, studies show that antiresorptive therapy decreases fracture risk even when BMD declines. And a patient whose BMD declines in the first year of therapy will often see an improvement in subsequent years.

Those advocating periodic monitoring cite several potential advantages of the practice, including increases in patient satisfaction, improvements in adherence, and the ability to change to more effective therapy in the presence of a nonresponse.

But Dr. Bauer pointed out that there are no studies demonstrating that monitoring improves patient satisfaction or adherence. While it's true that many patients stop taking drugs to prevent osteoporosis, more than half of those who discontinue do so within 6 months of beginning therapy, he said. Measuring BMD 1–2 years following diagnosis is therefore unlikely to encourage adherence in the majority of patients.

In addition, changes in BMD on subsequent measurements may be misleading. Although BMD is usually considered a very precise measurement, with precision errors in the neighborhood of 1%–2%, some apparent changes in BMD may be due to noise or to small differences in patient position, Dr. Bauer said.

To figure out what changes in BMD measurements are due to chance, Dr. Bauer recommended using the “least significant change” formula. The least significant change in any measurement is defined as three times the measurement's long-term reproducibility. For example, if a dual-energy x-ray absorptiometry (DXA) instrument has a long-term coefficient of variation of 1.5%, its least significant change would be 4.5%, meaning that changes of less than 4.5% from measurement to measurement may well be due to chance.

But even if a patient's BMD truly is declining, that does not necessarily mean that the patient is failing to respond to treatment, since he or she may well have lost more bone without treatment, he added.

And an initial loss of bone during treatment doesn't mean that this loss will continue. Dr. Bauer quoted one study that showed that of patients who lost more than 4% of their BMD during the first year of treatment, 92% gained BMD in the second year, and the average increase during the second year was 4.8%. On the other hand, of patients who gained more than 8% in BMD during the first year, only 36% continue to gain BMD in the second year, and as a whole that group lost 1% of their BMD during that second-year.

An analysis of a clinical trial of alendronate versus placebo compared the patients who lost most BMD while taking alendronate with those who lost most BMD while taking placebo. Fracture risk was reduced by about 50% in those taking alendronate despite their loss of BMD.

Clinicians should consider secondary causes of osteoporosis in patients who are losing BMD despite antiresorptive therapy, Dr. Bauer said. Among the common secondary causes of bone loss are weight loss; medications such as corticosteroids, aromatase inhibitors, and glitazones; inflammatory diseases or myeloma; or malabsorption.

SAN FRANCISCO — Antiresorptive therapy should be continued even in patients showing no apparent response, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Monitoring response with periodic bone mineral density (BMD) testing may be misleading, said Dr. Bauer, of UCSF. Furthermore, studies show that antiresorptive therapy decreases fracture risk even when BMD declines. And a patient whose BMD declines in the first year of therapy will often see an improvement in subsequent years.

Those advocating periodic monitoring cite several potential advantages of the practice, including increases in patient satisfaction, improvements in adherence, and the ability to change to more effective therapy in the presence of a nonresponse.

But Dr. Bauer pointed out that there are no studies demonstrating that monitoring improves patient satisfaction or adherence. While it's true that many patients stop taking drugs to prevent osteoporosis, more than half of those who discontinue do so within 6 months of beginning therapy, he said. Measuring BMD 1–2 years following diagnosis is therefore unlikely to encourage adherence in the majority of patients.

In addition, changes in BMD on subsequent measurements may be misleading. Although BMD is usually considered a very precise measurement, with precision errors in the neighborhood of 1%–2%, some apparent changes in BMD may be due to noise or to small differences in patient position, Dr. Bauer said.

To figure out what changes in BMD measurements are due to chance, Dr. Bauer recommended using the “least significant change” formula. The least significant change in any measurement is defined as three times the measurement's long-term reproducibility. For example, if a dual-energy x-ray absorptiometry (DXA) instrument has a long-term coefficient of variation of 1.5%, its least significant change would be 4.5%, meaning that changes of less than 4.5% from measurement to measurement may well be due to chance.

But even if a patient's BMD truly is declining, that does not necessarily mean that the patient is failing to respond to treatment, since he or she may well have lost more bone without treatment, he added.

And an initial loss of bone during treatment doesn't mean that this loss will continue. Dr. Bauer quoted one study that showed that of patients who lost more than 4% of their BMD during the first year of treatment, 92% gained BMD in the second year, and the average increase during the second year was 4.8%. On the other hand, of patients who gained more than 8% in BMD during the first year, only 36% continue to gain BMD in the second year, and as a whole that group lost 1% of their BMD during that second-year.

An analysis of a clinical trial of alendronate versus placebo compared the patients who lost most BMD while taking alendronate with those who lost most BMD while taking placebo. Fracture risk was reduced by about 50% in those taking alendronate despite their loss of BMD.

Clinicians should consider secondary causes of osteoporosis in patients who are losing BMD despite antiresorptive therapy, Dr. Bauer said. Among the common secondary causes of bone loss are weight loss; medications such as corticosteroids, aromatase inhibitors, and glitazones; inflammatory diseases or myeloma; or malabsorption.

SAN FRANCISCO — Antiresorptive therapy should be continued even in patients showing no apparent response, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Monitoring response with periodic bone mineral density (BMD) testing may be misleading, said Dr. Bauer, of UCSF. Furthermore, studies show that antiresorptive therapy decreases fracture risk even when BMD declines. And a patient whose BMD declines in the first year of therapy will often see an improvement in subsequent years.

Those advocating periodic monitoring cite several potential advantages of the practice, including increases in patient satisfaction, improvements in adherence, and the ability to change to more effective therapy in the presence of a nonresponse.

But Dr. Bauer pointed out that there are no studies demonstrating that monitoring improves patient satisfaction or adherence. While it's true that many patients stop taking drugs to prevent osteoporosis, more than half of those who discontinue do so within 6 months of beginning therapy, he said. Measuring BMD 1–2 years following diagnosis is therefore unlikely to encourage adherence in the majority of patients.

In addition, changes in BMD on subsequent measurements may be misleading. Although BMD is usually considered a very precise measurement, with precision errors in the neighborhood of 1%–2%, some apparent changes in BMD may be due to noise or to small differences in patient position, Dr. Bauer said.

To figure out what changes in BMD measurements are due to chance, Dr. Bauer recommended using the “least significant change” formula. The least significant change in any measurement is defined as three times the measurement's long-term reproducibility. For example, if a dual-energy x-ray absorptiometry (DXA) instrument has a long-term coefficient of variation of 1.5%, its least significant change would be 4.5%, meaning that changes of less than 4.5% from measurement to measurement may well be due to chance.

But even if a patient's BMD truly is declining, that does not necessarily mean that the patient is failing to respond to treatment, since he or she may well have lost more bone without treatment, he added.

And an initial loss of bone during treatment doesn't mean that this loss will continue. Dr. Bauer quoted one study that showed that of patients who lost more than 4% of their BMD during the first year of treatment, 92% gained BMD in the second year, and the average increase during the second year was 4.8%. On the other hand, of patients who gained more than 8% in BMD during the first year, only 36% continue to gain BMD in the second year, and as a whole that group lost 1% of their BMD during that second-year.

An analysis of a clinical trial of alendronate versus placebo compared the patients who lost most BMD while taking alendronate with those who lost most BMD while taking placebo. Fracture risk was reduced by about 50% in those taking alendronate despite their loss of BMD.

Clinicians should consider secondary causes of osteoporosis in patients who are losing BMD despite antiresorptive therapy, Dr. Bauer said. Among the common secondary causes of bone loss are weight loss; medications such as corticosteroids, aromatase inhibitors, and glitazones; inflammatory diseases or myeloma; or malabsorption.

MIAMI — Weight and type of sport played by Division I varsity female athletes were significant predictors of bone mineral density measurements, according to a study presented at the annual meeting of the American Medical Society for Sports Medicine.

Dr. Willa Fornetti performed a cross-sectional analysis of 103 female athletes in gymnastics, softball, running, track, field hockey, rowing, swimming/diving, and volleyball at Michigan State University.

“BMI was markedly similar among groups—not what we anticipated. The runners were slightly lower than others, though,” said Dr. Fornetti, of Michigan State University, East Lansing.

As might be expected, gymnasts had the lowest mean height, and volleyball players had the highest. Runners and gymnasts had the lowest weights and fat-free mass, as well as the highest percentage of menstrual dysfunction.

Dr. Fornetti used dual-energy x-ray absorptiometry to measure total body, lumbar spine, pelvic, and average right/left leg BMD. She compared BMD measurements between athletes involved in sports by using analyses of covariance. She also determined significant predictors of BMD for each site through a stepwise regression analysis.

The 6 athletes with amenorrhea and 18 with oligomenorrhea had statistically significant lower bone mineral density than did other participants, Dr. Fornetti said.

The World Health Organization defines osteopenia as a bone density between 1 and 2.5 standard deviations below the bone density of a normal young adult.

“The good news is that none of our athletes met WHO criteria for osteopenia, regardless of menstrual function,” Dr. Fornetti said.

Runners, swimmers, and divers had significantly lower BMD than the other athletes. Runners also had the lowest mean lumbar spine BMD. Pelvic BMD was lower for runners, swimmers, and divers, Dr. Fornetti said. “Runners had significantly lower BMD at every site, except average leg score, versus athletes in field hockey, softball, and volleyball.”

Limitations of the study include its lack of data on nutrition and eating disorders, and history of training or injury. A large number of participants, multiple-site BMD measurements, and an ability to compare different types of sports are among its strengths, Dr. Fornetti said.

Because lower body weight was associated with lower BMD, “it can be used to screen runners, swimmers and divers,” Dr. Fornetti said. She added that clinicians should consider weight and type of sport played by a female varsity athlete when evaluating bone health.

MIAMI — Weight and type of sport played by Division I varsity female athletes were significant predictors of bone mineral density measurements, according to a study presented at the annual meeting of the American Medical Society for Sports Medicine.

Dr. Willa Fornetti performed a cross-sectional analysis of 103 female athletes in gymnastics, softball, running, track, field hockey, rowing, swimming/diving, and volleyball at Michigan State University.

“BMI was markedly similar among groups—not what we anticipated. The runners were slightly lower than others, though,” said Dr. Fornetti, of Michigan State University, East Lansing.

As might be expected, gymnasts had the lowest mean height, and volleyball players had the highest. Runners and gymnasts had the lowest weights and fat-free mass, as well as the highest percentage of menstrual dysfunction.

Dr. Fornetti used dual-energy x-ray absorptiometry to measure total body, lumbar spine, pelvic, and average right/left leg BMD. She compared BMD measurements between athletes involved in sports by using analyses of covariance. She also determined significant predictors of BMD for each site through a stepwise regression analysis.

