Osteoarthritis

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study revealed in 2002 that it may increase cardiovascular risk. Experts are exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could help postmenopausal women with very low or even undetectable estradiol levels. This group has a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or placebo for 2 years. Bioavailable estradiol levels were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater drops in osteocalcin and BSAP than women in the highest quintile of bioavailable estradiol in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, versus women in the highest quintile. Spine BMD was unaffected. “Measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover,” wrote the authors

During a press conference, however, Dr. Huang warned it is still not clear whether the women who appear to have the most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also be the most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study revealed in 2002 that it may increase cardiovascular risk. Experts are exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could help postmenopausal women with very low or even undetectable estradiol levels. This group has a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or placebo for 2 years. Bioavailable estradiol levels were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater drops in osteocalcin and BSAP than women in the highest quintile of bioavailable estradiol in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, versus women in the highest quintile. Spine BMD was unaffected. “Measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover,” wrote the authors

During a press conference, however, Dr. Huang warned it is still not clear whether the women who appear to have the most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also be the most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study revealed in 2002 that it may increase cardiovascular risk. Experts are exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could help postmenopausal women with very low or even undetectable estradiol levels. This group has a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or placebo for 2 years. Bioavailable estradiol levels were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater drops in osteocalcin and BSAP than women in the highest quintile of bioavailable estradiol in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, versus women in the highest quintile. Spine BMD was unaffected. “Measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover,” wrote the authors

During a press conference, however, Dr. Huang warned it is still not clear whether the women who appear to have the most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also be the most vulnerable to the effects of hormone therapy on cardiovascular health.

WASHINGTON — Physicians and patients need to work together to decide for or against long-term bisphosphonate treatment for osteoporosis, said Dr. Sundeep Khosla at an international symposium sponsored by the National Osteoporosis Foundation

Alendronate is the longest-available bisphosphonate, with 10 years of follow-up data. In one analysis of 10 years of data for postmenopausal women on varying regimens of alendronate, those on 10 mg daily of alendronate had increased BMD for the spine and hip (N. Engl. J. Med. 2004;350:1189–99). Spine BMD increased by 14% from baseline over that period, and total hip BMD increased by 7%.

Smaller gains in BMD were noted for women on 5 mg daily of alendronate: 9% and 3% for the spine and total hip, respectively.

For women in the discontinuation group, spinal BMD leveled off (an increase of 0.3% from years 6–10) and total hip BMD declined slightly (a decrease of 1% from years 6–10).

This study “told us that alendronate did in fact have sustained effects over 10 years on bone density and bone turnover markers,” said Dr. Khosla, research chair of the division of endocrinology at the Mayo Clinic in Rochester, Minn. However, the fracture data were inconclusive.

In the FLEX (Fracture Intervention Trial [FIT] Long-Term Extension) study, published late last year, researchers assessed the effects of continuing or stopping alendronate after 5 years of treatment (JAMA 2006;296:2927–38).

For women on placebo for years 5–10, total hip BMD returned to baseline levels. Women on 5 mg/day or 10 mg/day of alendronate gained and maintained a 4% increase in hip BMD over baseline during the same period.

Women on placebo during years 5–10 had a slight increase in spine BMD, and women on alendronate had a steeper increase. Women who continued on alendronate for 10 years had an almost 50% reduction in clinical vertebral fractures, compared with those who stopped treatment after 5 years. There was no difference between the groups in terms of nonvertebral or morphometric vertebral fractures.

“Continuation of alendronate for 10 years maintains bone mass and reduces bone remodeling, compared with discontinuation after 5 years,” said Dr. Khosla.

Discontinuation did not increase the risk of nonvertebral fractures or x-ray-detected vertebral fractures, but the risk of clinically detected vertebral fractures was significantly increased in those who discontinued therapy after 5 years.

“For many women, stopping alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of vertebral fractures—such as those who already have a vertebral fracture or those [who might have] very low bone density—may benefit by continuing beyond 5 years.”

WASHINGTON — Physicians and patients need to work together to decide for or against long-term bisphosphonate treatment for osteoporosis, said Dr. Sundeep Khosla at an international symposium sponsored by the National Osteoporosis Foundation

Alendronate is the longest-available bisphosphonate, with 10 years of follow-up data. In one analysis of 10 years of data for postmenopausal women on varying regimens of alendronate, those on 10 mg daily of alendronate had increased BMD for the spine and hip (N. Engl. J. Med. 2004;350:1189–99). Spine BMD increased by 14% from baseline over that period, and total hip BMD increased by 7%.

Smaller gains in BMD were noted for women on 5 mg daily of alendronate: 9% and 3% for the spine and total hip, respectively.

For women in the discontinuation group, spinal BMD leveled off (an increase of 0.3% from years 6–10) and total hip BMD declined slightly (a decrease of 1% from years 6–10).

This study “told us that alendronate did in fact have sustained effects over 10 years on bone density and bone turnover markers,” said Dr. Khosla, research chair of the division of endocrinology at the Mayo Clinic in Rochester, Minn. However, the fracture data were inconclusive.

In the FLEX (Fracture Intervention Trial [FIT] Long-Term Extension) study, published late last year, researchers assessed the effects of continuing or stopping alendronate after 5 years of treatment (JAMA 2006;296:2927–38).

For women on placebo for years 5–10, total hip BMD returned to baseline levels. Women on 5 mg/day or 10 mg/day of alendronate gained and maintained a 4% increase in hip BMD over baseline during the same period.

Women on placebo during years 5–10 had a slight increase in spine BMD, and women on alendronate had a steeper increase. Women who continued on alendronate for 10 years had an almost 50% reduction in clinical vertebral fractures, compared with those who stopped treatment after 5 years. There was no difference between the groups in terms of nonvertebral or morphometric vertebral fractures.

“Continuation of alendronate for 10 years maintains bone mass and reduces bone remodeling, compared with discontinuation after 5 years,” said Dr. Khosla.

Discontinuation did not increase the risk of nonvertebral fractures or x-ray-detected vertebral fractures, but the risk of clinically detected vertebral fractures was significantly increased in those who discontinued therapy after 5 years.

“For many women, stopping alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of vertebral fractures—such as those who already have a vertebral fracture or those [who might have] very low bone density—may benefit by continuing beyond 5 years.”

WASHINGTON — Physicians and patients need to work together to decide for or against long-term bisphosphonate treatment for osteoporosis, said Dr. Sundeep Khosla at an international symposium sponsored by the National Osteoporosis Foundation

Alendronate is the longest-available bisphosphonate, with 10 years of follow-up data. In one analysis of 10 years of data for postmenopausal women on varying regimens of alendronate, those on 10 mg daily of alendronate had increased BMD for the spine and hip (N. Engl. J. Med. 2004;350:1189–99). Spine BMD increased by 14% from baseline over that period, and total hip BMD increased by 7%.

Smaller gains in BMD were noted for women on 5 mg daily of alendronate: 9% and 3% for the spine and total hip, respectively.

For women in the discontinuation group, spinal BMD leveled off (an increase of 0.3% from years 6–10) and total hip BMD declined slightly (a decrease of 1% from years 6–10).

This study “told us that alendronate did in fact have sustained effects over 10 years on bone density and bone turnover markers,” said Dr. Khosla, research chair of the division of endocrinology at the Mayo Clinic in Rochester, Minn. However, the fracture data were inconclusive.

In the FLEX (Fracture Intervention Trial [FIT] Long-Term Extension) study, published late last year, researchers assessed the effects of continuing or stopping alendronate after 5 years of treatment (JAMA 2006;296:2927–38).

For women on placebo for years 5–10, total hip BMD returned to baseline levels. Women on 5 mg/day or 10 mg/day of alendronate gained and maintained a 4% increase in hip BMD over baseline during the same period.

Women on placebo during years 5–10 had a slight increase in spine BMD, and women on alendronate had a steeper increase. Women who continued on alendronate for 10 years had an almost 50% reduction in clinical vertebral fractures, compared with those who stopped treatment after 5 years. There was no difference between the groups in terms of nonvertebral or morphometric vertebral fractures.

“Continuation of alendronate for 10 years maintains bone mass and reduces bone remodeling, compared with discontinuation after 5 years,” said Dr. Khosla.

Discontinuation did not increase the risk of nonvertebral fractures or x-ray-detected vertebral fractures, but the risk of clinically detected vertebral fractures was significantly increased in those who discontinued therapy after 5 years.

“For many women, stopping alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of vertebral fractures—such as those who already have a vertebral fracture or those [who might have] very low bone density—may benefit by continuing beyond 5 years.”

