Osteoporosis

SEATTLE — Older adults in the general population have an elevated risk of fractures related to osteoporosis if they take certain antiepileptic drugs, according to a population-based analysis.

“Prior studies have shown that antiepileptic drugs [AEDs] are associated with an increased risk of bone loss and fractures,” presenting author Jane McChesney said at the annual meeting of the American Academy of Neurology. “However, population-based data assessing the association between AEDs and osteoporotic-related fractures are scarce.”

“This study found that AEDs, except for fatty acid derivatives, are associated with an increased risk of osteoporotic-related fractures in men and women over age 50,” Ms. McChesney said.

“This is concerning as many of these AEDs are not only used to manage epilepsy, but are also widely used in older adults for the treatment of neuropathic pain, headaches, and psychiatric conditions, to name a few,” she added.

In the study, Ms. McChesney, a nursing student at the University of Calgary, Alta., and her colleagues analyzed population-based data from the province of Manitoba for the years 1996–2004.

Individuals were included if they were at least 50 years of age and had continuous health care coverage during the study period. They were excluded if they had taken osteoprotective medications in the year before a fracture or were residents of long-term care facilities.

Fractures were ascertained from diagnostic codes and were limited to vertebral, wrist, and hip fractures that were not related to severe trauma, according to Ms. McChesney.

Using the fracture date as the index date, each older adult with a fracture was matched with three fracture-free older adults by age, sex, ethnicity, and number of comorbidities.

Use of AEDs, defined as dispensation of a prescription to the individual in the past 4 months, was assessed from a drug database containing virtually all pharmacy dispensations for the province.

Analyses were based on 15,792 older adults who had experienced a fracture and 47,289 older adults who had not, Ms. McChesney reported. Overall, 70% were female, 62% were aged 70 years or older, and 67% had three or more comorbidities.

Fractures most commonly occurred in the wrist (52%), followed by the hip (26%) and vertebrae (22%).

After adjustment for social and demographic characteristics, home care, and comorbidities known to affect fracture risk, older adults had elevated odds of fracture if they used carbamazepine (odds ratio, 1.9), clonazepam (1.3), gabapentin (1.6), phenobarbital (2.2), and phenytoin (2.1). In contrast, their odds were not elevated if they used valproic acid.

It remains unknown if osteoprotective agents are beneficial in this context, she acknowledged, and that would be an important focus of additional research.

“Future studies are needed to determine the individual effects of the newer AEDs on bone health in this age group and to elucidate the mechanism of this association,” she concluded.

Ms. McChesney reported that she had no disclosures to make in relation to the study.

SEATTLE — Older adults in the general population have an elevated risk of fractures related to osteoporosis if they take certain antiepileptic drugs, according to a population-based analysis.

“Prior studies have shown that antiepileptic drugs [AEDs] are associated with an increased risk of bone loss and fractures,” presenting author Jane McChesney said at the annual meeting of the American Academy of Neurology. “However, population-based data assessing the association between AEDs and osteoporotic-related fractures are scarce.”

“This study found that AEDs, except for fatty acid derivatives, are associated with an increased risk of osteoporotic-related fractures in men and women over age 50,” Ms. McChesney said.

“This is concerning as many of these AEDs are not only used to manage epilepsy, but are also widely used in older adults for the treatment of neuropathic pain, headaches, and psychiatric conditions, to name a few,” she added.

In the study, Ms. McChesney, a nursing student at the University of Calgary, Alta., and her colleagues analyzed population-based data from the province of Manitoba for the years 1996–2004.

Individuals were included if they were at least 50 years of age and had continuous health care coverage during the study period. They were excluded if they had taken osteoprotective medications in the year before a fracture or were residents of long-term care facilities.

Fractures were ascertained from diagnostic codes and were limited to vertebral, wrist, and hip fractures that were not related to severe trauma, according to Ms. McChesney.

Using the fracture date as the index date, each older adult with a fracture was matched with three fracture-free older adults by age, sex, ethnicity, and number of comorbidities.