The 6 athletes with amenorrhea and 18 with oligomenorrhea had statistically significant lower bone mineral density than did other participants, Dr. Fornetti said.

The World Health Organization defines osteopenia as a bone density between 1 and 2.5 standard deviations below the bone density of a normal young adult.

“The good news is that none of our athletes met WHO criteria for osteopenia, regardless of menstrual function,” Dr. Fornetti said.

Runners, swimmers, and divers had significantly lower BMD than the other athletes. Runners also had the lowest mean lumbar spine BMD. Pelvic BMD was lower for runners, swimmers, and divers, Dr. Fornetti said. “Runners had significantly lower BMD at every site, except average leg score, versus athletes in field hockey, softball, and volleyball.”

Limitations of the study include its lack of data on nutrition and eating disorders, and history of training or injury. A large number of participants, multiple-site BMD measurements, and an ability to compare different types of sports are among its strengths, Dr. Fornetti said.

Because lower body weight was associated with lower BMD, “it can be used to screen runners, swimmers and divers,” Dr. Fornetti said. She added that clinicians should consider weight and type of sport played by a female varsity athlete when evaluating bone health.

MIAMI — Weight and type of sport played by Division I varsity female athletes were significant predictors of bone mineral density measurements, according to a study presented at the annual meeting of the American Medical Society for Sports Medicine.

Dr. Willa Fornetti performed a cross-sectional analysis of 103 female athletes in gymnastics, softball, running, track, field hockey, rowing, swimming/diving, and volleyball at Michigan State University.

“BMI was markedly similar among groups—not what we anticipated. The runners were slightly lower than others, though,” said Dr. Fornetti, of Michigan State University, East Lansing.

As might be expected, gymnasts had the lowest mean height, and volleyball players had the highest. Runners and gymnasts had the lowest weights and fat-free mass, as well as the highest percentage of menstrual dysfunction.

Dr. Fornetti used dual-energy x-ray absorptiometry to measure total body, lumbar spine, pelvic, and average right/left leg BMD. She compared BMD measurements between athletes involved in sports by using analyses of covariance. She also determined significant predictors of BMD for each site through a stepwise regression analysis.

The 6 athletes with amenorrhea and 18 with oligomenorrhea had statistically significant lower bone mineral density than did other participants, Dr. Fornetti said.

The World Health Organization defines osteopenia as a bone density between 1 and 2.5 standard deviations below the bone density of a normal young adult.

“The good news is that none of our athletes met WHO criteria for osteopenia, regardless of menstrual function,” Dr. Fornetti said.

Runners, swimmers, and divers had significantly lower BMD than the other athletes. Runners also had the lowest mean lumbar spine BMD. Pelvic BMD was lower for runners, swimmers, and divers, Dr. Fornetti said. “Runners had significantly lower BMD at every site, except average leg score, versus athletes in field hockey, softball, and volleyball.”

Limitations of the study include its lack of data on nutrition and eating disorders, and history of training or injury. A large number of participants, multiple-site BMD measurements, and an ability to compare different types of sports are among its strengths, Dr. Fornetti said.

Because lower body weight was associated with lower BMD, “it can be used to screen runners, swimmers and divers,” Dr. Fornetti said. She added that clinicians should consider weight and type of sport played by a female varsity athlete when evaluating bone health.

BOSTON — Intermittent intravenous ibandronate is at least as effective as daily oral ibandronate for increasing bone mineral density and may be preferable to oral dosing in patients with esophageal disease or compliance problems.

There are no fracture data for the intravenous dosing schedule, but the risk reduction that has been shown with oral ibandronate can probably be extrapolated to the intravenous form of the drug, Dr. Mone Zaidi said at the annual meeting of the Endocrine Society.

Oral ibandronate has been shown to reduce the risk of new vertebral fractures by up to 60% (Curr. Med. Res. Opin. 2005;21:391–401; J. Bone Miner. Res. 2004;19:1241–9).

“If you can show equivalence or superiority in bone mineral density changes to [the form] with proven fracture data, which we have done, I think everyone would agree that you can extrapolate that data,” said Dr. Zaidi, director of the Mount Sinai Bone Program, Mount Sinai School of Medicine, New York.

Dr. Zaidi presented 2-year bone mineral density (BMD) data from the ibandronate Dosing Intravenous Administration trial, a Roche-sponsored phase III study that compared two doses of intravenous ibandronate (2 mg every 2 months and 3 mg every 3 months) with the approved oral dosing schedule (2.5 mg daily). The study group included 1,400 postmenopausal women with low bone mass (T-scores of −3.3 for total spine and −2 for hip).

After 2 years, BMD at the lumbar spine increased significantly more in both intravenous groups than in the oral group (mean increase 6.4% for the 2 mg IV dose, 6.3% for the 3 mg IV dose, and 4.8% for the oral dose).

BMD increased similarly at all other sites measured, with consistently greater gains in both intravenous groups than in the oral group, Dr. Zaidi said.

At 2 years, the incidence of adverse events was similar across all groups. Flulike illnesses and gastrointestinal intolerance were seen primarily in the first year, with only slight increases in cumulative numbers during the second year.

There was no osteonecrosis of the jaw. Renal and urinary incidents were uncommon and similar across groups.

Fracture incident, which was reported as an adverse event, was low and similar in all groups, although Dr. Zaidi stressed that the study was not powered to prove fracture risk reduction.

The intermittent dosing would also be “a great way” to ensure compliance, according to Dr. Zaidi.

BOSTON — Intermittent intravenous ibandronate is at least as effective as daily oral ibandronate for increasing bone mineral density and may be preferable to oral dosing in patients with esophageal disease or compliance problems.

There are no fracture data for the intravenous dosing schedule, but the risk reduction that has been shown with oral ibandronate can probably be extrapolated to the intravenous form of the drug, Dr. Mone Zaidi said at the annual meeting of the Endocrine Society.

Oral ibandronate has been shown to reduce the risk of new vertebral fractures by up to 60% (Curr. Med. Res. Opin. 2005;21:391–401; J. Bone Miner. Res. 2004;19:1241–9).

“If you can show equivalence or superiority in bone mineral density changes to [the form] with proven fracture data, which we have done, I think everyone would agree that you can extrapolate that data,” said Dr. Zaidi, director of the Mount Sinai Bone Program, Mount Sinai School of Medicine, New York.

Dr. Zaidi presented 2-year bone mineral density (BMD) data from the ibandronate Dosing Intravenous Administration trial, a Roche-sponsored phase III study that compared two doses of intravenous ibandronate (2 mg every 2 months and 3 mg every 3 months) with the approved oral dosing schedule (2.5 mg daily). The study group included 1,400 postmenopausal women with low bone mass (T-scores of −3.3 for total spine and −2 for hip).

After 2 years, BMD at the lumbar spine increased significantly more in both intravenous groups than in the oral group (mean increase 6.4% for the 2 mg IV dose, 6.3% for the 3 mg IV dose, and 4.8% for the oral dose).

BMD increased similarly at all other sites measured, with consistently greater gains in both intravenous groups than in the oral group, Dr. Zaidi said.

At 2 years, the incidence of adverse events was similar across all groups. Flulike illnesses and gastrointestinal intolerance were seen primarily in the first year, with only slight increases in cumulative numbers during the second year.

There was no osteonecrosis of the jaw. Renal and urinary incidents were uncommon and similar across groups.

Fracture incident, which was reported as an adverse event, was low and similar in all groups, although Dr. Zaidi stressed that the study was not powered to prove fracture risk reduction.

The intermittent dosing would also be “a great way” to ensure compliance, according to Dr. Zaidi.

BOSTON — Intermittent intravenous ibandronate is at least as effective as daily oral ibandronate for increasing bone mineral density and may be preferable to oral dosing in patients with esophageal disease or compliance problems.

There are no fracture data for the intravenous dosing schedule, but the risk reduction that has been shown with oral ibandronate can probably be extrapolated to the intravenous form of the drug, Dr. Mone Zaidi said at the annual meeting of the Endocrine Society.

Oral ibandronate has been shown to reduce the risk of new vertebral fractures by up to 60% (Curr. Med. Res. Opin. 2005;21:391–401; J. Bone Miner. Res. 2004;19:1241–9).

“If you can show equivalence or superiority in bone mineral density changes to [the form] with proven fracture data, which we have done, I think everyone would agree that you can extrapolate that data,” said Dr. Zaidi, director of the Mount Sinai Bone Program, Mount Sinai School of Medicine, New York.

Dr. Zaidi presented 2-year bone mineral density (BMD) data from the ibandronate Dosing Intravenous Administration trial, a Roche-sponsored phase III study that compared two doses of intravenous ibandronate (2 mg every 2 months and 3 mg every 3 months) with the approved oral dosing schedule (2.5 mg daily). The study group included 1,400 postmenopausal women with low bone mass (T-scores of −3.3 for total spine and −2 for hip).

After 2 years, BMD at the lumbar spine increased significantly more in both intravenous groups than in the oral group (mean increase 6.4% for the 2 mg IV dose, 6.3% for the 3 mg IV dose, and 4.8% for the oral dose).

BMD increased similarly at all other sites measured, with consistently greater gains in both intravenous groups than in the oral group, Dr. Zaidi said.

At 2 years, the incidence of adverse events was similar across all groups. Flulike illnesses and gastrointestinal intolerance were seen primarily in the first year, with only slight increases in cumulative numbers during the second year.

There was no osteonecrosis of the jaw. Renal and urinary incidents were uncommon and similar across groups.

Fracture incident, which was reported as an adverse event, was low and similar in all groups, although Dr. Zaidi stressed that the study was not powered to prove fracture risk reduction.

The intermittent dosing would also be “a great way” to ensure compliance, according to Dr. Zaidi.

BOSTON — The investigational antiresorptive denosumab is at least as effective as alendronate for increasing bone mineral density in postmenopausal women, Dr. Nelson Watts said at the annual meeting of the Endocrine Society.

The drug inhibits RANKL (receptor activator of nuclear factor kappa B ligand), which is a mediator of the resorptive phase of bone remodeling. Interfering with the binding of RANK to its ligand inhibits the differentiation and proliferation of osteoclasts, thus reducing bone turnover, said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati. He presented the 24-month bone mineral density (BMD) results of a phase II safety and efficacy trial of denosumab. The trial compared denosumab with open-label alendronate, 70 mg weekly, and placebo in 412 postmenopausal women with low bone mass. Three doses of denosumab were tested; Dr. Watts discussed the results for 60-mg doses given subcutaneously every 6 months. This dosage was selected for evaluation in phase III clinical testing.