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

CHICAGO — The risk of jaw osteonecrosis increases with the number of bisphosphonate infusions, according to studies presented at the annual meeting of the American Society of Clinical Oncology.

Osteonecrosis of the jaw (ONJ) is a rare but serious side effect of bisphosphonates that has popped up in a number of case reports in the literature. Three groups of researchers conducted retrospective analyses to understand the natural history, incidence, and risk factors of this side effect.

In one study, Dr. Tracey L. O'Connor of Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues identified 354 patients with metastatic cancer involving bones on intravenous bisphosphonates between 2002 and 2006 at the Institute. Using dental records, they identified 25 patients (7%) with ONJ. Most (80%) had breast cancer, and 27% had a medical comorbidity such as diabetes mellitus, hypertension, or chronic anticoagulation therapy for deep vein thrombosis or pulmonary embolism. In general, patients who developed ONJ had more bisphosphonate infusions—an average of 11—versus patients without ONJ (an average of 7 infusions). Most ONJ patients (52%) had stage 1 disease (exposed necrotic cortical bone); 36% had stage 2 (localized involvement of the mandible); and 12% had stage 3 (diffuse involvement of the mandible). Most (84%) were managed with antibiotics; 16% had debridement and alveoplasty. “If detected early, ONJ can be conservatively managed,” the authors wrote.

To see if scintigraphy could predict ONJ, planar whole body scans were performed 3 hours after injection of Tc-99m methylene diphosphonate using anterior and posterior perspectives. Jaw uptake was graded relative to normal posterior uptake within the ileum (grade 1), sacrum (grade 2), and sacroiliac joints (grade 3). In ONJ patients, 14 had bone scans, and 13 showed grade 3 uptake. In comparison, 183 controls had bone scans; of these, 128 (70%) had grade 3 uptake. “Uptake on bone scans is not a reliable predictor of ONJ,” the authors wrote.

In another study, Dr. Matthew R. Stumpe, an otolaryngology resident at the University of Tennessee, Memphis, and colleagues performed a retrospective review of 638 patients treated with intravenous bisphosphonate therapy for cancer. The most common malignancies were prostate, lung, breast, and multiple myeloma. Most patients were treated with pamidronate (53%), followed by zoledronic acid (26%). The rest were treated with both drugs.

“Patients who developed osteonecrosis underwent a greater number of bisphosphonate infusions and greater total infusion hours, suggesting a positive correlation between osteonecrosis and drug dose,” the authors wrote. In all, six patients had ONJ, or 0.94%. Patients with ONJ had a significantly greater number of infusions (21), versus controls (11) and a significantly greater mean number of hours of infusion time (43 vs. 18). All ONJ patients presented with exposed bone. In four, ONJ occurred after dental treatment. The mandible was affected in five patients; the maxilla in one. Bisphosphonates were discontinued in five patients after ONJ diagnosis. The patient who did not stop had a small area of exposed bone covered surgically using viable mucosa. Another patient recovered from ONJ and resumed bisphosphonates.

Dr. Mimi I. Hu of the department of endocrine neoplasia and hormonal disorders at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues performed a retrospective analysis of patients treated with intravenous bisphosphonates between 1996 and 2004. They identified 4,025 patients; 35 had ONJ. Fourteen were followed for over 6 months at a dental clinic. Patients were evenly split between having breast cancer or multiple myeloma. The average length of exposed bone at the initial evaluation was 11 mm. Most (10) were treated with pamidronate followed by zoledronic acid. Four were treated with zoledronic acid alone. The median cumulative dose was 1,710 mg for pamidronate and 72 mg for zoledronic acid. The median duration of follow-up from initial diagnosis was 17 months.

The researchers focused on the natural course of ONJ. ONJ resolved in 21% of long-term follow-up patients. On the basis of the change in the lesion from baseline to last noted size, seven patients had progression. Two were stable, one regressed, one had recurrences at different sites over 67 months, and three had resolution for over a year. Modification of therapy doesn't appear linked to resolution, the researchers noted. In some patients, persistent ONJ was seen whether therapy was discontinued, decreased in frequency, or continued at the same dose and frequency. In others, resolution occurred if intravenous bisphosphonate therapy was discontinued, decreased in frequency, and replaced by weekly oral alendronate.

DALLAS — Surgical repair of hip fracture in the elderly is linked to a high risk of postoperative MI or death—a reality not reflected in current American College of Cardiology/American Heart Association preoperative cardiovascular evaluation guidelines, Dr. Jeanne Huddleston said at the annual meeting of the Society of Hospital Medicine.

The guidelines lump all orthopedic surgical procedures in an intermediate-risk category, meaning their combined risk of postoperative MI or death is expected to be less than 5%. That's true of elective total hip arthroplasty, but hip fracture repair is different, said Dr. Huddleston, a hospitalist at the Mayo Clinic, Rochester, Minn., and former society president.

She presented a population-based retrospective study of 1,197 patients who underwent repair of a fractured hip and 693 who had hip replacement. During a mean hospital stay of 8.9 days, the incidence rates of postoperative MI, heart failure, and mortality were markedly lower in the elective hip arthroplasty group (see chart). Moreover, the combined 1-year rate of MI and all-cause mortality was 34.2% in patients undergoing fracture repair, versus 7.5% in the arthroplasty group. Adjusting for age, gender, and American Society of Anesthesiologists physical status classification, racture repair patients were 3.6-fold more likely to have an MI or die within a year postsurgery.

Hip fracture repair is typically done on an urgent basis, but doesn't fall within the definition of “emergency” surgery in guidelines. Since it's considered nonemergent, physicians can take up to 48 hours postfracture to optimize cardiac status—a sound strategy given the high CV risk, according to Dr. Huddleston.

ELSEVIER GLOBAL MEDICAL NEWS

DALLAS — Surgical repair of hip fracture in the elderly is linked to a high risk of postoperative MI or death—a reality not reflected in current American College of Cardiology/American Heart Association preoperative cardiovascular evaluation guidelines, Dr. Jeanne Huddleston said at the annual meeting of the Society of Hospital Medicine.

The guidelines lump all orthopedic surgical procedures in an intermediate-risk category, meaning their combined risk of postoperative MI or death is expected to be less than 5%. That's true of elective total hip arthroplasty, but hip fracture repair is different, said Dr. Huddleston, a hospitalist at the Mayo Clinic, Rochester, Minn., and former society president.

She presented a population-based retrospective study of 1,197 patients who underwent repair of a fractured hip and 693 who had hip replacement. During a mean hospital stay of 8.9 days, the incidence rates of postoperative MI, heart failure, and mortality were markedly lower in the elective hip arthroplasty group (see chart). Moreover, the combined 1-year rate of MI and all-cause mortality was 34.2% in patients undergoing fracture repair, versus 7.5% in the arthroplasty group. Adjusting for age, gender, and American Society of Anesthesiologists physical status classification, racture repair patients were 3.6-fold more likely to have an MI or die within a year postsurgery.

Hip fracture repair is typically done on an urgent basis, but doesn't fall within the definition of “emergency” surgery in guidelines. Since it's considered nonemergent, physicians can take up to 48 hours postfracture to optimize cardiac status—a sound strategy given the high CV risk, according to Dr. Huddleston.

ELSEVIER GLOBAL MEDICAL NEWS

DALLAS — Surgical repair of hip fracture in the elderly is linked to a high risk of postoperative MI or death—a reality not reflected in current American College of Cardiology/American Heart Association preoperative cardiovascular evaluation guidelines, Dr. Jeanne Huddleston said at the annual meeting of the Society of Hospital Medicine.

The guidelines lump all orthopedic surgical procedures in an intermediate-risk category, meaning their combined risk of postoperative MI or death is expected to be less than 5%. That's true of elective total hip arthroplasty, but hip fracture repair is different, said Dr. Huddleston, a hospitalist at the Mayo Clinic, Rochester, Minn., and former society president.

She presented a population-based retrospective study of 1,197 patients who underwent repair of a fractured hip and 693 who had hip replacement. During a mean hospital stay of 8.9 days, the incidence rates of postoperative MI, heart failure, and mortality were markedly lower in the elective hip arthroplasty group (see chart). Moreover, the combined 1-year rate of MI and all-cause mortality was 34.2% in patients undergoing fracture repair, versus 7.5% in the arthroplasty group. Adjusting for age, gender, and American Society of Anesthesiologists physical status classification, racture repair patients were 3.6-fold more likely to have an MI or die within a year postsurgery.

Hip fracture repair is typically done on an urgent basis, but doesn't fall within the definition of “emergency” surgery in guidelines. Since it's considered nonemergent, physicians can take up to 48 hours postfracture to optimize cardiac status—a sound strategy given the high CV risk, according to Dr. Huddleston.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A careful evaluation and thorough history can identify a large portion of secondary osteoporosis patients, Dr. Meryl LeBoff, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women's Hospital in Boston, said at an international symposium sponsored by the National Osteoporosis Foundation.