Use of AEDs, defined as dispensation of a prescription to the individual in the past 4 months, was assessed from a drug database containing virtually all pharmacy dispensations for the province.

Analyses were based on 15,792 older adults who had experienced a fracture and 47,289 older adults who had not, Ms. McChesney reported. Overall, 70% were female, 62% were aged 70 years or older, and 67% had three or more comorbidities.

Fractures most commonly occurred in the wrist (52%), followed by the hip (26%) and vertebrae (22%).

After adjustment for social and demographic characteristics, home care, and comorbidities known to affect fracture risk, older adults had elevated odds of fracture if they used carbamazepine (odds ratio, 1.9), clonazepam (1.3), gabapentin (1.6), phenobarbital (2.2), and phenytoin (2.1). In contrast, their odds were not elevated if they used valproic acid.

It remains unknown if osteoprotective agents are beneficial in this context, she acknowledged, and that would be an important focus of additional research.

“Future studies are needed to determine the individual effects of the newer AEDs on bone health in this age group and to elucidate the mechanism of this association,” she concluded.

Ms. McChesney reported that she had no disclosures to make in relation to the study.

SEATTLE — Older adults in the general population have an elevated risk of fractures related to osteoporosis if they take certain antiepileptic drugs, according to a population-based analysis.

“Prior studies have shown that antiepileptic drugs [AEDs] are associated with an increased risk of bone loss and fractures,” presenting author Jane McChesney said at the annual meeting of the American Academy of Neurology. “However, population-based data assessing the association between AEDs and osteoporotic-related fractures are scarce.”

“This study found that AEDs, except for fatty acid derivatives, are associated with an increased risk of osteoporotic-related fractures in men and women over age 50,” Ms. McChesney said.

“This is concerning as many of these AEDs are not only used to manage epilepsy, but are also widely used in older adults for the treatment of neuropathic pain, headaches, and psychiatric conditions, to name a few,” she added.

In the study, Ms. McChesney, a nursing student at the University of Calgary, Alta., and her colleagues analyzed population-based data from the province of Manitoba for the years 1996–2004.

Individuals were included if they were at least 50 years of age and had continuous health care coverage during the study period. They were excluded if they had taken osteoprotective medications in the year before a fracture or were residents of long-term care facilities.

Fractures were ascertained from diagnostic codes and were limited to vertebral, wrist, and hip fractures that were not related to severe trauma, according to Ms. McChesney.

Using the fracture date as the index date, each older adult with a fracture was matched with three fracture-free older adults by age, sex, ethnicity, and number of comorbidities.

Use of AEDs, defined as dispensation of a prescription to the individual in the past 4 months, was assessed from a drug database containing virtually all pharmacy dispensations for the province.

Analyses were based on 15,792 older adults who had experienced a fracture and 47,289 older adults who had not, Ms. McChesney reported. Overall, 70% were female, 62% were aged 70 years or older, and 67% had three or more comorbidities.

Fractures most commonly occurred in the wrist (52%), followed by the hip (26%) and vertebrae (22%).

After adjustment for social and demographic characteristics, home care, and comorbidities known to affect fracture risk, older adults had elevated odds of fracture if they used carbamazepine (odds ratio, 1.9), clonazepam (1.3), gabapentin (1.6), phenobarbital (2.2), and phenytoin (2.1). In contrast, their odds were not elevated if they used valproic acid.

It remains unknown if osteoprotective agents are beneficial in this context, she acknowledged, and that would be an important focus of additional research.

“Future studies are needed to determine the individual effects of the newer AEDs on bone health in this age group and to elucidate the mechanism of this association,” she concluded.

Ms. McChesney reported that she had no disclosures to make in relation to the study.

WASHINGTON — Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.

After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Expected bone loss associated with natural progression generally would be about 0.5%–1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington, who with her colleagues performed a chart review of 104 women (mean age 58 years) who were taking the drugs for breast cancer for up to 2 years and were evaluated for bone health. Of these, 61 (58%) had osteopenia. Eleven patients were taking a bisphosphonate at baseline. They were followed for an additional year.

Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.

Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.

WASHINGTON — Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.

After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Expected bone loss associated with natural progression generally would be about 0.5%–1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington, who with her colleagues performed a chart review of 104 women (mean age 58 years) who were taking the drugs for breast cancer for up to 2 years and were evaluated for bone health. Of these, 61 (58%) had osteopenia. Eleven patients were taking a bisphosphonate at baseline. They were followed for an additional year.

Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.

Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.

WASHINGTON — Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.

After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Expected bone loss associated with natural progression generally would be about 0.5%–1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington, who with her colleagues performed a chart review of 104 women (mean age 58 years) who were taking the drugs for breast cancer for up to 2 years and were evaluated for bone health. Of these, 61 (58%) had osteopenia. Eleven patients were taking a bisphosphonate at baseline. They were followed for an additional year.

Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.

Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.

WASHINGTON — Take a serious look at the bone health of patients with celiac disease, Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York, advises.

Patients with this gastrointestinal disease have an increased risk of osteoporosis and fragility fractures because their intestines poorly absorb calcium and vitamin D, and the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Studies show that up to 50% of men, 40% of postmenopausal women, and 10% of premenopausal women with the disorder have osteoporosis, and up to 30% of these groups have osteopenia.

Yet only 6% of patients with celiac disease will have osteopenia or osteoporosis as their presenting symptom.

Antibodies against tissue transglutaminase (tTG), which contribute to the gluten intolerance that characterizes celiac disease, appear to have a deleterious effect on bone, said Dr. Green. “Tissue transglutaminase is a ubiquitous enzyme that is also present in bone.” Antibodies to tTG are also present in bone and emerging evidence suggests they impair active mineralization.

Studies have shown that a gluten-free diet, which decreases anti-tTG levels, directly correlates with increased bone mass in patients with celiac disease and low bone mineral density, he said at an international symposium sponsored by the National Osteoporosis Foundation.

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, he said. Comorbidities may also play a role. Secondary hyperparathyroidism is common in patients with celiac disease and may prevent patients from attaining their maximum bone density during childhood. Premature menopause in women and reduced gonadal function in men also can contribute to poor bone health, Dr. Green said.

Bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, he said. Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, he added.

WASHINGTON — Take a serious look at the bone health of patients with celiac disease, Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York, advises.

Patients with this gastrointestinal disease have an increased risk of osteoporosis and fragility fractures because their intestines poorly absorb calcium and vitamin D, and the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Studies show that up to 50% of men, 40% of postmenopausal women, and 10% of premenopausal women with the disorder have osteoporosis, and up to 30% of these groups have osteopenia.

Yet only 6% of patients with celiac disease will have osteopenia or osteoporosis as their presenting symptom.

Antibodies against tissue transglutaminase (tTG), which contribute to the gluten intolerance that characterizes celiac disease, appear to have a deleterious effect on bone, said Dr. Green. “Tissue transglutaminase is a ubiquitous enzyme that is also present in bone.” Antibodies to tTG are also present in bone and emerging evidence suggests they impair active mineralization.

Studies have shown that a gluten-free diet, which decreases anti-tTG levels, directly correlates with increased bone mass in patients with celiac disease and low bone mineral density, he said at an international symposium sponsored by the National Osteoporosis Foundation.

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, he said. Comorbidities may also play a role. Secondary hyperparathyroidism is common in patients with celiac disease and may prevent patients from attaining their maximum bone density during childhood. Premature menopause in women and reduced gonadal function in men also can contribute to poor bone health, Dr. Green said.

Bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, he said. Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, he added.

WASHINGTON — Take a serious look at the bone health of patients with celiac disease, Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York, advises.

Patients with this gastrointestinal disease have an increased risk of osteoporosis and fragility fractures because their intestines poorly absorb calcium and vitamin D, and the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Studies show that up to 50% of men, 40% of postmenopausal women, and 10% of premenopausal women with the disorder have osteoporosis, and up to 30% of these groups have osteopenia.