At 24 months, denosumab was associated with a significantly higher mean increase in BMD than was alendronate at all skeletal sites measured, including lumbar spine (7% vs. 6%), total hip (5% vs. 3.5%), and distal radius (1.75% vs. 0.5%).

Adverse events occurred in about 93% of patients in both groups, and the types of events were not significantly different, with the exception of more dyspepsia among those taking alendronate, Dr. Watts said. There were no signs of increased immune problems, infections, or neoplasms in either group.

In a post hoc analysis, significantly more women in the denosumab group experienced a gain of more than 3% in BMD at each site measured, including lumbar spine (93% vs. 87%), total hip (80% vs. 56%), femoral neck (60% vs. 41%), and distal radius (25% vs. 11%).

The trial was sponsored by Amgen Inc., which manufactures denosumab.

BOSTON — The investigational antiresorptive denosumab is at least as effective as alendronate for increasing bone mineral density in postmenopausal women, Dr. Nelson Watts said at the annual meeting of the Endocrine Society.

The drug inhibits RANKL (receptor activator of nuclear factor kappa B ligand), which is a mediator of the resorptive phase of bone remodeling. Interfering with the binding of RANK to its ligand inhibits the differentiation and proliferation of osteoclasts, thus reducing bone turnover, said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati. He presented the 24-month bone mineral density (BMD) results of a phase II safety and efficacy trial of denosumab. The trial compared denosumab with open-label alendronate, 70 mg weekly, and placebo in 412 postmenopausal women with low bone mass. Three doses of denosumab were tested; Dr. Watts discussed the results for 60-mg doses given subcutaneously every 6 months. This dosage was selected for evaluation in phase III clinical testing.

At 24 months, denosumab was associated with a significantly higher mean increase in BMD than was alendronate at all skeletal sites measured, including lumbar spine (7% vs. 6%), total hip (5% vs. 3.5%), and distal radius (1.75% vs. 0.5%).

Adverse events occurred in about 93% of patients in both groups, and the types of events were not significantly different, with the exception of more dyspepsia among those taking alendronate, Dr. Watts said. There were no signs of increased immune problems, infections, or neoplasms in either group.

In a post hoc analysis, significantly more women in the denosumab group experienced a gain of more than 3% in BMD at each site measured, including lumbar spine (93% vs. 87%), total hip (80% vs. 56%), femoral neck (60% vs. 41%), and distal radius (25% vs. 11%).

The trial was sponsored by Amgen Inc., which manufactures denosumab.

BOSTON — The investigational antiresorptive denosumab is at least as effective as alendronate for increasing bone mineral density in postmenopausal women, Dr. Nelson Watts said at the annual meeting of the Endocrine Society.

The drug inhibits RANKL (receptor activator of nuclear factor kappa B ligand), which is a mediator of the resorptive phase of bone remodeling. Interfering with the binding of RANK to its ligand inhibits the differentiation and proliferation of osteoclasts, thus reducing bone turnover, said Dr. Watts, director of the bone health and osteoporosis center at the University of Cincinnati. He presented the 24-month bone mineral density (BMD) results of a phase II safety and efficacy trial of denosumab. The trial compared denosumab with open-label alendronate, 70 mg weekly, and placebo in 412 postmenopausal women with low bone mass. Three doses of denosumab were tested; Dr. Watts discussed the results for 60-mg doses given subcutaneously every 6 months. This dosage was selected for evaluation in phase III clinical testing.

At 24 months, denosumab was associated with a significantly higher mean increase in BMD than was alendronate at all skeletal sites measured, including lumbar spine (7% vs. 6%), total hip (5% vs. 3.5%), and distal radius (1.75% vs. 0.5%).

Adverse events occurred in about 93% of patients in both groups, and the types of events were not significantly different, with the exception of more dyspepsia among those taking alendronate, Dr. Watts said. There were no signs of increased immune problems, infections, or neoplasms in either group.

In a post hoc analysis, significantly more women in the denosumab group experienced a gain of more than 3% in BMD at each site measured, including lumbar spine (93% vs. 87%), total hip (80% vs. 56%), femoral neck (60% vs. 41%), and distal radius (25% vs. 11%).

The trial was sponsored by Amgen Inc., which manufactures denosumab.

SAN FRANCISCO — Finding one possible cause of secondary osteoporosis does not mean there aren't other causes as well, Dr. Diana Antoniucci reported at a meeting on osteoporosis sponsored by the University of California, San Francisco.

“Having one secondary cause of osteoporosis does not preclude you from having another, so even if one contributor is obvious from the history, you can still consider laboratory testing,” said Dr. Antoniucci, of UCSF. (See sidebar for suggestions on which tests to order.) She listed four frequent causes of secondary osteoporosis for physicians to consider.

Glucocorticoid Use

This is the most common cause of drug-induced osteoporosis. In these patients, prevention is clearly the best strategy. All patients should be taking supplemental calcium and vitamin D, Dr. Antoniucci said, and if the patient has already been diagnosed with osteoporosis or is otherwise at high risk, the physician should measure bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). Clinical trials have shown that bisphosphonates halt bone loss and reduce fractures in patients taking glucocorticoids, and alendronate and risedronate are both approved for this indication. They should be considered for any patient on glucocorticoids with low BMD.

Vitamin D Deficiency

This deficiency is very common in the general population. Depending on the study population, the prevalence appears to range between 9% and 50%.

When severe, vitamin D deficiency is associated with osteomalacia, which is indistinguishable from low bone density on DXA. Less-severe vitamin D deficiency is associated with secondary hyperparathyroidism.

One difficulty in the assessment and treatment of vitamin D deficiency is that there is no general agreement as to what constitutes a sufficient level of 25-hydroxyvitamin D, Dr. Antoniucci noted. A level of 20 ng/mL appears to be necessary for normal parathyroid dynamics, 32–36 ng/mL appears to be necessary for maximal intestinal calcium transport, and 30–40 ng/mL is the level that several randomized controlled trials have determined is necessary for fracture reduction.

“The good news is that vitamin D insufficiency is treatable,” Dr. Antoniucci said. “Replacement reestablishes vitamin D stores, and it improves bone mineral density because it allows optimal calcification of preexisting osteoid.”

Celiac Disease

Somewhere between 9% and 12% of patients with osteoporosis also have celiac disease. Conversely, about 50% of patients with celiac disease have a BMD that is two standard deviations or more under the mean. Among patients with celiac disease, those with a low BMD are more likely to have villous atrophy, an indication of more severe disease. The pathogenesis of bone disease in these patients is likely multifactorial, according to Dr. Antoniucci. They tend to have worse calcium absorption from the gut, especially before their disease is diagnosed, which can be many years in some patients. They also can have vitamin D deficiency from secondary hyperparathyroidism. Some women with celiac disease also have infertility and amenorrhea, both of which can lead to poor bone health.

At least one study has demonstrated that among patients with celiac disease, a strict gluten-free diet over the period of a year can improve bone mass in both men and women (Arch. Intern. Med. 2005;165:393–9). The authors of that study concluded that it's worth screening patients with unexplained osteoporosis for celiac disease. Dr. Antoniucci is not so sure that that's a good idea. “First of all, what exactly is 'unexplained osteoporosis'? And secondly, it might be a very expensive way to be treating the disease,” she said.

Androgen Deprivation Therapy

The longer a man is on this common therapy forprostate cancer, the greater his BMD loss and the greater his chance of fracture. After 10 years on androgen deprivation therapy, about 20% of men will have experienced a fracture, a risk fivefold greater than in age-matched controls. Slender white men appear to be at greatest risk, she said, noting that both pamidronate and zoledronate have been shown to prevent bone loss caused by androgen deprivation therapy.

Labs to Detect Secondary Osteoporosis

There is no consensus on whom to evaluate for secondary osteoporosis, said Dr. Antoniucci. However, “most people would agree that we should evaluate virtually all men with low T-scores, premenopausal women with low Z-scores or fragility fractures, and postmenopausal women,” she said.

Dr. Antoniucci said a standard laboratory work-up should include:

▸ Electrolyte levels.

▸ Renal and hepatic function.

▸ Complete blood count.

▸ 24-hour urine calcium excretion (which can provide important information if the result is very high or very low).

▸ 25-hydroxyvitamin D levels.

▸ Testosterone levels.

▸ Thyroid-stimulating hormone levels (in patients on thyroid hormone replacement).

Additional tests are dictated by the patient's history and physical exam and the physician's clinical judgment.

SAN FRANCISCO — Finding one possible cause of secondary osteoporosis does not mean there aren't other causes as well, Dr. Diana Antoniucci reported at a meeting on osteoporosis sponsored by the University of California, San Francisco.

“Having one secondary cause of osteoporosis does not preclude you from having another, so even if one contributor is obvious from the history, you can still consider laboratory testing,” said Dr. Antoniucci, of UCSF. (See sidebar for suggestions on which tests to order.) She listed four frequent causes of secondary osteoporosis for physicians to consider.

Glucocorticoid Use

This is the most common cause of drug-induced osteoporosis. In these patients, prevention is clearly the best strategy. All patients should be taking supplemental calcium and vitamin D, Dr. Antoniucci said, and if the patient has already been diagnosed with osteoporosis or is otherwise at high risk, the physician should measure bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). Clinical trials have shown that bisphosphonates halt bone loss and reduce fractures in patients taking glucocorticoids, and alendronate and risedronate are both approved for this indication. They should be considered for any patient on glucocorticoids with low BMD.

Vitamin D Deficiency

This deficiency is very common in the general population. Depending on the study population, the prevalence appears to range between 9% and 50%.

When severe, vitamin D deficiency is associated with osteomalacia, which is indistinguishable from low bone density on DXA. Less-severe vitamin D deficiency is associated with secondary hyperparathyroidism.

One difficulty in the assessment and treatment of vitamin D deficiency is that there is no general agreement as to what constitutes a sufficient level of 25-hydroxyvitamin D, Dr. Antoniucci noted. A level of 20 ng/mL appears to be necessary for normal parathyroid dynamics, 32–36 ng/mL appears to be necessary for maximal intestinal calcium transport, and 30–40 ng/mL is the level that several randomized controlled trials have determined is necessary for fracture reduction.

“The good news is that vitamin D insufficiency is treatable,” Dr. Antoniucci said. “Replacement reestablishes vitamin D stores, and it improves bone mineral density because it allows optimal calcification of preexisting osteoid.”