The true prevalence of secondary osteoporosis is not known. However, about 50% of patients can be detected with a good medical history, said Dr. LeBoff. While laboratory evaluations vary, such tests can be used to identify 25%–65% of patients with secondary osteoporosis.

Identifying secondary osteoporosis is crucial because skeletal changes may be reversible and decreased acquisition of peak bone mass is a determinant of osteoporosis later in life.

In a 2004 report on bone health and osteoporosis, the surgeon general recommended that all patients diagnosed with osteoporosis get at least a limited evaluation for secondary causes of bone loss.

In particular, premenopausal women or men with unexplained fractures and those who are adherent but have a poor response to therapy should be evaluated for secondary osteoporosis.

A low z score—which compares a patient's bone mineral density (BMD) to the mean for a healthy age- and gender-matched population—may suggest an increased likelihood of secondary osteoporosis. A z score of −1.0 is tied to a twofold greater lifetime risk of fracture and a z score of −2.0 is associated with a fourfold greater lifetime risk of fracture. Patients with a low z score are most in need of in-depth evaluation for secondary osteoporosis.

“However, z scores do not consistently predict which patient has an underlying disorder, so it's important to use clinical judgement in the evaluation of a particular patient,” said Dr. LeBoff.

There are no evidence-based guides for evaluating a patient for secondary osteoporosis. Dr. LeBoff recommends a detailed personal and family history. Be sure to ask about calcium intake. In addition to a thorough physical exam, do bone density testing and laboratory tests.

Laboratory tests for serum calcium, 25-hydroxy vitamin D, 24-hour urinary calcium, and parathyroid hormone—plus serum thyroid-stimulating hormone among women on thyroid replacement—can identify an estimated 98% of patients with secondary osteoporosis (J. Clin. Endocrinol. Metab. 2002;87:4431–7).

At the Brigham and Women's osteoporosis center, evaluation guidelines for secondary osteoporosis include a z score less than −1.5. Laboratory tests include serum calcium and phosphorus, renal function, 25-hydroxy vitamin D levels, thyroid-stimulating hormone, parathyroid hormone, and urinary calcium. In select patients, bone turnover markers are tested.

Dr. LeBoff also discussed some common causes of secondary osteoporosis:

▸ Glucocorticoids. “Use of glucocorticoids is the most common cause of secondary osteoporosis,” said Dr. LeBoff. A number of other endocrine abnormalities—thyroid hormone excess, hypogonadism, anorexia, hyperparathyroidism, hypercalciuria, vitamin D deficiency, and androgen insensitivity—can also cause secondary osteoporosis.

Glucocorticoids increase fracture risk progressively. “Even extremely low doses of inhaled glucocorticoids can lead to bone loss,” said Dr. LeBoff.

The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, involving decreased osteoblast function, increased osteoblast apoptosis, increased gastrointestinal absorption of calcium, increased urinary calcium excretion, and an increase in osteoclast bone resorption.

▸ Anorexia. This disorder affects an estimated 4% of U.S. college students and leads to a 25% lower spine BMD and a sevenfold increased fracture risk. Peak bone mass is decreased and there may be a permanent deficit of bone mass. Anorexic women have subnormal levels of dehydroepiandrosterone, testosterone, estrogen, and cortisol. “Estrogen does not correct the low bone mass [in these women],” said Dr. LeBoff. A number of trials attempting to reverse lost bone mass in anorexic women are underway.

▸ Vitamin D deficiency. Vitamin D deficiency is common and has been implicated in impaired muscle function, increased falls, increased muscle pain, multiple sclerosis, and some malignancies. There is seasonal variation in vitamin D levels. Notably, vitamin D activation decreases with age, darker skin pigment, and increased sunblock use. Gastrointestinal disorders can lead to vitamin D deficiency, as it is absorbed in the small intestine.

“Vitamin D deficiency is currently defined as 25-hydroxy vitamin D level of less than 20 ng/mL … sufficiency for bone is [25-hydroxy vitamin D level] greater than 30–32 ng/mL,” said Dr. LeBoff.

Inadequate levels of vitamin D have been documented in 52% of women who participated in osteoporosis trials. Women in these studies had an average T score of −1.8.

In a study at Brigham and Women's, 90% of women admitted with hip fractures had vitamin D insufficiency and 57% had vitamin D deficiency. Because of this, when women are admitted now with hip fragility fracture they are given 50,000 units of vitamin D. They are also evaluated for secondary osteoporosis.

▸ Aromatase inhibitors. “Bone loss is clearly associated with breast cancer therapies,” said Dr. LeBoff. Aromatase inhibitors can lead to bone loss of about 2.6% per year, though long-term data are not yet available. Gonadotropin-releasing hormones can lead to bone loss of 4%–6% per year. Ovarian failure can lead to bone loss of about 8% per year. Oophorectomy is associated with bone loss of 11% per year.

WASHINGTON — A careful evaluation and thorough history can identify a large portion of secondary osteoporosis patients, Dr. Meryl LeBoff, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women's Hospital in Boston, said at an international symposium sponsored by the National Osteoporosis Foundation.

The true prevalence of secondary osteoporosis is not known. However, about 50% of patients can be detected with a good medical history, said Dr. LeBoff. While laboratory evaluations vary, such tests can be used to identify 25%–65% of patients with secondary osteoporosis.

Identifying secondary osteoporosis is crucial because skeletal changes may be reversible and decreased acquisition of peak bone mass is a determinant of osteoporosis later in life.

In a 2004 report on bone health and osteoporosis, the surgeon general recommended that all patients diagnosed with osteoporosis get at least a limited evaluation for secondary causes of bone loss.

In particular, premenopausal women or men with unexplained fractures and those who are adherent but have a poor response to therapy should be evaluated for secondary osteoporosis.

A low z score—which compares a patient's bone mineral density (BMD) to the mean for a healthy age- and gender-matched population—may suggest an increased likelihood of secondary osteoporosis. A z score of −1.0 is tied to a twofold greater lifetime risk of fracture and a z score of −2.0 is associated with a fourfold greater lifetime risk of fracture. Patients with a low z score are most in need of in-depth evaluation for secondary osteoporosis.

“However, z scores do not consistently predict which patient has an underlying disorder, so it's important to use clinical judgement in the evaluation of a particular patient,” said Dr. LeBoff.

There are no evidence-based guides for evaluating a patient for secondary osteoporosis. Dr. LeBoff recommends a detailed personal and family history. Be sure to ask about calcium intake. In addition to a thorough physical exam, do bone density testing and laboratory tests.

Laboratory tests for serum calcium, 25-hydroxy vitamin D, 24-hour urinary calcium, and parathyroid hormone—plus serum thyroid-stimulating hormone among women on thyroid replacement—can identify an estimated 98% of patients with secondary osteoporosis (J. Clin. Endocrinol. Metab. 2002;87:4431–7).

At the Brigham and Women's osteoporosis center, evaluation guidelines for secondary osteoporosis include a z score less than −1.5. Laboratory tests include serum calcium and phosphorus, renal function, 25-hydroxy vitamin D levels, thyroid-stimulating hormone, parathyroid hormone, and urinary calcium. In select patients, bone turnover markers are tested.

Dr. LeBoff also discussed some common causes of secondary osteoporosis:

▸ Glucocorticoids. “Use of glucocorticoids is the most common cause of secondary osteoporosis,” said Dr. LeBoff. A number of other endocrine abnormalities—thyroid hormone excess, hypogonadism, anorexia, hyperparathyroidism, hypercalciuria, vitamin D deficiency, and androgen insensitivity—can also cause secondary osteoporosis.

Glucocorticoids increase fracture risk progressively. “Even extremely low doses of inhaled glucocorticoids can lead to bone loss,” said Dr. LeBoff.

The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, involving decreased osteoblast function, increased osteoblast apoptosis, increased gastrointestinal absorption of calcium, increased urinary calcium excretion, and an increase in osteoclast bone resorption.

▸ Anorexia. This disorder affects an estimated 4% of U.S. college students and leads to a 25% lower spine BMD and a sevenfold increased fracture risk. Peak bone mass is decreased and there may be a permanent deficit of bone mass. Anorexic women have subnormal levels of dehydroepiandrosterone, testosterone, estrogen, and cortisol. “Estrogen does not correct the low bone mass [in these women],” said Dr. LeBoff. A number of trials attempting to reverse lost bone mass in anorexic women are underway.