Yet only 6% of patients with celiac disease will have osteopenia or osteoporosis as their presenting symptom.

Antibodies against tissue transglutaminase (tTG), which contribute to the gluten intolerance that characterizes celiac disease, appear to have a deleterious effect on bone, said Dr. Green. “Tissue transglutaminase is a ubiquitous enzyme that is also present in bone.” Antibodies to tTG are also present in bone and emerging evidence suggests they impair active mineralization.

Studies have shown that a gluten-free diet, which decreases anti-tTG levels, directly correlates with increased bone mass in patients with celiac disease and low bone mineral density, he said at an international symposium sponsored by the National Osteoporosis Foundation.

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, he said. Comorbidities may also play a role. Secondary hyperparathyroidism is common in patients with celiac disease and may prevent patients from attaining their maximum bone density during childhood. Premature menopause in women and reduced gonadal function in men also can contribute to poor bone health, Dr. Green said.

Bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, he said. Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, he added.

The Food and Drug Administration has approved dosing the osteoporosis drug zoledronic acid (Reclast) once every 2 years for the prevention of bone loss in postmenopausal women, making it the first bisphosphonate in its class to get the nod for a 2-year indication.

The approval is based on results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention trial in which a single infusion of the zoledronic acid agent significantly increased bone mass relative to placebo at 2 years in postmenopausal women with osteopenia, according to a statement by the drug manufacturer, Novartis Pharmaceuticals Corp.

The 2-year double-blind, placebo-controlled study was presented in April at an international symposium sponsored by the National Osteoporosis Foundation in Washington by Dr. Chris Recknor.

HORIZON comprised 581 women aged 45 years and older with low bone mineral density (T scores of −1 to −2.5) who were randomized to receive one of three regimens: 5 mg zoledronic acid at study onset and at 1 year; 5 mg zoledronic acid at study onset and placebo at 1 year; or placebo at study onset and at 1 year. The subjects' mean age was 60 years. Most (93%) were white.

The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover.

Both of the Reclast treatment groups showed significantly increased BMD, compared with placebo. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo (see chart), reported Dr. Recknor, who is an internist specializing in osteoporosis in Gainesville, Ga.

Specifically, treatment with a single zoledronic acid infusion increased spine BMD by 6.3% among women in the early menopause group (within 5 years of menopause) and by 5.4% among those in the late menopause group, according Novartis's June 1 announcement of the new indication.

Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.

Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group, Dr. Recknor reported.

Already approved as a once-yearly infusion for the treatment of women with postmenopausal osteoporosis and men with osteoporosis, as well as for the treatment of Paget disease of bone and the prevention and treatment of glucocorticoid-induced osteoporosis, Reclast is now the first and only approved single-dose, biyearly infusion for the prevention postmenopausal osteoporosis, according to the Novartis statement.

At the osteoporosis symposium in April, Dr. Recknor said in an interview using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture.” Furthermore, the HORIZON results raise a tantalizing possibility. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

The less-frequent dosing is being touted as an advance by Dr. Mone Zaidi, director of the Mount Sinai Bone Program at Mount Sinai School of Medicine, New York, because of the convenience of biyearly treatment compared with daily, weekly, and monthly regimens.

“There were not many differences that were either statistically significant or clinically meaningful between the two treated groups in the [HORIZON] study. Once every 2 years is an excellent way to go forward, which would improve compliance in the early postmenopausal woman who rapidly loses bone,” he said in an interview after the Novartis's announcement of the new indication.

Another study presented at the osteoporosis symposium shed light on zoledronic acid's role in preventing bone loss in women who've already had a hip fracture.

A subanalysis of a second HORIZON study showed that zoledronic acid indeed benefits patients with a recent fracture—and particularly the very elderly and those with the poorest bone quality.

The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).

The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., who presented the trial data during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication.

“These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore.

“The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures due to continued bone loss,” said Dr. Orwig.