Celiac Disease

Somewhere between 9% and 12% of patients with osteoporosis also have celiac disease. Conversely, about 50% of patients with celiac disease have a BMD that is two standard deviations or more under the mean. Among patients with celiac disease, those with a low BMD are more likely to have villous atrophy, an indication of more severe disease. The pathogenesis of bone disease in these patients is likely multifactorial, according to Dr. Antoniucci. They tend to have worse calcium absorption from the gut, especially before their disease is diagnosed, which can be many years in some patients. They also can have vitamin D deficiency from secondary hyperparathyroidism. Some women with celiac disease also have infertility and amenorrhea, both of which can lead to poor bone health.

At least one study has demonstrated that among patients with celiac disease, a strict gluten-free diet over the period of a year can improve bone mass in both men and women (Arch. Intern. Med. 2005;165:393–9). The authors of that study concluded that it's worth screening patients with unexplained osteoporosis for celiac disease. Dr. Antoniucci is not so sure that that's a good idea. “First of all, what exactly is 'unexplained osteoporosis'? And secondly, it might be a very expensive way to be treating the disease,” she said.

Androgen Deprivation Therapy

The longer a man is on this common therapy forprostate cancer, the greater his BMD loss and the greater his chance of fracture. After 10 years on androgen deprivation therapy, about 20% of men will have experienced a fracture, a risk fivefold greater than in age-matched controls. Slender white men appear to be at greatest risk, she said, noting that both pamidronate and zoledronate have been shown to prevent bone loss caused by androgen deprivation therapy.

Labs to Detect Secondary Osteoporosis

There is no consensus on whom to evaluate for secondary osteoporosis, said Dr. Antoniucci. However, “most people would agree that we should evaluate virtually all men with low T-scores, premenopausal women with low Z-scores or fragility fractures, and postmenopausal women,” she said.

Dr. Antoniucci said a standard laboratory work-up should include:

▸ Electrolyte levels.

▸ Renal and hepatic function.

▸ Complete blood count.

▸ 24-hour urine calcium excretion (which can provide important information if the result is very high or very low).

▸ 25-hydroxyvitamin D levels.

▸ Testosterone levels.

▸ Thyroid-stimulating hormone levels (in patients on thyroid hormone replacement).

Additional tests are dictated by the patient's history and physical exam and the physician's clinical judgment.

SAN FRANCISCO — Finding one possible cause of secondary osteoporosis does not mean there aren't other causes as well, Dr. Diana Antoniucci reported at a meeting on osteoporosis sponsored by the University of California, San Francisco.

“Having one secondary cause of osteoporosis does not preclude you from having another, so even if one contributor is obvious from the history, you can still consider laboratory testing,” said Dr. Antoniucci, of UCSF. (See sidebar for suggestions on which tests to order.) She listed four frequent causes of secondary osteoporosis for physicians to consider.

Glucocorticoid Use

This is the most common cause of drug-induced osteoporosis. In these patients, prevention is clearly the best strategy. All patients should be taking supplemental calcium and vitamin D, Dr. Antoniucci said, and if the patient has already been diagnosed with osteoporosis or is otherwise at high risk, the physician should measure bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). Clinical trials have shown that bisphosphonates halt bone loss and reduce fractures in patients taking glucocorticoids, and alendronate and risedronate are both approved for this indication. They should be considered for any patient on glucocorticoids with low BMD.

Vitamin D Deficiency

This deficiency is very common in the general population. Depending on the study population, the prevalence appears to range between 9% and 50%.

When severe, vitamin D deficiency is associated with osteomalacia, which is indistinguishable from low bone density on DXA. Less-severe vitamin D deficiency is associated with secondary hyperparathyroidism.

One difficulty in the assessment and treatment of vitamin D deficiency is that there is no general agreement as to what constitutes a sufficient level of 25-hydroxyvitamin D, Dr. Antoniucci noted. A level of 20 ng/mL appears to be necessary for normal parathyroid dynamics, 32–36 ng/mL appears to be necessary for maximal intestinal calcium transport, and 30–40 ng/mL is the level that several randomized controlled trials have determined is necessary for fracture reduction.

“The good news is that vitamin D insufficiency is treatable,” Dr. Antoniucci said. “Replacement reestablishes vitamin D stores, and it improves bone mineral density because it allows optimal calcification of preexisting osteoid.”

Celiac Disease

Somewhere between 9% and 12% of patients with osteoporosis also have celiac disease. Conversely, about 50% of patients with celiac disease have a BMD that is two standard deviations or more under the mean. Among patients with celiac disease, those with a low BMD are more likely to have villous atrophy, an indication of more severe disease. The pathogenesis of bone disease in these patients is likely multifactorial, according to Dr. Antoniucci. They tend to have worse calcium absorption from the gut, especially before their disease is diagnosed, which can be many years in some patients. They also can have vitamin D deficiency from secondary hyperparathyroidism. Some women with celiac disease also have infertility and amenorrhea, both of which can lead to poor bone health.

At least one study has demonstrated that among patients with celiac disease, a strict gluten-free diet over the period of a year can improve bone mass in both men and women (Arch. Intern. Med. 2005;165:393–9). The authors of that study concluded that it's worth screening patients with unexplained osteoporosis for celiac disease. Dr. Antoniucci is not so sure that that's a good idea. “First of all, what exactly is 'unexplained osteoporosis'? And secondly, it might be a very expensive way to be treating the disease,” she said.

Androgen Deprivation Therapy

The longer a man is on this common therapy forprostate cancer, the greater his BMD loss and the greater his chance of fracture. After 10 years on androgen deprivation therapy, about 20% of men will have experienced a fracture, a risk fivefold greater than in age-matched controls. Slender white men appear to be at greatest risk, she said, noting that both pamidronate and zoledronate have been shown to prevent bone loss caused by androgen deprivation therapy.

Labs to Detect Secondary Osteoporosis

There is no consensus on whom to evaluate for secondary osteoporosis, said Dr. Antoniucci. However, “most people would agree that we should evaluate virtually all men with low T-scores, premenopausal women with low Z-scores or fragility fractures, and postmenopausal women,” she said.

Dr. Antoniucci said a standard laboratory work-up should include:

▸ Electrolyte levels.

▸ Renal and hepatic function.

▸ Complete blood count.

▸ 24-hour urine calcium excretion (which can provide important information if the result is very high or very low).

▸ 25-hydroxyvitamin D levels.

▸ Testosterone levels.

▸ Thyroid-stimulating hormone levels (in patients on thyroid hormone replacement).

Additional tests are dictated by the patient's history and physical exam and the physician's clinical judgment.

BOSTON — To maintain skeletal health and reach optimal bone development, patients with childhood-onset growth hormone deficiency should continue therapy as they approach young adulthood, according to new treatment guidelines issued by The Endocrine Society.

“The mind set in the past has been that you treat these children until they stop growing,” Dr. Mark Molitch said at the society's annual meeting. “But the bones don't mature until the mid-20s, so they may still need the hormone as they transition into adulthood.”

In addition, he said, skeletal maturity may occur more slowly in patients with delayed onset of puberty or decreased gonadotropin secretion, so continuation of treatment is even more important for this population. Bone mineral density testing may provide additional valuable information for the decisions about continuing therapy.

The new guidelines, presented for the first time at the meeting, recommend retesting all children with idiopathic growth hormone deficiency as soon as possible after discontinuing the medication. Although many will have normal values, therapy should be quickly reinstituted for those who remain deficient.

The guidelines are based on 166 published studies examining the prevalence and diagnosis of growth hormone deficiency in adults, as well as treatment strategies and their long-term risks and benefits, said Dr. Molitch, chairman of the guidelines committee and professor of endocrinology at Northwestern University, Chicago.

The recommendations are aimed only at adults with clinically proven deficiency.

In the past, the insulin tolerance test was the favored diagnostic tool. However, this test carries an increased risk in patients with seizure disorders and cardiovascular disease, and requires close monitoring of even healthy patients. Recently, Dr. Molitch said, stimulation testing with growth hormone releasing hormone-arginine (GRHR-arginine) has gained favor. The test is less affected by age or obesity.

In a recent study of five different tests, including stimulation with GHRH-arginine and insulin tolerance, the stimulation test had 95% sensitivity and 91% specificity at the growth hormone cutoff level of 4.1 mcg/L; insulin testing was 96% sensitive and 92% specific at the cutoff level of 5.1 mcg/L.

Testing is indicated for adults with pituitary disease; surgery, trauma, or radiation in the pituitary area; or other pituitary deficiencies. Although children with idiopathic growth hormone deficiency should be retested as they approach adulthood, testing may be unnecessary for those with low insulinlike growth factor-1 and known defects, lesions, surgery or radiation of the hypothalamic-pituitary region, or a proven genetic defect of their capacity to secrete growth hormone. “This [combination] generally suffices to document continuing growth hormone deficiency,” the guidelines state. The evidence strongly supports individualized growth hormone dosing regimens. Generally, treatment should start low and be titrated upward based on clinical response, side effects, and IGF-1 levels.

Younger patients are likely to need higher doses, as are women, especially those on oral contraceptives, Dr. Molitch said. Patients aged 30–60 years can usually start at 300 mcg/day; dosing should be increased by 100–200 mcg/day every 1–2 months, with a therapeutic target of an IGF-1 level in the upper half of the normal range.

Older patients should be started on 100–200 mcg/day, while those younger than 30 years may benefit from initially higher doses (400–500 mcg/day).

Although no studies have linked growth hormone therapy with malignancies, the guidelines recommend against using the hormone in anyone with an active cancer. There is no evidence that treatment affects the recurrence of pituitary tumors. Patients with diabetes may need adjustments to their diabetes medications when on growth hormone. The side effects of growth hormone therapy are usually dose-related and can be alleviated by adjusting the medication. The most common are related to fluid retention. These effects occur in up to 18% of patients and include paresthesias, joint stiffness, peripheral edema, arthralgia, and myalgia. Increased blood pressure is sometimes seen, but can be avoided with appropriate dosing.

Therapy offers significant benefits, including a decrease in fat mass and its attendant risk reductions of improved lipid levels and decreased insulin resistance. The modest increases in muscle mass improve exercise tolerance, which in turn has beneficial effects on blood pressure and cardiac function. Patients with childhood-onset growth hormone deficiency also may experience improvements in left ventricular muscle mass and end diastolic volume, as well as stroke volume. Therapy also benefits bone health with both anabolic and antiresorptive effects.

While no studies have confirmed a mortality benefit with growth hormone therapy, some do suggest that mortality is increased in those with hypopituitarism. It is not proved that growth hormone decreases it.

BOSTON — To maintain skeletal health and reach optimal bone development, patients with childhood-onset growth hormone deficiency should continue therapy as they approach young adulthood, according to new treatment guidelines issued by The Endocrine Society.