▸ Vitamin D deficiency. Vitamin D deficiency is common and has been implicated in impaired muscle function, increased falls, increased muscle pain, multiple sclerosis, and some malignancies. There is seasonal variation in vitamin D levels. Notably, vitamin D activation decreases with age, darker skin pigment, and increased sunblock use. Gastrointestinal disorders can lead to vitamin D deficiency, as it is absorbed in the small intestine.

“Vitamin D deficiency is currently defined as 25-hydroxy vitamin D level of less than 20 ng/mL … sufficiency for bone is [25-hydroxy vitamin D level] greater than 30–32 ng/mL,” said Dr. LeBoff.

Inadequate levels of vitamin D have been documented in 52% of women who participated in osteoporosis trials. Women in these studies had an average T score of −1.8.

In a study at Brigham and Women's, 90% of women admitted with hip fractures had vitamin D insufficiency and 57% had vitamin D deficiency. Because of this, when women are admitted now with hip fragility fracture they are given 50,000 units of vitamin D. They are also evaluated for secondary osteoporosis.

▸ Aromatase inhibitors. “Bone loss is clearly associated with breast cancer therapies,” said Dr. LeBoff. Aromatase inhibitors can lead to bone loss of about 2.6% per year, though long-term data are not yet available. Gonadotropin-releasing hormones can lead to bone loss of 4%–6% per year. Ovarian failure can lead to bone loss of about 8% per year. Oophorectomy is associated with bone loss of 11% per year.

WASHINGTON — A careful evaluation and thorough history can identify a large portion of secondary osteoporosis patients, Dr. Meryl LeBoff, director of the skeletal health and osteoporosis center and bone density unit at Brigham and Women's Hospital in Boston, said at an international symposium sponsored by the National Osteoporosis Foundation.

The true prevalence of secondary osteoporosis is not known. However, about 50% of patients can be detected with a good medical history, said Dr. LeBoff. While laboratory evaluations vary, such tests can be used to identify 25%–65% of patients with secondary osteoporosis.

Identifying secondary osteoporosis is crucial because skeletal changes may be reversible and decreased acquisition of peak bone mass is a determinant of osteoporosis later in life.

In a 2004 report on bone health and osteoporosis, the surgeon general recommended that all patients diagnosed with osteoporosis get at least a limited evaluation for secondary causes of bone loss.

In particular, premenopausal women or men with unexplained fractures and those who are adherent but have a poor response to therapy should be evaluated for secondary osteoporosis.

A low z score—which compares a patient's bone mineral density (BMD) to the mean for a healthy age- and gender-matched population—may suggest an increased likelihood of secondary osteoporosis. A z score of −1.0 is tied to a twofold greater lifetime risk of fracture and a z score of −2.0 is associated with a fourfold greater lifetime risk of fracture. Patients with a low z score are most in need of in-depth evaluation for secondary osteoporosis.

“However, z scores do not consistently predict which patient has an underlying disorder, so it's important to use clinical judgement in the evaluation of a particular patient,” said Dr. LeBoff.

There are no evidence-based guides for evaluating a patient for secondary osteoporosis. Dr. LeBoff recommends a detailed personal and family history. Be sure to ask about calcium intake. In addition to a thorough physical exam, do bone density testing and laboratory tests.

Laboratory tests for serum calcium, 25-hydroxy vitamin D, 24-hour urinary calcium, and parathyroid hormone—plus serum thyroid-stimulating hormone among women on thyroid replacement—can identify an estimated 98% of patients with secondary osteoporosis (J. Clin. Endocrinol. Metab. 2002;87:4431–7).

At the Brigham and Women's osteoporosis center, evaluation guidelines for secondary osteoporosis include a z score less than −1.5. Laboratory tests include serum calcium and phosphorus, renal function, 25-hydroxy vitamin D levels, thyroid-stimulating hormone, parathyroid hormone, and urinary calcium. In select patients, bone turnover markers are tested.

Dr. LeBoff also discussed some common causes of secondary osteoporosis:

▸ Glucocorticoids. “Use of glucocorticoids is the most common cause of secondary osteoporosis,” said Dr. LeBoff. A number of other endocrine abnormalities—thyroid hormone excess, hypogonadism, anorexia, hyperparathyroidism, hypercalciuria, vitamin D deficiency, and androgen insensitivity—can also cause secondary osteoporosis.

Glucocorticoids increase fracture risk progressively. “Even extremely low doses of inhaled glucocorticoids can lead to bone loss,” said Dr. LeBoff.

The pathophysiology of glucocorticoid-induced osteoporosis is multifactorial, involving decreased osteoblast function, increased osteoblast apoptosis, increased gastrointestinal absorption of calcium, increased urinary calcium excretion, and an increase in osteoclast bone resorption.

▸ Anorexia. This disorder affects an estimated 4% of U.S. college students and leads to a 25% lower spine BMD and a sevenfold increased fracture risk. Peak bone mass is decreased and there may be a permanent deficit of bone mass. Anorexic women have subnormal levels of dehydroepiandrosterone, testosterone, estrogen, and cortisol. “Estrogen does not correct the low bone mass [in these women],” said Dr. LeBoff. A number of trials attempting to reverse lost bone mass in anorexic women are underway.

▸ Vitamin D deficiency. Vitamin D deficiency is common and has been implicated in impaired muscle function, increased falls, increased muscle pain, multiple sclerosis, and some malignancies. There is seasonal variation in vitamin D levels. Notably, vitamin D activation decreases with age, darker skin pigment, and increased sunblock use. Gastrointestinal disorders can lead to vitamin D deficiency, as it is absorbed in the small intestine.

“Vitamin D deficiency is currently defined as 25-hydroxy vitamin D level of less than 20 ng/mL … sufficiency for bone is [25-hydroxy vitamin D level] greater than 30–32 ng/mL,” said Dr. LeBoff.

Inadequate levels of vitamin D have been documented in 52% of women who participated in osteoporosis trials. Women in these studies had an average T score of −1.8.

In a study at Brigham and Women's, 90% of women admitted with hip fractures had vitamin D insufficiency and 57% had vitamin D deficiency. Because of this, when women are admitted now with hip fragility fracture they are given 50,000 units of vitamin D. They are also evaluated for secondary osteoporosis.

▸ Aromatase inhibitors. “Bone loss is clearly associated with breast cancer therapies,” said Dr. LeBoff. Aromatase inhibitors can lead to bone loss of about 2.6% per year, though long-term data are not yet available. Gonadotropin-releasing hormones can lead to bone loss of 4%–6% per year. Ovarian failure can lead to bone loss of about 8% per year. Oophorectomy is associated with bone loss of 11% per year.

SAN FRANCISCO — When you're seeing patients who are taking bisphosphonate drugs for osteoporosis, don't forget to look in their mouths, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Osteonecrosis of the jaw recently was added to the precautions section of the prescribing information for all intravenous and oral bisphosphonates, so it is incumbent upon clinicians to look for this very rare complication.

“One of the things I've changed in my clinical practice in the past couple of years is that I laid in a supply of tongue depressors and I've started to look in people's mouths, which I was not routinely doing before,” said Dr. Harris of the university.

Media reports about this side effect of bisphosphonates have caught the attention of patients, some of whom raise concerns about it during visits, he added.

Though no universally accepted definition exists for osteonecrosis of the jaw, a growing consensus characterizes it as an oral cavity lesion with one or more bare bone spots, in the absence of local malignancy or radiation therapy to the head and neck. This is not the same as a patient on bisphosphonate therapy complaining of tooth pain.

“This is a look in the mouth, and there is bone where there should be normal pink mucosa,” Dr. Harris said.

Osteonecrosis of the jaw primarily has been seen in cancer patients receiving high-dose intravenous bisphosphonates therapy, usually monthly. In that population, approximately 0.5%–10% of patients may develop osteonecrosis of the jaw, a range affected by the underlying malignancy.

In patients on oral bisphosphonates, however, rough estimates suggest perhaps 1 patient per 100,000 may develop osteonecrosis of the jaw per year, he said.

The pathophysiology of this disorder is not understood.

Known risk factors for osteonecrosis of the jaw include cancer; concomitant therapies like chemotherapy, radiation, or corticosteroids; poor oral hygiene; and comorbid disorders such as preexisting dental disease, anemia, coagulopathy, or infection.

Be vigilant in patients with poor dental hygiene or procedures such as tooth pulling or teeth implants, Dr. Harris said.

SAN FRANCISCO — When you're seeing patients who are taking bisphosphonate drugs for osteoporosis, don't forget to look in their mouths, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Osteonecrosis of the jaw recently was added to the precautions section of the prescribing information for all intravenous and oral bisphosphonates, so it is incumbent upon clinicians to look for this very rare complication.