Novartis Pharmaceuticals Corp. sponsored the HORIZON studies. Dr. Orwig has received research funding from the company. Dr. Recknor and Dr. Zaidi are on the Novartis speakers bureau.

Diana Mahoney contributed to this report.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration has approved dosing the osteoporosis drug zoledronic acid (Reclast) once every 2 years for the prevention of bone loss in postmenopausal women, making it the first bisphosphonate in its class to get the nod for a 2-year indication.

The approval is based on results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention trial in which a single infusion of the zoledronic acid agent significantly increased bone mass relative to placebo at 2 years in postmenopausal women with osteopenia, according to a statement by the drug manufacturer, Novartis Pharmaceuticals Corp.

The 2-year double-blind, placebo-controlled study was presented in April at an international symposium sponsored by the National Osteoporosis Foundation in Washington by Dr. Chris Recknor.

HORIZON comprised 581 women aged 45 years and older with low bone mineral density (T scores of −1 to −2.5) who were randomized to receive one of three regimens: 5 mg zoledronic acid at study onset and at 1 year; 5 mg zoledronic acid at study onset and placebo at 1 year; or placebo at study onset and at 1 year. The subjects' mean age was 60 years. Most (93%) were white.

The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover.

Both of the Reclast treatment groups showed significantly increased BMD, compared with placebo. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo (see chart), reported Dr. Recknor, who is an internist specializing in osteoporosis in Gainesville, Ga.

Specifically, treatment with a single zoledronic acid infusion increased spine BMD by 6.3% among women in the early menopause group (within 5 years of menopause) and by 5.4% among those in the late menopause group, according Novartis's June 1 announcement of the new indication.

Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.

Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group, Dr. Recknor reported.

Already approved as a once-yearly infusion for the treatment of women with postmenopausal osteoporosis and men with osteoporosis, as well as for the treatment of Paget disease of bone and the prevention and treatment of glucocorticoid-induced osteoporosis, Reclast is now the first and only approved single-dose, biyearly infusion for the prevention postmenopausal osteoporosis, according to the Novartis statement.

At the osteoporosis symposium in April, Dr. Recknor said in an interview using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture.” Furthermore, the HORIZON results raise a tantalizing possibility. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

The less-frequent dosing is being touted as an advance by Dr. Mone Zaidi, director of the Mount Sinai Bone Program at Mount Sinai School of Medicine, New York, because of the convenience of biyearly treatment compared with daily, weekly, and monthly regimens.

“There were not many differences that were either statistically significant or clinically meaningful between the two treated groups in the [HORIZON] study. Once every 2 years is an excellent way to go forward, which would improve compliance in the early postmenopausal woman who rapidly loses bone,” he said in an interview after the Novartis's announcement of the new indication.

Another study presented at the osteoporosis symposium shed light on zoledronic acid's role in preventing bone loss in women who've already had a hip fracture.

A subanalysis of a second HORIZON study showed that zoledronic acid indeed benefits patients with a recent fracture—and particularly the very elderly and those with the poorest bone quality.

The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).

The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., who presented the trial data during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication.

“These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore.

“The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures due to continued bone loss,” said Dr. Orwig.

Novartis Pharmaceuticals Corp. sponsored the HORIZON studies. Dr. Orwig has received research funding from the company. Dr. Recknor and Dr. Zaidi are on the Novartis speakers bureau.

Diana Mahoney contributed to this report.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration has approved dosing the osteoporosis drug zoledronic acid (Reclast) once every 2 years for the prevention of bone loss in postmenopausal women, making it the first bisphosphonate in its class to get the nod for a 2-year indication.

The approval is based on results of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention trial in which a single infusion of the zoledronic acid agent significantly increased bone mass relative to placebo at 2 years in postmenopausal women with osteopenia, according to a statement by the drug manufacturer, Novartis Pharmaceuticals Corp.

The 2-year double-blind, placebo-controlled study was presented in April at an international symposium sponsored by the National Osteoporosis Foundation in Washington by Dr. Chris Recknor.