“The mind set in the past has been that you treat these children until they stop growing,” Dr. Mark Molitch said at the society's annual meeting. “But the bones don't mature until the mid-20s, so they may still need the hormone as they transition into adulthood.”

In addition, he said, skeletal maturity may occur more slowly in patients with delayed onset of puberty or decreased gonadotropin secretion, so continuation of treatment is even more important for this population. Bone mineral density testing may provide additional valuable information for the decisions about continuing therapy.

The new guidelines, presented for the first time at the meeting, recommend retesting all children with idiopathic growth hormone deficiency as soon as possible after discontinuing the medication. Although many will have normal values, therapy should be quickly reinstituted for those who remain deficient.

The guidelines are based on 166 published studies examining the prevalence and diagnosis of growth hormone deficiency in adults, as well as treatment strategies and their long-term risks and benefits, said Dr. Molitch, chairman of the guidelines committee and professor of endocrinology at Northwestern University, Chicago.

The recommendations are aimed only at adults with clinically proven deficiency.

In the past, the insulin tolerance test was the favored diagnostic tool. However, this test carries an increased risk in patients with seizure disorders and cardiovascular disease, and requires close monitoring of even healthy patients. Recently, Dr. Molitch said, stimulation testing with growth hormone releasing hormone-arginine (GRHR-arginine) has gained favor. The test is less affected by age or obesity.

In a recent study of five different tests, including stimulation with GHRH-arginine and insulin tolerance, the stimulation test had 95% sensitivity and 91% specificity at the growth hormone cutoff level of 4.1 mcg/L; insulin testing was 96% sensitive and 92% specific at the cutoff level of 5.1 mcg/L.

Testing is indicated for adults with pituitary disease; surgery, trauma, or radiation in the pituitary area; or other pituitary deficiencies. Although children with idiopathic growth hormone deficiency should be retested as they approach adulthood, testing may be unnecessary for those with low insulinlike growth factor-1 and known defects, lesions, surgery or radiation of the hypothalamic-pituitary region, or a proven genetic defect of their capacity to secrete growth hormone. “This [combination] generally suffices to document continuing growth hormone deficiency,” the guidelines state. The evidence strongly supports individualized growth hormone dosing regimens. Generally, treatment should start low and be titrated upward based on clinical response, side effects, and IGF-1 levels.

Younger patients are likely to need higher doses, as are women, especially those on oral contraceptives, Dr. Molitch said. Patients aged 30–60 years can usually start at 300 mcg/day; dosing should be increased by 100–200 mcg/day every 1–2 months, with a therapeutic target of an IGF-1 level in the upper half of the normal range.

Older patients should be started on 100–200 mcg/day, while those younger than 30 years may benefit from initially higher doses (400–500 mcg/day).

Although no studies have linked growth hormone therapy with malignancies, the guidelines recommend against using the hormone in anyone with an active cancer. There is no evidence that treatment affects the recurrence of pituitary tumors. Patients with diabetes may need adjustments to their diabetes medications when on growth hormone. The side effects of growth hormone therapy are usually dose-related and can be alleviated by adjusting the medication. The most common are related to fluid retention. These effects occur in up to 18% of patients and include paresthesias, joint stiffness, peripheral edema, arthralgia, and myalgia. Increased blood pressure is sometimes seen, but can be avoided with appropriate dosing.

Therapy offers significant benefits, including a decrease in fat mass and its attendant risk reductions of improved lipid levels and decreased insulin resistance. The modest increases in muscle mass improve exercise tolerance, which in turn has beneficial effects on blood pressure and cardiac function. Patients with childhood-onset growth hormone deficiency also may experience improvements in left ventricular muscle mass and end diastolic volume, as well as stroke volume. Therapy also benefits bone health with both anabolic and antiresorptive effects.

While no studies have confirmed a mortality benefit with growth hormone therapy, some do suggest that mortality is increased in those with hypopituitarism. It is not proved that growth hormone decreases it.

BOSTON — To maintain skeletal health and reach optimal bone development, patients with childhood-onset growth hormone deficiency should continue therapy as they approach young adulthood, according to new treatment guidelines issued by The Endocrine Society.

“The mind set in the past has been that you treat these children until they stop growing,” Dr. Mark Molitch said at the society's annual meeting. “But the bones don't mature until the mid-20s, so they may still need the hormone as they transition into adulthood.”

In addition, he said, skeletal maturity may occur more slowly in patients with delayed onset of puberty or decreased gonadotropin secretion, so continuation of treatment is even more important for this population. Bone mineral density testing may provide additional valuable information for the decisions about continuing therapy.

The new guidelines, presented for the first time at the meeting, recommend retesting all children with idiopathic growth hormone deficiency as soon as possible after discontinuing the medication. Although many will have normal values, therapy should be quickly reinstituted for those who remain deficient.

The guidelines are based on 166 published studies examining the prevalence and diagnosis of growth hormone deficiency in adults, as well as treatment strategies and their long-term risks and benefits, said Dr. Molitch, chairman of the guidelines committee and professor of endocrinology at Northwestern University, Chicago.

The recommendations are aimed only at adults with clinically proven deficiency.

In the past, the insulin tolerance test was the favored diagnostic tool. However, this test carries an increased risk in patients with seizure disorders and cardiovascular disease, and requires close monitoring of even healthy patients. Recently, Dr. Molitch said, stimulation testing with growth hormone releasing hormone-arginine (GRHR-arginine) has gained favor. The test is less affected by age or obesity.

In a recent study of five different tests, including stimulation with GHRH-arginine and insulin tolerance, the stimulation test had 95% sensitivity and 91% specificity at the growth hormone cutoff level of 4.1 mcg/L; insulin testing was 96% sensitive and 92% specific at the cutoff level of 5.1 mcg/L.

Testing is indicated for adults with pituitary disease; surgery, trauma, or radiation in the pituitary area; or other pituitary deficiencies. Although children with idiopathic growth hormone deficiency should be retested as they approach adulthood, testing may be unnecessary for those with low insulinlike growth factor-1 and known defects, lesions, surgery or radiation of the hypothalamic-pituitary region, or a proven genetic defect of their capacity to secrete growth hormone. “This [combination] generally suffices to document continuing growth hormone deficiency,” the guidelines state. The evidence strongly supports individualized growth hormone dosing regimens. Generally, treatment should start low and be titrated upward based on clinical response, side effects, and IGF-1 levels.

Younger patients are likely to need higher doses, as are women, especially those on oral contraceptives, Dr. Molitch said. Patients aged 30–60 years can usually start at 300 mcg/day; dosing should be increased by 100–200 mcg/day every 1–2 months, with a therapeutic target of an IGF-1 level in the upper half of the normal range.

Older patients should be started on 100–200 mcg/day, while those younger than 30 years may benefit from initially higher doses (400–500 mcg/day).

Although no studies have linked growth hormone therapy with malignancies, the guidelines recommend against using the hormone in anyone with an active cancer. There is no evidence that treatment affects the recurrence of pituitary tumors. Patients with diabetes may need adjustments to their diabetes medications when on growth hormone. The side effects of growth hormone therapy are usually dose-related and can be alleviated by adjusting the medication. The most common are related to fluid retention. These effects occur in up to 18% of patients and include paresthesias, joint stiffness, peripheral edema, arthralgia, and myalgia. Increased blood pressure is sometimes seen, but can be avoided with appropriate dosing.

Therapy offers significant benefits, including a decrease in fat mass and its attendant risk reductions of improved lipid levels and decreased insulin resistance. The modest increases in muscle mass improve exercise tolerance, which in turn has beneficial effects on blood pressure and cardiac function. Patients with childhood-onset growth hormone deficiency also may experience improvements in left ventricular muscle mass and end diastolic volume, as well as stroke volume. Therapy also benefits bone health with both anabolic and antiresorptive effects.

While no studies have confirmed a mortality benefit with growth hormone therapy, some do suggest that mortality is increased in those with hypopituitarism. It is not proved that growth hormone decreases it.

Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.

In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.

Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).

In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”

“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).

The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).

A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.

A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.

The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.

Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.

In both groups, the mean age was 68 years.

There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).

Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.

The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.

The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”

There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.

The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.

The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.

However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.

Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.

The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.

In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.

Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.

In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.

Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).

In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”

“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).

The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).

A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.

A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.

The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.

Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.

In both groups, the mean age was 68 years.

There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).

Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.

The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.

The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”

There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.

The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.

The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.

However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.

Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.

The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.

In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.

Raloxifene did not significantly increase the risk of coronary events in women with coronary heart disease or those at high risk for the disease in a randomized study of more than 10,000 postmenopausal women.

In addition, treatment with raloxifene for a median of 5 years decreased the risk of invasive breast cancer and vertebral fractures but increased the risks of venous thromboembolic events and fatal stroke, study investigators reported.

Dr. Elizabeth Barrett-Connor of the University of California, San Diego, and her colleagues concluded that when considering the use of raloxifene in a postmenopausal woman, clinicians should “weigh the benefits and risks against the availability of alternative interventions” (N. Engl. J. Med. 2006;355:125–37).

In an accompanying editorial, Marcia L. Stefanick, Ph.D., agreed with that conclusion, but noted that, for postmenopausal women similar to those in the study who have or are at increased risk of coronary heart disease (CHD), the modest benefits offered by raloxifene as a breast cancer prophylaxis “do not seem to justify the risks.”

“For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns,” said Dr. Stefanick of Stanford (Calif.) University (N. Engl. J. Med. 2006;355:190–2).

The Raloxifene Use for the Heart study, an international, multicenter, randomized, double-blind, placebo-controlled trial, was conducted to determine of the effect of the drug on clinical coronary events. The study was supported by Eli Lilly, maker of raloxifene (marketed as Evista).

A total of 10,101 postmenopausal women were enrolled from June 1998 through August 2000. The participants were at least 1 year post menopause and had established CHD or were at increased risk for CHD.

A total of 5,057 participants were randomized to receive 60 mg of oral raloxifene daily, and 5,044 were randomized to placebo.

The median duration of follow-up was 5.6 years; 80% of those in the raloxifene group and 79% in the placebo group completed the study.

Both groups had similar baseline characteristics, “except that the raloxifene group had a slightly higher cardiovascular risk score and a higher proportion of women reporting coronary artery bypass grafting,” the researchers said.

In both groups, the mean age was 68 years.

There was no significant difference between the raloxifene and placebo groups in the study's combined coronary end point of death from coronary causes, nonfatal myocardial infarction, or hospitalization for an acute coronary syndrome other than myocardial infarction (533 events vs. 553 events, hazard ratio of 0.95).