“One of the things I've changed in my clinical practice in the past couple of years is that I laid in a supply of tongue depressors and I've started to look in people's mouths, which I was not routinely doing before,” said Dr. Harris of the university.

Media reports about this side effect of bisphosphonates have caught the attention of patients, some of whom raise concerns about it during visits, he added.

Though no universally accepted definition exists for osteonecrosis of the jaw, a growing consensus characterizes it as an oral cavity lesion with one or more bare bone spots, in the absence of local malignancy or radiation therapy to the head and neck. This is not the same as a patient on bisphosphonate therapy complaining of tooth pain.

“This is a look in the mouth, and there is bone where there should be normal pink mucosa,” Dr. Harris said.

Osteonecrosis of the jaw primarily has been seen in cancer patients receiving high-dose intravenous bisphosphonates therapy, usually monthly. In that population, approximately 0.5%–10% of patients may develop osteonecrosis of the jaw, a range affected by the underlying malignancy.

In patients on oral bisphosphonates, however, rough estimates suggest perhaps 1 patient per 100,000 may develop osteonecrosis of the jaw per year, he said.

The pathophysiology of this disorder is not understood.

Known risk factors for osteonecrosis of the jaw include cancer; concomitant therapies like chemotherapy, radiation, or corticosteroids; poor oral hygiene; and comorbid disorders such as preexisting dental disease, anemia, coagulopathy, or infection.

Be vigilant in patients with poor dental hygiene or procedures such as tooth pulling or teeth implants, Dr. Harris said.

SAN FRANCISCO — When you're seeing patients who are taking bisphosphonate drugs for osteoporosis, don't forget to look in their mouths, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Osteonecrosis of the jaw recently was added to the precautions section of the prescribing information for all intravenous and oral bisphosphonates, so it is incumbent upon clinicians to look for this very rare complication.

“One of the things I've changed in my clinical practice in the past couple of years is that I laid in a supply of tongue depressors and I've started to look in people's mouths, which I was not routinely doing before,” said Dr. Harris of the university.

Media reports about this side effect of bisphosphonates have caught the attention of patients, some of whom raise concerns about it during visits, he added.

Though no universally accepted definition exists for osteonecrosis of the jaw, a growing consensus characterizes it as an oral cavity lesion with one or more bare bone spots, in the absence of local malignancy or radiation therapy to the head and neck. This is not the same as a patient on bisphosphonate therapy complaining of tooth pain.

“This is a look in the mouth, and there is bone where there should be normal pink mucosa,” Dr. Harris said.

Osteonecrosis of the jaw primarily has been seen in cancer patients receiving high-dose intravenous bisphosphonates therapy, usually monthly. In that population, approximately 0.5%–10% of patients may develop osteonecrosis of the jaw, a range affected by the underlying malignancy.

In patients on oral bisphosphonates, however, rough estimates suggest perhaps 1 patient per 100,000 may develop osteonecrosis of the jaw per year, he said.

The pathophysiology of this disorder is not understood.

Known risk factors for osteonecrosis of the jaw include cancer; concomitant therapies like chemotherapy, radiation, or corticosteroids; poor oral hygiene; and comorbid disorders such as preexisting dental disease, anemia, coagulopathy, or infection.

Be vigilant in patients with poor dental hygiene or procedures such as tooth pulling or teeth implants, Dr. Harris said.

WASHINGTON — With the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are popping up all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). The answer depends on whom you ask, judging from four poster presentations.

Two studies with researchers from Roche Laboratories Inc. (codeveloper of Boniva, with GlaxoSmithKline) suggested women prefer once-monthly ibandronate and are more likely to persist with it.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate. Persistence was assessed for a 9-month follow-up period.

The unadjusted 9-month persistence rates were 41% for patients on monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy. Monthly ibandronate users were 31% more likely to be persistent versus those on weekly drugs after controlling for age, copay, comorbidities, and prescriptions for more than a 30-day supply.

In a second study, postmenopausal women were enrolled in a prospective, open-label study if they'd been receiving alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for at least 3 months. The women were given once-monthly ibandronate (150 mg) for 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. The survey covered domains of convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of women preferred once-monthly ibandronate, while 8% preferred once-weekly therapy and 5% did not cite a preference. Overall, 70% in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, versus previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly doses. Stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy were associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies with researchers from Merck & Co. (maker of Fosamax), ibandronate offered no advantage in persistence over alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research for Merck and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription information for over 150 million patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. Women were excluded if they had a prescription for any bisphosphonate during the 12 months prior to the index date. All were followed for 1 year. They were considered persistent users if they did not have a therapy break of over 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate respectively had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, versus those on alendronate.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonates. The data came from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. In this study, the researchers worked with a large pharmacy (over 3,000 stores in 28 states).

Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.

WASHINGTON — With the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are popping up all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). The answer depends on whom you ask, judging from four poster presentations.

Two studies with researchers from Roche Laboratories Inc. (codeveloper of Boniva, with GlaxoSmithKline) suggested women prefer once-monthly ibandronate and are more likely to persist with it.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate. Persistence was assessed for a 9-month follow-up period.

The unadjusted 9-month persistence rates were 41% for patients on monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy. Monthly ibandronate users were 31% more likely to be persistent versus those on weekly drugs after controlling for age, copay, comorbidities, and prescriptions for more than a 30-day supply.

In a second study, postmenopausal women were enrolled in a prospective, open-label study if they'd been receiving alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for at least 3 months. The women were given once-monthly ibandronate (150 mg) for 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. The survey covered domains of convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of women preferred once-monthly ibandronate, while 8% preferred once-weekly therapy and 5% did not cite a preference. Overall, 70% in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, versus previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly doses. Stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy were associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies with researchers from Merck & Co. (maker of Fosamax), ibandronate offered no advantage in persistence over alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research for Merck and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription information for over 150 million patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. Women were excluded if they had a prescription for any bisphosphonate during the 12 months prior to the index date. All were followed for 1 year. They were considered persistent users if they did not have a therapy break of over 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate respectively had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, versus those on alendronate.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonates. The data came from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. In this study, the researchers worked with a large pharmacy (over 3,000 stores in 28 states).

Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.

WASHINGTON — With the number of osteoporosis patients expected to grow, the battle for market share among osteoporosis drugs is heated. New data are popping up all the time, including results from several studies presented at an international symposium sponsored by the National Osteoporosis Foundation.

For oral bisphosphonates, the question is whether women are more likely to stick with weekly formulations, like alendronate (Fosamax) and risedronate (Actonel), or monthly formulations, like ibandronate (Boniva). The answer depends on whom you ask, judging from four poster presentations.

Two studies with researchers from Roche Laboratories Inc. (codeveloper of Boniva, with GlaxoSmithKline) suggested women prefer once-monthly ibandronate and are more likely to persist with it.

In the first study, Dr. John A. Sunyecz of Laurel Highlands Ob.Gyn. in Hopwood, Pa., and colleagues assessed data from the HealthCare Integrated Research database, which contains claims data for roughly 17.5 million patients. Persistence was estimated as the proportion of patients who remained on therapy with no refill gaps based on a grace period, determined by the dosing window for weekly bisphosphonates (30-day gap) and monthly ibandronate (45-day gap).

Data collection began in April 2005 and is ongoing. Researchers identified women at least 45 years old with at least one claim for a monthly (ibandronate) or weekly (alendronate or risedronate) bisphosphonate. A total of 4,335 women were identified on alendronate or risedronate and 213 on ibandronate. Persistence was assessed for a 9-month follow-up period.

The unadjusted 9-month persistence rates were 41% for patients on monthly ibandronate and 33% for those on weekly bisphosphonates. The median time to discontinuation was 145 days for those on ibandronate and 115 days for those on weekly therapy. Monthly ibandronate users were 31% more likely to be persistent versus those on weekly drugs after controlling for age, copay, comorbidities, and prescriptions for more than a 30-day supply.

In a second study, postmenopausal women were enrolled in a prospective, open-label study if they'd been receiving alendronate or risedronate for the prevention or treatment of osteoporosis or osteopenia for at least 3 months. The women were given once-monthly ibandronate (150 mg) for 6 months, wrote Dr. Neil C. Binkley, associate director of the University of Wisconsin, Madison, Institute on Aging.

A total of 1,678 women completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) at baseline and at the end of the study or upon withdrawal. The survey covered domains of convenience, quality of life, overall satisfaction, and side effects. Greater scores represented greater satisfaction. The summary score was the average of the four domain scores converted to a 100-point scale. Patients also completed a four-item preference questionnaire after the OPSAT-Q at 6 months.