HORIZON comprised 581 women aged 45 years and older with low bone mineral density (T scores of −1 to −2.5) who were randomized to receive one of three regimens: 5 mg zoledronic acid at study onset and at 1 year; 5 mg zoledronic acid at study onset and placebo at 1 year; or placebo at study onset and at 1 year. The subjects' mean age was 60 years. Most (93%) were white.

The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover.

Both of the Reclast treatment groups showed significantly increased BMD, compared with placebo. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo (see chart), reported Dr. Recknor, who is an internist specializing in osteoporosis in Gainesville, Ga.

Specifically, treatment with a single zoledronic acid infusion increased spine BMD by 6.3% among women in the early menopause group (within 5 years of menopause) and by 5.4% among those in the late menopause group, according Novartis's June 1 announcement of the new indication.

Both zoledronic acid regimens showed significant reductions in bone turnover markers compared with placebo. Markers in the double-infusion group were significantly lower than those in the single-infusion group.

Adverse events were most commonly observed in the first 3 days after the first infusion, when they were significantly more common in both active groups (60% vs. 25%). The most frequently reported were pain, fever, chills, myalgia, nausea, and headache. Adverse events were significantly lower after the second infusion, occurring in 18% of the double-infusion group, 11% of the single-infusion group, and 12% of the placebo group, Dr. Recknor reported.

Already approved as a once-yearly infusion for the treatment of women with postmenopausal osteoporosis and men with osteoporosis, as well as for the treatment of Paget disease of bone and the prevention and treatment of glucocorticoid-induced osteoporosis, Reclast is now the first and only approved single-dose, biyearly infusion for the prevention postmenopausal osteoporosis, according to the Novartis statement.

At the osteoporosis symposium in April, Dr. Recknor said in an interview using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture.” Furthermore, the HORIZON results raise a tantalizing possibility. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

The less-frequent dosing is being touted as an advance by Dr. Mone Zaidi, director of the Mount Sinai Bone Program at Mount Sinai School of Medicine, New York, because of the convenience of biyearly treatment compared with daily, weekly, and monthly regimens.

“There were not many differences that were either statistically significant or clinically meaningful between the two treated groups in the [HORIZON] study. Once every 2 years is an excellent way to go forward, which would improve compliance in the early postmenopausal woman who rapidly loses bone,” he said in an interview after the Novartis's announcement of the new indication.

Another study presented at the osteoporosis symposium shed light on zoledronic acid's role in preventing bone loss in women who've already had a hip fracture.

A subanalysis of a second HORIZON study showed that zoledronic acid indeed benefits patients with a recent fracture—and particularly the very elderly and those with the poorest bone quality.

The HORIZON Recurrent Fracture Trial included 2,127 patients with a recent hip fracture who were randomized to an annual infusion of 5 mg zoledronic acid or placebo and followed for up to 5 years. HORIZON-RFT concluded that the drug reduced the rate of recurrent fracture by 35% (N. Engl. J. Med. 2007;357:1799–809).

The subanalysis examined response rates within specific patient groups, said Denise Orwig, Ph.D., who presented the trial data during a poster session at the meeting. The analysis showed that patients at the highest risk for a recurrent fracture—those who were at least 85 years old or who had a T score of less than −2.5 at the total hip—benefited the most from the treatment.

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication.

“These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore.

“The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures due to continued bone loss,” said Dr. Orwig.

Novartis Pharmaceuticals Corp. sponsored the HORIZON studies. Dr. Orwig has received research funding from the company. Dr. Recknor and Dr. Zaidi are on the Novartis speakers bureau.

Diana Mahoney contributed to this report.

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Further evidence that bisphosphonates do not really increase the risk of atrial fibrillation has come from an observational study involving more than 47,000 patients.

“We were unable to find an association between bisphosphonate therapy and atrial fibrillation. However, patients who received bisphosphonates were older and had more cardiovascular disease that we suspect accounts for the increased arrhythmia risk reported in other trials,” Dr. John D. Day reported at the annual meeting of the American College of Cardiology.