Raloxifene, a nonsteroidal selective estrogen-receptor modulator, reduced the incidence of invasive breast cancer (hazard ratio, 0.56), another primary outcome in the study.

The researchers attributed this finding “to a reduction in estrogen-receptor-positive invasive breast cancer.

The absolute risk reduction per 1,000 women treated with raloxifene for 1 year was 1.2 cases of invasive breast cancer and 1.2 cases of estrogen-receptor-positive invasive breast cancer.”

There was no significant difference between the two groups in the incidence of estrogen-receptor-negative invasive breast cancer.

The overall stroke rate, a secondary outcome, did not differ between groups, but the incidence of fatal stroke was 49% higher in the raloxifene group, compared with the placebo group (59 events vs. 39 events); the absolute risk increase was 0.7 per 1,000 woman-years.

The incidence of venous thromboembolic events was 44% higher in the raloxifene group, compared with placebo (103 events vs. 71 events); the absolute risk increase was 1.2 per 1,000 woman-years.

However, the raloxifene group also showed a 33% lower incidence of all breast cancers, with an absolute risk reduction of 0.9 per 1,000 woman-years.

Raloxifene users also had a 35% lower incidence of clinical vertebral fractures; their absolute risk reduction was 1.3 per 1,000 woman-years.

The raloxifene group also had a lower rate of death from noncardiovascular causes (188 events vs. 231 events in the placebo group), but there was no significant difference between groups in death from any cause or overall death from cardiovascular causes.

In addition, participants in the placebo group showed an increase of 3.6% in low-density lipoprotein (LDL) cholesterol and a 0.9% increase in high-density lipoprotein (HDL) cholesterol, compared with a 4.4% decrease in LDL cholesterol and a 2.3% increase in HDL cholesterol for raloxifene users.

GLASGOW, SCOTLAND — Soy products and dietary supplements containing a high level of flavonoids may be alternatives to chemoprevention of osteoporosis and prostate cancer, so long as consumption is moderated to limit the potential for side effects, investigators said at the 8th European Congress of Endocrinology.

Much of the evidence supporting the benefits of dietary soy comes from epidemiologic studies and analyses of disease patterns in Asians who change their diets after migrating to the West, according to Eva Lydeking-Olsen, a nurse practitioner and nutritionist with the Institute for Optimum Nutrition in Copenhagen.

When it comes to bone protection, epidemiologic studies and double-blinded placebo-controlled trials of soy lasting at least 6 months have shown mixed results. Four of 12 such studies have shown no benefits, as measured by dual-energy x-ray densitometry scans of bone mineral density (BMD), while eight have, said Ms. Lydeking-Olsen.

The eight showing a bone-protective effect focused on at-risk groups, so it was likely that continuing loss of bone mass in the control group affected the outcomes of the study, she said.

Consumption of 50–90 mg of isoflavones appears to have a beneficial effect, roughly the same as drinking two glasses of soy milk per day, she said.

“In the case of soy foods it is advisable to ask the manufacturer about the amount of isoflavones in specific brands of soy milk and soy yogurt, and also use foods such as natural, roasted soy flakes—on muesli, mixed in hot cereal or sprinkled over the salad—or soy nuts as a snack, as very little [isoflavone is] lost in those natural products,” she said in an interview.

Another expert, however, warned that the there is evidence that behavior of isoflavones could potentially have the same negative effects as estrogen, such as stimulating growth of uterine and breast tissues, leading to tumors.

“There is good evidence that lifelong intake of these isoflavones can be beneficial,” said Dr. Wolfgang Wuttke, professor of clinical and experimental endocrinology at the University of Göttingen. “But these are prepubertal effects.

“The evidence is so controversial that the [Food and Drug Administration] … would never allow sale of these substances as a drug,” said Dr. Wuttke “Why should I recommend substances which I am not sure are safe and might be useless?”

But when it comes to prostate cancer, Dr. Wuttke said that he believes there may be benefits for older men with increased isoflavone consumption.

Among the most studied of the isoflavones influencing prostate health is genistein, which may slow with the growth of prostate cells by influencing the hormone-metabolizing enzymes and reducing the sensitivity of the primary targets of androgen hormones such as the androgen receptor, said Dr. Helmut Klocker, a specialist in urology at Innsbruck (Austria) University Hospital.

Unlike with osteoporosis and soy, Dr. Klocker said there are no double-blinded placebo-controlled studies demonstrating the preventive effect of genistein.

“The problem with these [studies] is they would have to be performed over many years,” he said in an interview. “To my knowledge, it is not clear if there is a beneficial effect at any [specific] time in life. There is also some evidence that exposure to genistein and related substances is most efficient during growing up and puberty, and even during embryogenesis. You can imagine that it is almost impossible to investigate this in controlled trials.”

In a phase II trial sponsored by the National Cancer Institute, scientists are recruiting patients to test both the effectiveness and potential toxicity of genistein among men with stage I and stage II prostate cancer.

The trial plans to randomize 88 patients undergoing radical prostatectomy into two groups. One group will receive oral genistein once daily for 1–2 months, undergo the prostatectomy, and then continue the genistein regimen for 1–2 months afterward. The other group will undergo the prostatectomy first, and begin a 3-month genistein regimen 1 month after the surgery. The trial will test the reduction in prostate-specific angigen-positive cells in the operative field and quality of life at baseline and 1 and 3 months after surgery, Dr. Klocker said.

GLASGOW, SCOTLAND — Soy products and dietary supplements containing a high level of flavonoids may be alternatives to chemoprevention of osteoporosis and prostate cancer, so long as consumption is moderated to limit the potential for side effects, investigators said at the 8th European Congress of Endocrinology.

Much of the evidence supporting the benefits of dietary soy comes from epidemiologic studies and analyses of disease patterns in Asians who change their diets after migrating to the West, according to Eva Lydeking-Olsen, a nurse practitioner and nutritionist with the Institute for Optimum Nutrition in Copenhagen.

When it comes to bone protection, epidemiologic studies and double-blinded placebo-controlled trials of soy lasting at least 6 months have shown mixed results. Four of 12 such studies have shown no benefits, as measured by dual-energy x-ray densitometry scans of bone mineral density (BMD), while eight have, said Ms. Lydeking-Olsen.

The eight showing a bone-protective effect focused on at-risk groups, so it was likely that continuing loss of bone mass in the control group affected the outcomes of the study, she said.

Consumption of 50–90 mg of isoflavones appears to have a beneficial effect, roughly the same as drinking two glasses of soy milk per day, she said.

“In the case of soy foods it is advisable to ask the manufacturer about the amount of isoflavones in specific brands of soy milk and soy yogurt, and also use foods such as natural, roasted soy flakes—on muesli, mixed in hot cereal or sprinkled over the salad—or soy nuts as a snack, as very little [isoflavone is] lost in those natural products,” she said in an interview.

Another expert, however, warned that the there is evidence that behavior of isoflavones could potentially have the same negative effects as estrogen, such as stimulating growth of uterine and breast tissues, leading to tumors.

“There is good evidence that lifelong intake of these isoflavones can be beneficial,” said Dr. Wolfgang Wuttke, professor of clinical and experimental endocrinology at the University of Göttingen. “But these are prepubertal effects.

“The evidence is so controversial that the [Food and Drug Administration] … would never allow sale of these substances as a drug,” said Dr. Wuttke “Why should I recommend substances which I am not sure are safe and might be useless?”

But when it comes to prostate cancer, Dr. Wuttke said that he believes there may be benefits for older men with increased isoflavone consumption.

Among the most studied of the isoflavones influencing prostate health is genistein, which may slow with the growth of prostate cells by influencing the hormone-metabolizing enzymes and reducing the sensitivity of the primary targets of androgen hormones such as the androgen receptor, said Dr. Helmut Klocker, a specialist in urology at Innsbruck (Austria) University Hospital.

Unlike with osteoporosis and soy, Dr. Klocker said there are no double-blinded placebo-controlled studies demonstrating the preventive effect of genistein.

“The problem with these [studies] is they would have to be performed over many years,” he said in an interview. “To my knowledge, it is not clear if there is a beneficial effect at any [specific] time in life. There is also some evidence that exposure to genistein and related substances is most efficient during growing up and puberty, and even during embryogenesis. You can imagine that it is almost impossible to investigate this in controlled trials.”

In a phase II trial sponsored by the National Cancer Institute, scientists are recruiting patients to test both the effectiveness and potential toxicity of genistein among men with stage I and stage II prostate cancer.

The trial plans to randomize 88 patients undergoing radical prostatectomy into two groups. One group will receive oral genistein once daily for 1–2 months, undergo the prostatectomy, and then continue the genistein regimen for 1–2 months afterward. The other group will undergo the prostatectomy first, and begin a 3-month genistein regimen 1 month after the surgery. The trial will test the reduction in prostate-specific angigen-positive cells in the operative field and quality of life at baseline and 1 and 3 months after surgery, Dr. Klocker said.

GLASGOW, SCOTLAND — Soy products and dietary supplements containing a high level of flavonoids may be alternatives to chemoprevention of osteoporosis and prostate cancer, so long as consumption is moderated to limit the potential for side effects, investigators said at the 8th European Congress of Endocrinology.

Much of the evidence supporting the benefits of dietary soy comes from epidemiologic studies and analyses of disease patterns in Asians who change their diets after migrating to the West, according to Eva Lydeking-Olsen, a nurse practitioner and nutritionist with the Institute for Optimum Nutrition in Copenhagen.

When it comes to bone protection, epidemiologic studies and double-blinded placebo-controlled trials of soy lasting at least 6 months have shown mixed results. Four of 12 such studies have shown no benefits, as measured by dual-energy x-ray densitometry scans of bone mineral density (BMD), while eight have, said Ms. Lydeking-Olsen.

The eight showing a bone-protective effect focused on at-risk groups, so it was likely that continuing loss of bone mass in the control group affected the outcomes of the study, she said.

Consumption of 50–90 mg of isoflavones appears to have a beneficial effect, roughly the same as drinking two glasses of soy milk per day, she said.

“In the case of soy foods it is advisable to ask the manufacturer about the amount of isoflavones in specific brands of soy milk and soy yogurt, and also use foods such as natural, roasted soy flakes—on muesli, mixed in hot cereal or sprinkled over the salad—or soy nuts as a snack, as very little [isoflavone is] lost in those natural products,” she said in an interview.

Another expert, however, warned that the there is evidence that behavior of isoflavones could potentially have the same negative effects as estrogen, such as stimulating growth of uterine and breast tissues, leading to tumors.

“There is good evidence that lifelong intake of these isoflavones can be beneficial,” said Dr. Wolfgang Wuttke, professor of clinical and experimental endocrinology at the University of Göttingen. “But these are prepubertal effects.