After 6 months, 74% of women preferred once-monthly ibandronate, while 8% preferred once-weekly therapy and 5% did not cite a preference. Overall, 70% in the intention-to-treat population showed improvement in satisfaction with monthly ibandronate, versus previous weekly therapy, after 6 months. The summary score and convenience, quality-of-life, and overall satisfaction domain scores improved.

Compliance with ibandronate was 96%, with 94% taking at least 80% of their monthly doses. Stomach upset within 48 hours of dosing or missing three doses over 3 months with previous weekly therapy were associated with improved treatment satisfaction after 6 months of monthly ibandronate therapy.

However, in two studies with researchers from Merck & Co. (maker of Fosamax), ibandronate offered no advantage in persistence over alendronate.

In the first study, Thomas W. Weiss, Dr.P.H., of U.S. Outcomes Research for Merck and his colleagues assessed data from the Longitudinal Prescription database, which contains prescription information for over 150 million patients. Data were collected for the period of September 2004 to November 2006.

Women at least 50 years old were included if they filled a new prescription for weekly alendronate, weekly risedronate, or monthly ibandronate. Women were excluded if they had a prescription for any bisphosphonate during the 12 months prior to the index date. All were followed for 1 year. They were considered persistent users if they did not have a therapy break of over 30 days between the end of one prescription's supply and the beginning of the next.

The results included 84,399 women on alendronate, 51,588 on risedronate, and 29,998 on ibandronate. In all, 46%, 48%, and 54% of the women on alendronate, risedronate, and ibandronate respectively had no refills after the initial prescription. Patients with an index prescription for once-monthly ibandronate were 39% more likely to discontinue after filling their first prescription, versus those on alendronate.

In a second study, Dr. Weiss and colleagues assessed the differences in women who persisted on weekly vs. monthly bisphosphonates. The data came from the Drivers of Adherence to Bisphosphonate Therapy (DASH) study. In this study, the researchers worked with a large pharmacy (over 3,000 stores in 28 states).

Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.

Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.

However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.

Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.

But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.

However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.

For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.

BMD 'is lower when anorexia nervosa begins in adolescence than when it occurs in adult life.' DR. CRAWFORD

TAMPA — Anorexia nervosa reduces bone mass and puts young women at risk for early onset of osteoporosis, just at the time when they should be building peak bone mass, Dr. Steven Crawford said at the annual meeting of the International Society for Clinical Densitometry.

Health consequences of anorexia nervosa can be severe. In addition to loss of bone density, the patient can suffer cardiovascular problems, muscle loss and weakness, severe dehydration, anemia, and leukopenia. Female patients with anorexia nervosa are amenorrheic. Anorexia nervosa leads to a sevenfold increase in fracture risk. Of adult women with anorexia nervosa, 38% have osteoporosis, and 50% have a bone mineral density (BMD) level below the fracture threshold.

The extent of bone damage is directly affected by the severity of malnutrition and the disease duration. Consequences are more severe when disease onset occurs during the time of peak bone development. Approximately 60% of total bone mass is attained in the growth spurt that normally occurs in adolescence, and skeletal growth essentially is complete by age 18.

“Bone mineral density is lower when anorexia nervosa begins in adolescence than when it occurs in adult life, even when the duration of illness is comparable,” said Dr. Crawford, a clinical psychiatrist at the Center for Eating Disorders, Sheppard Pratt Health System, Baltimore.

Pathophysiology of low bone density in anorexia nervosa results from multiple factors, including undernutrition, hypogonadism, altered levels of bone-essential hormones and growth factors, excessive exercise, and hypercortisolism, among others. Undernutrition in anorexia nervosa leads to decreased levels of the sex hormones critical for bone development.

Levels of insulinlike growth factor-I (IGF-I) and growth hormone normally increase during puberty, and stimulate bone anabolism. In anorexic patients, IGF-I levels decrease, and patients acquire growth hormone resistance. Lack of calcium may prevent bone remodeling normally stimulated by exercise, and hypogonadism may impair the function of osteocytes that normally are activated by exercise.

Low BMD occurs at all skeletal sites in patients with anorexia nervosa, affecting both trabecular and cortical bone.

In addition to decreased BMD, another factor that contributes to bone fragility in patients with anorexia nervosa is decreased bone size. Patients with anorexia nervosa develop smaller bones in the vertebral body and femoral neck, compared with normal patients.

Dr. Crawford recommends a routine bone density scan in all patients with anorexia nervosa at disease onset and at least every 2 years thereafter. Restoration of normal weight can improve BMD in anorexic patients, but bone loss may continue, with bone restoration taking at least 21 months. “One-third of women recovering weight continue to have BMD z scores more than two standard deviations below the mean,” said Dr. Crawford. Bisphosphonates are not approved for treatment of premenopausal women. Although adequate calcium and vitamin D intake should be provided to patients with anorexia nervosa, supplementation with calcium and vitamin does not increase BMD in anorexic patients. Some evidence suggests that a combination of twice-daily IGF-I administration and estrogen-progesterone treatment may be effective in increasing BMD in anorexic women. Androgen replacement studies have shown conflicting results.

Normally, patients with osteoporosis are advised to engage in weight-bearing exercise such as walking, stair climbing, and weight lifting. However, for patients with anorexia nervosa, the potential benefits of exercise might be offset by the risk of fractures, delayed weight gain, and exercise-induced amenorrhea. “In our program, we recommend 6 months of abstinence from exercise. Then we reintroduce activity into their lifestyle,” he said.

BMD 'is lower when anorexia nervosa begins in adolescence than when it occurs in adult life.' DR. CRAWFORD

TAMPA — Anorexia nervosa reduces bone mass and puts young women at risk for early onset of osteoporosis, just at the time when they should be building peak bone mass, Dr. Steven Crawford said at the annual meeting of the International Society for Clinical Densitometry.

Health consequences of anorexia nervosa can be severe. In addition to loss of bone density, the patient can suffer cardiovascular problems, muscle loss and weakness, severe dehydration, anemia, and leukopenia. Female patients with anorexia nervosa are amenorrheic. Anorexia nervosa leads to a sevenfold increase in fracture risk. Of adult women with anorexia nervosa, 38% have osteoporosis, and 50% have a bone mineral density (BMD) level below the fracture threshold.

The extent of bone damage is directly affected by the severity of malnutrition and the disease duration. Consequences are more severe when disease onset occurs during the time of peak bone development. Approximately 60% of total bone mass is attained in the growth spurt that normally occurs in adolescence, and skeletal growth essentially is complete by age 18.

“Bone mineral density is lower when anorexia nervosa begins in adolescence than when it occurs in adult life, even when the duration of illness is comparable,” said Dr. Crawford, a clinical psychiatrist at the Center for Eating Disorders, Sheppard Pratt Health System, Baltimore.

Pathophysiology of low bone density in anorexia nervosa results from multiple factors, including undernutrition, hypogonadism, altered levels of bone-essential hormones and growth factors, excessive exercise, and hypercortisolism, among others. Undernutrition in anorexia nervosa leads to decreased levels of the sex hormones critical for bone development.

Levels of insulinlike growth factor-I (IGF-I) and growth hormone normally increase during puberty, and stimulate bone anabolism. In anorexic patients, IGF-I levels decrease, and patients acquire growth hormone resistance. Lack of calcium may prevent bone remodeling normally stimulated by exercise, and hypogonadism may impair the function of osteocytes that normally are activated by exercise.

Low BMD occurs at all skeletal sites in patients with anorexia nervosa, affecting both trabecular and cortical bone.

In addition to decreased BMD, another factor that contributes to bone fragility in patients with anorexia nervosa is decreased bone size. Patients with anorexia nervosa develop smaller bones in the vertebral body and femoral neck, compared with normal patients.

Dr. Crawford recommends a routine bone density scan in all patients with anorexia nervosa at disease onset and at least every 2 years thereafter. Restoration of normal weight can improve BMD in anorexic patients, but bone loss may continue, with bone restoration taking at least 21 months. “One-third of women recovering weight continue to have BMD z scores more than two standard deviations below the mean,” said Dr. Crawford. Bisphosphonates are not approved for treatment of premenopausal women. Although adequate calcium and vitamin D intake should be provided to patients with anorexia nervosa, supplementation with calcium and vitamin does not increase BMD in anorexic patients. Some evidence suggests that a combination of twice-daily IGF-I administration and estrogen-progesterone treatment may be effective in increasing BMD in anorexic women. Androgen replacement studies have shown conflicting results.

Normally, patients with osteoporosis are advised to engage in weight-bearing exercise such as walking, stair climbing, and weight lifting. However, for patients with anorexia nervosa, the potential benefits of exercise might be offset by the risk of fractures, delayed weight gain, and exercise-induced amenorrhea. “In our program, we recommend 6 months of abstinence from exercise. Then we reintroduce activity into their lifestyle,” he said.