The study population comprised 37,485 enrollees in a Rocky Mountain health plan followed for an average of 4.6 years and 9,623 consecutive patients in a coronary angiography database with an average follow-up of 4 years.

The 7,489 health plan enrollees on bisphosphonate therapy for osteoporosis and fracture prevention had a 37% baseline prevalence of hyperlipidemia, significantly greater than the 30% rate among plan members not on a bisphosphonate. The bisphosphonate users were older, too. Yet their rates of new-onset atrial fibrillation, MI, and all-cause mortality during follow-up were no different than nonusers', according to Dr. Day of Intermountain Medical Center, Murray, Utah.

In the coronary angiography cohort, the patients on bisphosphonates were significantly older than were bisphosphonate nonusers, were more likely to be hypertensive by a margin of 56% to 45%, and had a 4.1% prevalence of heart failure compared with 0.7% in patients not on a bisphosphonate. A prior MI was present at baseline in 12.2% of bisphosphonate users and 4.8% of nonusers.

The all-cause mortality rate was 32.7% in bisphosphonate users in the angiography cohort and 18.8% in nonusers. Yet the rates of new-onset atrial fibrillation in the two groups were essentially the same: 10.2% among bisphosphonate users, 10.1% in nonusers.

In November 2008, the Food and Drug Administration reported that based on its review of the data from clinical trials involving nearly 40,000 patients treated with alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), zoledronic acid (Zometa), or placebo, there is “no clear association” between the use of drugs in this class and the rate of serious or nonserious atrial fibrillation. The FDA report concluded that physicians “should not alter their prescribing patterns for bisphosphonates.”

However, because of discordance among some of the studies, agency officials left the door open to possible future epidemiologic studies addressing the issue, prompting Dr. Day and coinvestigators to look at their patients' experience.

The FDA review was prompted by published reports of an apparent increase in serious atrial fibrillation events with zoledronic acid in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON) and with alendronate in the Fracture Intervention Trial (FIT) (N. Engl. J. Med. 2007;356:1809–22, 1895–6).

Dr. Day reported having no financial conflicts of interest relating to the study.

ORLANDO — Further evidence that bisphosphonates do not really increase the risk of atrial fibrillation has come from an observational study involving more than 47,000 patients.

“We were unable to find an association between bisphosphonate therapy and atrial fibrillation. However, patients who received bisphosphonates were older and had more cardiovascular disease that we suspect accounts for the increased arrhythmia risk reported in other trials,” Dr. John D. Day reported at the annual meeting of the American College of Cardiology.

The study population comprised 37,485 enrollees in a Rocky Mountain health plan followed for an average of 4.6 years and 9,623 consecutive patients in a coronary angiography database with an average follow-up of 4 years.

The 7,489 health plan enrollees on bisphosphonate therapy for osteoporosis and fracture prevention had a 37% baseline prevalence of hyperlipidemia, significantly greater than the 30% rate among plan members not on a bisphosphonate. The bisphosphonate users were older, too. Yet their rates of new-onset atrial fibrillation, MI, and all-cause mortality during follow-up were no different than nonusers', according to Dr. Day of Intermountain Medical Center, Murray, Utah.

In the coronary angiography cohort, the patients on bisphosphonates were significantly older than were bisphosphonate nonusers, were more likely to be hypertensive by a margin of 56% to 45%, and had a 4.1% prevalence of heart failure compared with 0.7% in patients not on a bisphosphonate. A prior MI was present at baseline in 12.2% of bisphosphonate users and 4.8% of nonusers.

The all-cause mortality rate was 32.7% in bisphosphonate users in the angiography cohort and 18.8% in nonusers. Yet the rates of new-onset atrial fibrillation in the two groups were essentially the same: 10.2% among bisphosphonate users, 10.1% in nonusers.