“The evidence is so controversial that the [Food and Drug Administration] … would never allow sale of these substances as a drug,” said Dr. Wuttke “Why should I recommend substances which I am not sure are safe and might be useless?”

But when it comes to prostate cancer, Dr. Wuttke said that he believes there may be benefits for older men with increased isoflavone consumption.

Among the most studied of the isoflavones influencing prostate health is genistein, which may slow with the growth of prostate cells by influencing the hormone-metabolizing enzymes and reducing the sensitivity of the primary targets of androgen hormones such as the androgen receptor, said Dr. Helmut Klocker, a specialist in urology at Innsbruck (Austria) University Hospital.

Unlike with osteoporosis and soy, Dr. Klocker said there are no double-blinded placebo-controlled studies demonstrating the preventive effect of genistein.

“The problem with these [studies] is they would have to be performed over many years,” he said in an interview. “To my knowledge, it is not clear if there is a beneficial effect at any [specific] time in life. There is also some evidence that exposure to genistein and related substances is most efficient during growing up and puberty, and even during embryogenesis. You can imagine that it is almost impossible to investigate this in controlled trials.”

In a phase II trial sponsored by the National Cancer Institute, scientists are recruiting patients to test both the effectiveness and potential toxicity of genistein among men with stage I and stage II prostate cancer.

The trial plans to randomize 88 patients undergoing radical prostatectomy into two groups. One group will receive oral genistein once daily for 1–2 months, undergo the prostatectomy, and then continue the genistein regimen for 1–2 months afterward. The other group will undergo the prostatectomy first, and begin a 3-month genistein regimen 1 month after the surgery. The trial will test the reduction in prostate-specific angigen-positive cells in the operative field and quality of life at baseline and 1 and 3 months after surgery, Dr. Klocker said.

CHICAGO — Endocrinologists are “behind the curve” when it comes to treating osteoporosis, Dr. Nelson B. Watts said at the annual meeting of the American Association of Clinical Endocrinologists.

“There is roughly the same number of rheumatologists as endocrinologists in the United States,” said Dr. Watts, director of the osteoporosis and bone health program at the University of Cincinnati. “In academic centers, endocrinologists are often the 'boneheads,' but in clinical practice, rheumatologists compared with endocrinologists are twice as fast as we are in taking up ownership of densitometry or prescribing osteoporosis drugs.”

Osteoporosis groups are “in pretty good agreement” on several of the guidelines for treatment of the disorder, according to Dr. Watts, who consults for and receives grants from a number of pharmaceutical companies. “The National Osteoporosis Foundation, AACE, and the North American Menopause Society are all in agreement that patients with T scores of −1.5 or above are rarely candidates for pharmacologic treatment,” he said. “And they all agree that those with T scores of −2.5 or below should be treated even in the absence of risk factors. It's that zone in between where there's disagreement.”

The National Osteoporosis Foundation says that if the patient has risk factors for osteoporosis—such as previous fractures and advanced age—and her T score is between −1.5 and −2, the physician should go ahead and treat the patient. The doctor also should treat the patient if the T score is −2 or below, even in the absence of risk factors, the foundation says. AACE suggests treating patients whose T scores are between −1.5 and −2.5 only if risk factors are present, while the North American Menopause Society advocates no treatment if the T score is between −1.5 and −2 but suggests that patients between −2 and −2.5 should be treated if risk factors are present, Dr. Watts said.

How should physicians handle this “gray zone”? The problem with treating only patients with T scores of −2.5 or below “is that there are patients above −2.5 who actually have a fairly high 10-year probability of fracture, and unless we're smart enough to know by intuition what the right risk factors are, many of those patients aren't being treated,” said Dr. Watts.

The most recent thinking is toward moving away from T scores to something called “absolute fracture risk” or “absolute fracture probability,” he continued. “This will consider bone density, but in countries that have little or no access to bone density [measurement], this will be based solely on clinical risk factors.” In addition to age and history of fractures, other risk factors that are likely to be included are corticosteroid use, cigarette smoking, alcohol use, and rheumatoid arthritis. Also, patients who self-rate their health as poor or fair are almost twice as likely to fracture as are those who say their health is good or excellent.

Dr. Watts offered these tips on managing patients with a high fracture risk:

▸ Consider hip protectors and assistive devices. There are conflicting data on whether using hip protectors reduces the risk of fracture. But physicians who are interested in recommending them can easily find them on the Internet.

▸ Be judicious with pharmacologic therapy. Dr. Watts said bone drugs such as alendronate, raloxifene, ibandronate, risedronate, and calcitonin are only shown to reduce the risk of fracture in patients with low bone density, and are not appropriate if the risk is due to poor eyesight, poor hearing, poor balance, and muscle weakness.

▸ Advocate exercise. “Weight-bearing exercise is important,” he said. “I recommend patients walk for 30–40 minutes a session, 3–4 sessions per week.”

▸ Remember that when it comes to calcium, more is not always better. The optimal calcium intake is 1,200 mg per day for adults aged 50 and older, he noted. The average adult gets only half of what is needed from the diet, so most people do need a supplement; 700–1,000 mg per day should be adequate. But many people take too much. “I see patients who are taking in 3,000–3,500 mg of calcium per day. So I spend a fair amount of time telling patients to take less calcium by way of supplements, rather than more.”

▸ Consider recommending vitamin D. “An adequate 25-hydroxyvitamin D level is 30 ng/mL or more,” he said. “Many patients require 1,000–2,000 IU of vitamin D per day to achieve this level.”

CHICAGO — Endocrinologists are “behind the curve” when it comes to treating osteoporosis, Dr. Nelson B. Watts said at the annual meeting of the American Association of Clinical Endocrinologists.

“There is roughly the same number of rheumatologists as endocrinologists in the United States,” said Dr. Watts, director of the osteoporosis and bone health program at the University of Cincinnati. “In academic centers, endocrinologists are often the 'boneheads,' but in clinical practice, rheumatologists compared with endocrinologists are twice as fast as we are in taking up ownership of densitometry or prescribing osteoporosis drugs.”

Osteoporosis groups are “in pretty good agreement” on several of the guidelines for treatment of the disorder, according to Dr. Watts, who consults for and receives grants from a number of pharmaceutical companies. “The National Osteoporosis Foundation, AACE, and the North American Menopause Society are all in agreement that patients with T scores of −1.5 or above are rarely candidates for pharmacologic treatment,” he said. “And they all agree that those with T scores of −2.5 or below should be treated even in the absence of risk factors. It's that zone in between where there's disagreement.”

The National Osteoporosis Foundation says that if the patient has risk factors for osteoporosis—such as previous fractures and advanced age—and her T score is between −1.5 and −2, the physician should go ahead and treat the patient. The doctor also should treat the patient if the T score is −2 or below, even in the absence of risk factors, the foundation says. AACE suggests treating patients whose T scores are between −1.5 and −2.5 only if risk factors are present, while the North American Menopause Society advocates no treatment if the T score is between −1.5 and −2 but suggests that patients between −2 and −2.5 should be treated if risk factors are present, Dr. Watts said.

How should physicians handle this “gray zone”? The problem with treating only patients with T scores of −2.5 or below “is that there are patients above −2.5 who actually have a fairly high 10-year probability of fracture, and unless we're smart enough to know by intuition what the right risk factors are, many of those patients aren't being treated,” said Dr. Watts.

The most recent thinking is toward moving away from T scores to something called “absolute fracture risk” or “absolute fracture probability,” he continued. “This will consider bone density, but in countries that have little or no access to bone density [measurement], this will be based solely on clinical risk factors.” In addition to age and history of fractures, other risk factors that are likely to be included are corticosteroid use, cigarette smoking, alcohol use, and rheumatoid arthritis. Also, patients who self-rate their health as poor or fair are almost twice as likely to fracture as are those who say their health is good or excellent.

Dr. Watts offered these tips on managing patients with a high fracture risk:

▸ Consider hip protectors and assistive devices. There are conflicting data on whether using hip protectors reduces the risk of fracture. But physicians who are interested in recommending them can easily find them on the Internet.

▸ Be judicious with pharmacologic therapy. Dr. Watts said bone drugs such as alendronate, raloxifene, ibandronate, risedronate, and calcitonin are only shown to reduce the risk of fracture in patients with low bone density, and are not appropriate if the risk is due to poor eyesight, poor hearing, poor balance, and muscle weakness.

▸ Advocate exercise. “Weight-bearing exercise is important,” he said. “I recommend patients walk for 30–40 minutes a session, 3–4 sessions per week.”

▸ Remember that when it comes to calcium, more is not always better. The optimal calcium intake is 1,200 mg per day for adults aged 50 and older, he noted. The average adult gets only half of what is needed from the diet, so most people do need a supplement; 700–1,000 mg per day should be adequate. But many people take too much. “I see patients who are taking in 3,000–3,500 mg of calcium per day. So I spend a fair amount of time telling patients to take less calcium by way of supplements, rather than more.”

▸ Consider recommending vitamin D. “An adequate 25-hydroxyvitamin D level is 30 ng/mL or more,” he said. “Many patients require 1,000–2,000 IU of vitamin D per day to achieve this level.”

CHICAGO — Endocrinologists are “behind the curve” when it comes to treating osteoporosis, Dr. Nelson B. Watts said at the annual meeting of the American Association of Clinical Endocrinologists.

“There is roughly the same number of rheumatologists as endocrinologists in the United States,” said Dr. Watts, director of the osteoporosis and bone health program at the University of Cincinnati. “In academic centers, endocrinologists are often the 'boneheads,' but in clinical practice, rheumatologists compared with endocrinologists are twice as fast as we are in taking up ownership of densitometry or prescribing osteoporosis drugs.”

Osteoporosis groups are “in pretty good agreement” on several of the guidelines for treatment of the disorder, according to Dr. Watts, who consults for and receives grants from a number of pharmaceutical companies. “The National Osteoporosis Foundation, AACE, and the North American Menopause Society are all in agreement that patients with T scores of −1.5 or above are rarely candidates for pharmacologic treatment,” he said. “And they all agree that those with T scores of −2.5 or below should be treated even in the absence of risk factors. It's that zone in between where there's disagreement.”

The National Osteoporosis Foundation says that if the patient has risk factors for osteoporosis—such as previous fractures and advanced age—and her T score is between −1.5 and −2, the physician should go ahead and treat the patient. The doctor also should treat the patient if the T score is −2 or below, even in the absence of risk factors, the foundation says. AACE suggests treating patients whose T scores are between −1.5 and −2.5 only if risk factors are present, while the North American Menopause Society advocates no treatment if the T score is between −1.5 and −2 but suggests that patients between −2 and −2.5 should be treated if risk factors are present, Dr. Watts said.