BMD 'is lower when anorexia nervosa begins in adolescence than when it occurs in adult life.' DR. CRAWFORD

TAMPA — Anorexia nervosa reduces bone mass and puts young women at risk for early onset of osteoporosis, just at the time when they should be building peak bone mass, Dr. Steven Crawford said at the annual meeting of the International Society for Clinical Densitometry.

Health consequences of anorexia nervosa can be severe. In addition to loss of bone density, the patient can suffer cardiovascular problems, muscle loss and weakness, severe dehydration, anemia, and leukopenia. Female patients with anorexia nervosa are amenorrheic. Anorexia nervosa leads to a sevenfold increase in fracture risk. Of adult women with anorexia nervosa, 38% have osteoporosis, and 50% have a bone mineral density (BMD) level below the fracture threshold.

The extent of bone damage is directly affected by the severity of malnutrition and the disease duration. Consequences are more severe when disease onset occurs during the time of peak bone development. Approximately 60% of total bone mass is attained in the growth spurt that normally occurs in adolescence, and skeletal growth essentially is complete by age 18.

“Bone mineral density is lower when anorexia nervosa begins in adolescence than when it occurs in adult life, even when the duration of illness is comparable,” said Dr. Crawford, a clinical psychiatrist at the Center for Eating Disorders, Sheppard Pratt Health System, Baltimore.

Pathophysiology of low bone density in anorexia nervosa results from multiple factors, including undernutrition, hypogonadism, altered levels of bone-essential hormones and growth factors, excessive exercise, and hypercortisolism, among others. Undernutrition in anorexia nervosa leads to decreased levels of the sex hormones critical for bone development.

Levels of insulinlike growth factor-I (IGF-I) and growth hormone normally increase during puberty, and stimulate bone anabolism. In anorexic patients, IGF-I levels decrease, and patients acquire growth hormone resistance. Lack of calcium may prevent bone remodeling normally stimulated by exercise, and hypogonadism may impair the function of osteocytes that normally are activated by exercise.

Low BMD occurs at all skeletal sites in patients with anorexia nervosa, affecting both trabecular and cortical bone.

In addition to decreased BMD, another factor that contributes to bone fragility in patients with anorexia nervosa is decreased bone size. Patients with anorexia nervosa develop smaller bones in the vertebral body and femoral neck, compared with normal patients.

Dr. Crawford recommends a routine bone density scan in all patients with anorexia nervosa at disease onset and at least every 2 years thereafter. Restoration of normal weight can improve BMD in anorexic patients, but bone loss may continue, with bone restoration taking at least 21 months. “One-third of women recovering weight continue to have BMD z scores more than two standard deviations below the mean,” said Dr. Crawford. Bisphosphonates are not approved for treatment of premenopausal women. Although adequate calcium and vitamin D intake should be provided to patients with anorexia nervosa, supplementation with calcium and vitamin does not increase BMD in anorexic patients. Some evidence suggests that a combination of twice-daily IGF-I administration and estrogen-progesterone treatment may be effective in increasing BMD in anorexic women. Androgen replacement studies have shown conflicting results.

Normally, patients with osteoporosis are advised to engage in weight-bearing exercise such as walking, stair climbing, and weight lifting. However, for patients with anorexia nervosa, the potential benefits of exercise might be offset by the risk of fractures, delayed weight gain, and exercise-induced amenorrhea. “In our program, we recommend 6 months of abstinence from exercise. Then we reintroduce activity into their lifestyle,” he said.

TAMPA — Spinal osteoarthritis can occur following osteoporotic end-plate perforation and can lead to a falsely high bone mineral density score, Dr. Sumiaki Okamoto of the Okamoto Clinic in Oita, Japan, and colleagues reported in a poster presentation at the annual meeting of the International Society of Clinical Densitometry.

Dr. Okamoto and colleagues analyzed the relationship between lumbar bone mineral density (BMD) scores and the presence of multiple perforations in vertebral end plates in postmenopausal women with osteoporosis and related secondary osteoarthritis (OA).

The study population consisted of postmenopausal women aged 45–85 as well as healthy premenopausal women who were aged 20–40. The majority of the postmenopausal women studied had both osteoporosis as well as spinal osteoarthritis.

At a single outpatient clinic in Oita, Japan, investigators performed 3-D helical CT scans on 1,240 spines.

Perforations were frequently seen in vertebral end plates in untreated postmenopausal female patients but rarely were observed in premenopausal women volunteers.

The perforations were first seen soon after menopause and increased in number over time. The ratio of perforations to vertebral end-plate area was significantly correlated with the number of years after menopause.

Dr. Okamoto and colleagues speculate that perforations might originate from the circulatory system, as blood vessels pierce the vertebral end plate to nourish the intervertebral disks.

If a disk is herniated and under pressure, the disk nucleus could escape though the perforations. This occurrence could account for the loss of the watery content of disk cartilage that is associated with osteoarthritis.

“Overadaptation” of bone after osteoporosis leads to formation of multiple Schmorl's nodes at fracture lines. Serial radiographs documented the growth of osteophytes after fresh fractures in one patient. In another patient, serial radiographs revealed the disappearance of prominent osteophytes after stabilization.

Fracture lines did not appear to be smooth in the 3-D images. Instead, the images showed mixtures of perforated indentations or Schmorl's nodes, which indicated expansion of the disk space together with convergence of the rims of the vertebrae.

“The finding suggests that disk herniation into the weakened vertebral body through the perforated end plates can cause osteoarthritis in the same manner as the lateral slippage of the disk,” wrote the investigators.

“What has conventionally been known as fish-shaped vertebral fractures may in fact be secondary to the herniation of the disk nucleus into the weakened vertebral body of the osteoporotic spine,” the researchers added.

In this situation, the osteoarthritic changes are due to the bone, rather than the cartilage, and result from overadaptation. The intervertebral space narrows and the osteophytes surrounding the vertebral end plates fuse.

“The unloaded vertebral end plates disappear rapidly when the surrounding osteophytes fuse together like a single pipe to support the load,” wrote the study investigators. Furthermore, sclerotic calcification or callus formation around the end-plate perforations adds to an erroneously high lumbar BMD score. “I find it intriguing to connect two common illnesses, such as spinal osteoporosis and fractures, with vertebral osteoarthritis,” Dr. Harold Rosen of Beth Israel Deaconess Medical Center in Boston said in an interview.

“However, further research needs to be done to support this assertion, such as finding that the BMD at sites other than the spine is low in patients with spine OA,” Dr. Rosen added.

TAMPA — Spinal osteoarthritis can occur following osteoporotic end-plate perforation and can lead to a falsely high bone mineral density score, Dr. Sumiaki Okamoto of the Okamoto Clinic in Oita, Japan, and colleagues reported in a poster presentation at the annual meeting of the International Society of Clinical Densitometry.

Dr. Okamoto and colleagues analyzed the relationship between lumbar bone mineral density (BMD) scores and the presence of multiple perforations in vertebral end plates in postmenopausal women with osteoporosis and related secondary osteoarthritis (OA).

The study population consisted of postmenopausal women aged 45–85 as well as healthy premenopausal women who were aged 20–40. The majority of the postmenopausal women studied had both osteoporosis as well as spinal osteoarthritis.

At a single outpatient clinic in Oita, Japan, investigators performed 3-D helical CT scans on 1,240 spines.

Perforations were frequently seen in vertebral end plates in untreated postmenopausal female patients but rarely were observed in premenopausal women volunteers.

The perforations were first seen soon after menopause and increased in number over time. The ratio of perforations to vertebral end-plate area was significantly correlated with the number of years after menopause.

Dr. Okamoto and colleagues speculate that perforations might originate from the circulatory system, as blood vessels pierce the vertebral end plate to nourish the intervertebral disks.

If a disk is herniated and under pressure, the disk nucleus could escape though the perforations. This occurrence could account for the loss of the watery content of disk cartilage that is associated with osteoarthritis.

“Overadaptation” of bone after osteoporosis leads to formation of multiple Schmorl's nodes at fracture lines. Serial radiographs documented the growth of osteophytes after fresh fractures in one patient. In another patient, serial radiographs revealed the disappearance of prominent osteophytes after stabilization.

Fracture lines did not appear to be smooth in the 3-D images. Instead, the images showed mixtures of perforated indentations or Schmorl's nodes, which indicated expansion of the disk space together with convergence of the rims of the vertebrae.

“The finding suggests that disk herniation into the weakened vertebral body through the perforated end plates can cause osteoarthritis in the same manner as the lateral slippage of the disk,” wrote the investigators.

“What has conventionally been known as fish-shaped vertebral fractures may in fact be secondary to the herniation of the disk nucleus into the weakened vertebral body of the osteoporotic spine,” the researchers added.

In this situation, the osteoarthritic changes are due to the bone, rather than the cartilage, and result from overadaptation. The intervertebral space narrows and the osteophytes surrounding the vertebral end plates fuse.

“The unloaded vertebral end plates disappear rapidly when the surrounding osteophytes fuse together like a single pipe to support the load,” wrote the study investigators. Furthermore, sclerotic calcification or callus formation around the end-plate perforations adds to an erroneously high lumbar BMD score. “I find it intriguing to connect two common illnesses, such as spinal osteoporosis and fractures, with vertebral osteoarthritis,” Dr. Harold Rosen of Beth Israel Deaconess Medical Center in Boston said in an interview.

“However, further research needs to be done to support this assertion, such as finding that the BMD at sites other than the spine is low in patients with spine OA,” Dr. Rosen added.

TAMPA — Spinal osteoarthritis can occur following osteoporotic end-plate perforation and can lead to a falsely high bone mineral density score, Dr. Sumiaki Okamoto of the Okamoto Clinic in Oita, Japan, and colleagues reported in a poster presentation at the annual meeting of the International Society of Clinical Densitometry.

Dr. Okamoto and colleagues analyzed the relationship between lumbar bone mineral density (BMD) scores and the presence of multiple perforations in vertebral end plates in postmenopausal women with osteoporosis and related secondary osteoarthritis (OA).

The study population consisted of postmenopausal women aged 45–85 as well as healthy premenopausal women who were aged 20–40. The majority of the postmenopausal women studied had both osteoporosis as well as spinal osteoarthritis.

At a single outpatient clinic in Oita, Japan, investigators performed 3-D helical CT scans on 1,240 spines.

Perforations were frequently seen in vertebral end plates in untreated postmenopausal female patients but rarely were observed in premenopausal women volunteers.

The perforations were first seen soon after menopause and increased in number over time. The ratio of perforations to vertebral end-plate area was significantly correlated with the number of years after menopause.

Dr. Okamoto and colleagues speculate that perforations might originate from the circulatory system, as blood vessels pierce the vertebral end plate to nourish the intervertebral disks.

If a disk is herniated and under pressure, the disk nucleus could escape though the perforations. This occurrence could account for the loss of the watery content of disk cartilage that is associated with osteoarthritis.

“Overadaptation” of bone after osteoporosis leads to formation of multiple Schmorl's nodes at fracture lines. Serial radiographs documented the growth of osteophytes after fresh fractures in one patient. In another patient, serial radiographs revealed the disappearance of prominent osteophytes after stabilization.

Fracture lines did not appear to be smooth in the 3-D images. Instead, the images showed mixtures of perforated indentations or Schmorl's nodes, which indicated expansion of the disk space together with convergence of the rims of the vertebrae.

“The finding suggests that disk herniation into the weakened vertebral body through the perforated end plates can cause osteoarthritis in the same manner as the lateral slippage of the disk,” wrote the investigators.

“What has conventionally been known as fish-shaped vertebral fractures may in fact be secondary to the herniation of the disk nucleus into the weakened vertebral body of the osteoporotic spine,” the researchers added.

In this situation, the osteoarthritic changes are due to the bone, rather than the cartilage, and result from overadaptation. The intervertebral space narrows and the osteophytes surrounding the vertebral end plates fuse.

“The unloaded vertebral end plates disappear rapidly when the surrounding osteophytes fuse together like a single pipe to support the load,” wrote the study investigators. Furthermore, sclerotic calcification or callus formation around the end-plate perforations adds to an erroneously high lumbar BMD score. “I find it intriguing to connect two common illnesses, such as spinal osteoporosis and fractures, with vertebral osteoarthritis,” Dr. Harold Rosen of Beth Israel Deaconess Medical Center in Boston said in an interview.

“However, further research needs to be done to support this assertion, such as finding that the BMD at sites other than the spine is low in patients with spine OA,” Dr. Rosen added.

WASHINGTON — Postmenopausal women with a prior fall or those 80 years of age or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, the investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a odds ratio of 1.5 for a future fall, based on a analysis of potential risk factors for falls among 66,134 women enrolled in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without a diagnosis of osteoporosis. They could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis-specific medication. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking if they'd had a fracture in the previous year.

The sample of women in this study responded to all of the surveys. At baseline, the average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

The researchers included a long list of potential risk factors. These included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking and alcohol use, early menopause, height loss, peripheral T score, personal history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, history of estrogen therapy, calcium supplementation, use of certain medications (oral corticosteroids, thyroid medication, an osteoporosis-specific drug), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, breast cancer, other cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

In addition, history of depression and of stroke increased the risk of falling by over 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The NORA study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall period. The gaps between surveys likely mean falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample. No data were collected on factors known to be associated with falls, such as prescription medications, environment, gait, balance, and muscle strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies and is a consultant for Merck & Co. Two of her collaborators are employees of Merck.

WASHINGTON — Postmenopausal women with a prior fall or those 80 years of age or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, the investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a odds ratio of 1.5 for a future fall, based on a analysis of potential risk factors for falls among 66,134 women enrolled in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without a diagnosis of osteoporosis. They could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis-specific medication. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking if they'd had a fracture in the previous year.

The sample of women in this study responded to all of the surveys. At baseline, the average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

The researchers included a long list of potential risk factors. These included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking and alcohol use, early menopause, height loss, peripheral T score, personal history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, history of estrogen therapy, calcium supplementation, use of certain medications (oral corticosteroids, thyroid medication, an osteoporosis-specific drug), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, breast cancer, other cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

In addition, history of depression and of stroke increased the risk of falling by over 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The NORA study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall period. The gaps between surveys likely mean falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample. No data were collected on factors known to be associated with falls, such as prescription medications, environment, gait, balance, and muscle strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies and is a consultant for Merck & Co. Two of her collaborators are employees of Merck.

WASHINGTON — Postmenopausal women with a prior fall or those 80 years of age or older have a significantly greater risk of a subsequent fall, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

Specifically, the investigators found that women with a prior fall had an odds ratio of 2.7 and those 80 years or older had a odds ratio of 1.5 for a future fall, based on a analysis of potential risk factors for falls among 66,134 women enrolled in the National Osteoporosis Risk Assessment (NORA) study, said Dr. Elizabeth Barrett-Connor, chief of epidemiology in the department of family and preventive medicine at the University of California at San Diego.

The NORA study enrolled over 200,000 community-dwelling, postmenopausal women between 1997 and 1999. Women had to be at least 50 years old without a diagnosis of osteoporosis. They could not have had a bone mineral density measurement in the previous year or be taking an osteoporosis-specific medication. At baseline, BMD was measured at the heel, forearm, or finger. The women were followed up at 1, 3, and 6 years with surveys asking if they'd had a fracture in the previous year.

The sample of women in this study responded to all of the surveys. At baseline, the average age was 63 years. Most (91%) were white. The average T score was −0.78. In all, 38% reported at least one fall in the past year.

The researchers included a long list of potential risk factors. These included age, body mass index, a self-rating of health as being poor/fair, functional limitations, smoking and alcohol use, early menopause, height loss, peripheral T score, personal history of fracture after age 45, maternal history of fracture and/or osteoporosis, first-degree relatives with a history of fracture, history of estrogen therapy, calcium supplementation, use of certain medications (oral corticosteroids, thyroid medication, an osteoporosis-specific drug), history of depression, osteoporosis self-knowledge, and self-report of a fall within the previous 12 months at the year 1 survey. They also included arthritis, coronary artery disease, hypertension, diabetes, kidney/liver disease, breast cancer, other cancers, memory problems, stroke, hyperthyroidism, hypothyroidism, epilepsy, poor vision, and poor hearing.

In addition, history of depression and of stroke increased the risk of falling by over 40%. An additional nine factors were identified that significantly increased fall risk by 9%–23%. The number of baseline risk factors was linearly associated with a risk of falling.

The NORA study has several limitations. First, participants were volunteers and may not be a representative sample. Second, falls were self-reported and limited to a 12-month recall period. The gaps between surveys likely mean falls were underreported. Longitudinal attrition resulted in a slightly younger and healthier analytic sample. No data were collected on factors known to be associated with falls, such as prescription medications, environment, gait, balance, and muscle strength. Lastly, the cause of falls was not known.

Dr. Barrett-Connor disclosed research support from several pharmaceutical companies and is a consultant for Merck & Co. Two of her collaborators are employees of Merck.