How should physicians handle this “gray zone”? The problem with treating only patients with T scores of −2.5 or below “is that there are patients above −2.5 who actually have a fairly high 10-year probability of fracture, and unless we're smart enough to know by intuition what the right risk factors are, many of those patients aren't being treated,” said Dr. Watts.

The most recent thinking is toward moving away from T scores to something called “absolute fracture risk” or “absolute fracture probability,” he continued. “This will consider bone density, but in countries that have little or no access to bone density [measurement], this will be based solely on clinical risk factors.” In addition to age and history of fractures, other risk factors that are likely to be included are corticosteroid use, cigarette smoking, alcohol use, and rheumatoid arthritis. Also, patients who self-rate their health as poor or fair are almost twice as likely to fracture as are those who say their health is good or excellent.

Dr. Watts offered these tips on managing patients with a high fracture risk:

▸ Consider hip protectors and assistive devices. There are conflicting data on whether using hip protectors reduces the risk of fracture. But physicians who are interested in recommending them can easily find them on the Internet.

▸ Be judicious with pharmacologic therapy. Dr. Watts said bone drugs such as alendronate, raloxifene, ibandronate, risedronate, and calcitonin are only shown to reduce the risk of fracture in patients with low bone density, and are not appropriate if the risk is due to poor eyesight, poor hearing, poor balance, and muscle weakness.

▸ Advocate exercise. “Weight-bearing exercise is important,” he said. “I recommend patients walk for 30–40 minutes a session, 3–4 sessions per week.”

▸ Remember that when it comes to calcium, more is not always better. The optimal calcium intake is 1,200 mg per day for adults aged 50 and older, he noted. The average adult gets only half of what is needed from the diet, so most people do need a supplement; 700–1,000 mg per day should be adequate. But many people take too much. “I see patients who are taking in 3,000–3,500 mg of calcium per day. So I spend a fair amount of time telling patients to take less calcium by way of supplements, rather than more.”

▸ Consider recommending vitamin D. “An adequate 25-hydroxyvitamin D level is 30 ng/mL or more,” he said. “Many patients require 1,000–2,000 IU of vitamin D per day to achieve this level.”

ATLANTA — A retrospective analysis of data from nearly 4,000 patients treated with intravenous bisphosphonates suggests that osteonecrosis of the jaw in patients with metastatic cancer is an important but rare event in these patients, Dr. Ana O. Hoff reported in a poster at the annual meeting of the American Society of Clinical Oncology.

Reports of an association between bisphosphonate treatment and osteonecrosis of the jaw (ONJ) in patients with metastatic bone disease prompted this study examining the frequency of and risk factors for ONJ, explained Dr. Hoff of the University of Texas M.D. Anderson Cancer Center, Houston.

The cohort studied included patients treated from September 1996 to February 2004. The most common diagnoses were breast cancer and multiple myeloma, and the indications for intravenous bisphosphonate treatment included metastatic bone disease, hypercalcemia, and osteoporosis.

ONJ, which developed in 29 patients (0.73% overall, including about 1% of breast cancer patients and 2% of multiple myeloma patients), was defined as exposed nonhealing bone of at least 3 months' duration.

Mean cumulative doses of the bisphosphonates used (pamidronate and zoledronate) were significantly higher, and duration of disease and follow-up were significantly longer, in ONJ patients than in those who didn't develop ONJ.

Dental extractions, estrogen-receptor-positive tumors, and treatment with pamidronate and zoledronate were shown to be significant risk factors for ONJ in breast cancer patients. In multiple myeloma patients, significant risk factors were dental extractions, periodontal disease, and osteoporosis.

About 70% of ONJ patients reported no pain with bone exposure, Dr. Hoff noted.

Management of ONJ included aggressive oral hygiene, oral rinses, debridement of necrotic bone, and antibiotic therapy. Of 15 ONJ patients followed longer than 6 months, 1 healed, 1 improved, 1 remained stable, and 9 experienced disease progression.

Race May Be ONJ Risk

White cancer patients on intravenous bisphosphonate therapy for bone metastases may be at higher risk for osteonecrosis of the jaw, Dr. Tamer Aiti reported in a poster at the meeting.

A retrospective study by Dr. Aiti and colleagues at John H. Stroger Jr. Cook County Hospital, Chicago, found that 6 of 161 patients with metastatic breast cancer developed this rare complication in the mandible bone. Five of the six patients were white. Yet whites accounted for less than a third of the population reviewed. All but 29 patients were nonwhite.

The investigators calculated that white patients had significantly more bisphosphonate infusions, 21 on average, compared with a mean of 13.5 infusions in nonwhite patients.

The patients were treated with zoledronic acid and/or pamidronate between Jan. 1, 2001, and Oct. 30, 2005. None had prior glucocorticosteroid therapy.

Dr. Aiti of the department of surgical oncology at the University of Illinois at Chicago, called for larger studies to consider not only race, but also confounding variables such as type of bisphosphonate therapy and cumulative dose, as well as other possible risk factors.

ATLANTA — A retrospective analysis of data from nearly 4,000 patients treated with intravenous bisphosphonates suggests that osteonecrosis of the jaw in patients with metastatic cancer is an important but rare event in these patients, Dr. Ana O. Hoff reported in a poster at the annual meeting of the American Society of Clinical Oncology.

Reports of an association between bisphosphonate treatment and osteonecrosis of the jaw (ONJ) in patients with metastatic bone disease prompted this study examining the frequency of and risk factors for ONJ, explained Dr. Hoff of the University of Texas M.D. Anderson Cancer Center, Houston.

The cohort studied included patients treated from September 1996 to February 2004. The most common diagnoses were breast cancer and multiple myeloma, and the indications for intravenous bisphosphonate treatment included metastatic bone disease, hypercalcemia, and osteoporosis.

ONJ, which developed in 29 patients (0.73% overall, including about 1% of breast cancer patients and 2% of multiple myeloma patients), was defined as exposed nonhealing bone of at least 3 months' duration.

Mean cumulative doses of the bisphosphonates used (pamidronate and zoledronate) were significantly higher, and duration of disease and follow-up were significantly longer, in ONJ patients than in those who didn't develop ONJ.

Dental extractions, estrogen-receptor-positive tumors, and treatment with pamidronate and zoledronate were shown to be significant risk factors for ONJ in breast cancer patients. In multiple myeloma patients, significant risk factors were dental extractions, periodontal disease, and osteoporosis.

About 70% of ONJ patients reported no pain with bone exposure, Dr. Hoff noted.

Management of ONJ included aggressive oral hygiene, oral rinses, debridement of necrotic bone, and antibiotic therapy. Of 15 ONJ patients followed longer than 6 months, 1 healed, 1 improved, 1 remained stable, and 9 experienced disease progression.

Race May Be ONJ Risk

White cancer patients on intravenous bisphosphonate therapy for bone metastases may be at higher risk for osteonecrosis of the jaw, Dr. Tamer Aiti reported in a poster at the meeting.

A retrospective study by Dr. Aiti and colleagues at John H. Stroger Jr. Cook County Hospital, Chicago, found that 6 of 161 patients with metastatic breast cancer developed this rare complication in the mandible bone. Five of the six patients were white. Yet whites accounted for less than a third of the population reviewed. All but 29 patients were nonwhite.

The investigators calculated that white patients had significantly more bisphosphonate infusions, 21 on average, compared with a mean of 13.5 infusions in nonwhite patients.

The patients were treated with zoledronic acid and/or pamidronate between Jan. 1, 2001, and Oct. 30, 2005. None had prior glucocorticosteroid therapy.

Dr. Aiti of the department of surgical oncology at the University of Illinois at Chicago, called for larger studies to consider not only race, but also confounding variables such as type of bisphosphonate therapy and cumulative dose, as well as other possible risk factors.

ATLANTA — A retrospective analysis of data from nearly 4,000 patients treated with intravenous bisphosphonates suggests that osteonecrosis of the jaw in patients with metastatic cancer is an important but rare event in these patients, Dr. Ana O. Hoff reported in a poster at the annual meeting of the American Society of Clinical Oncology.

Reports of an association between bisphosphonate treatment and osteonecrosis of the jaw (ONJ) in patients with metastatic bone disease prompted this study examining the frequency of and risk factors for ONJ, explained Dr. Hoff of the University of Texas M.D. Anderson Cancer Center, Houston.

The cohort studied included patients treated from September 1996 to February 2004. The most common diagnoses were breast cancer and multiple myeloma, and the indications for intravenous bisphosphonate treatment included metastatic bone disease, hypercalcemia, and osteoporosis.

ONJ, which developed in 29 patients (0.73% overall, including about 1% of breast cancer patients and 2% of multiple myeloma patients), was defined as exposed nonhealing bone of at least 3 months' duration.

Mean cumulative doses of the bisphosphonates used (pamidronate and zoledronate) were significantly higher, and duration of disease and follow-up were significantly longer, in ONJ patients than in those who didn't develop ONJ.

Dental extractions, estrogen-receptor-positive tumors, and treatment with pamidronate and zoledronate were shown to be significant risk factors for ONJ in breast cancer patients. In multiple myeloma patients, significant risk factors were dental extractions, periodontal disease, and osteoporosis.

About 70% of ONJ patients reported no pain with bone exposure, Dr. Hoff noted.

Management of ONJ included aggressive oral hygiene, oral rinses, debridement of necrotic bone, and antibiotic therapy. Of 15 ONJ patients followed longer than 6 months, 1 healed, 1 improved, 1 remained stable, and 9 experienced disease progression.

Race May Be ONJ Risk

White cancer patients on intravenous bisphosphonate therapy for bone metastases may be at higher risk for osteonecrosis of the jaw, Dr. Tamer Aiti reported in a poster at the meeting.

A retrospective study by Dr. Aiti and colleagues at John H. Stroger Jr. Cook County Hospital, Chicago, found that 6 of 161 patients with metastatic breast cancer developed this rare complication in the mandible bone. Five of the six patients were white. Yet whites accounted for less than a third of the population reviewed. All but 29 patients were nonwhite.

The investigators calculated that white patients had significantly more bisphosphonate infusions, 21 on average, compared with a mean of 13.5 infusions in nonwhite patients.

The patients were treated with zoledronic acid and/or pamidronate between Jan. 1, 2001, and Oct. 30, 2005. None had prior glucocorticosteroid therapy.

Dr. Aiti of the department of surgical oncology at the University of Illinois at Chicago, called for larger studies to consider not only race, but also confounding variables such as type of bisphosphonate therapy and cumulative dose, as well as other possible risk factors.