In November 2008, the Food and Drug Administration reported that based on its review of the data from clinical trials involving nearly 40,000 patients treated with alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), zoledronic acid (Zometa), or placebo, there is “no clear association” between the use of drugs in this class and the rate of serious or nonserious atrial fibrillation. The FDA report concluded that physicians “should not alter their prescribing patterns for bisphosphonates.”

However, because of discordance among some of the studies, agency officials left the door open to possible future epidemiologic studies addressing the issue, prompting Dr. Day and coinvestigators to look at their patients' experience.

The FDA review was prompted by published reports of an apparent increase in serious atrial fibrillation events with zoledronic acid in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON) and with alendronate in the Fracture Intervention Trial (FIT) (N. Engl. J. Med. 2007;356:1809–22, 1895–6).

Dr. Day reported having no financial conflicts of interest relating to the study.

ORLANDO — Further evidence that bisphosphonates do not really increase the risk of atrial fibrillation has come from an observational study involving more than 47,000 patients.

“We were unable to find an association between bisphosphonate therapy and atrial fibrillation. However, patients who received bisphosphonates were older and had more cardiovascular disease that we suspect accounts for the increased arrhythmia risk reported in other trials,” Dr. John D. Day reported at the annual meeting of the American College of Cardiology.

The study population comprised 37,485 enrollees in a Rocky Mountain health plan followed for an average of 4.6 years and 9,623 consecutive patients in a coronary angiography database with an average follow-up of 4 years.

The 7,489 health plan enrollees on bisphosphonate therapy for osteoporosis and fracture prevention had a 37% baseline prevalence of hyperlipidemia, significantly greater than the 30% rate among plan members not on a bisphosphonate. The bisphosphonate users were older, too. Yet their rates of new-onset atrial fibrillation, MI, and all-cause mortality during follow-up were no different than nonusers', according to Dr. Day of Intermountain Medical Center, Murray, Utah.

In the coronary angiography cohort, the patients on bisphosphonates were significantly older than were bisphosphonate nonusers, were more likely to be hypertensive by a margin of 56% to 45%, and had a 4.1% prevalence of heart failure compared with 0.7% in patients not on a bisphosphonate. A prior MI was present at baseline in 12.2% of bisphosphonate users and 4.8% of nonusers.

The all-cause mortality rate was 32.7% in bisphosphonate users in the angiography cohort and 18.8% in nonusers. Yet the rates of new-onset atrial fibrillation in the two groups were essentially the same: 10.2% among bisphosphonate users, 10.1% in nonusers.

In November 2008, the Food and Drug Administration reported that based on its review of the data from clinical trials involving nearly 40,000 patients treated with alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel), zoledronic acid (Zometa), or placebo, there is “no clear association” between the use of drugs in this class and the rate of serious or nonserious atrial fibrillation. The FDA report concluded that physicians “should not alter their prescribing patterns for bisphosphonates.”

However, because of discordance among some of the studies, agency officials left the door open to possible future epidemiologic studies addressing the issue, prompting Dr. Day and coinvestigators to look at their patients' experience.

The FDA review was prompted by published reports of an apparent increase in serious atrial fibrillation events with zoledronic acid in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON) and with alendronate in the Fracture Intervention Trial (FIT) (N. Engl. J. Med. 2007;356:1809–22, 1895–6).

Dr. Day reported having no financial conflicts of interest relating to the study.

NEW YORK — Treatment with a thiazolidinedione, either pioglitazone or rosiglitazone, was linked to an increased rate of bone fractures, particularly in women, in several recently published reports.

Although a definitive link between these drugs and an increased fracture risk has not yet been proved, the evidence amassed so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

“In those with a higher fracture risk, consider other hypoglycemic therapy,” advised Dr. Josse, professor of medicine and nutritional sciences at the University of Toronto and medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto. In addition, “if using a TZD, consider therapy to prevent TZD-induced osteoporosis.” Standard therapies for osteoporosis are effective in patients with diabetes—including those with diabetes who develop steroid-induced osteoporosis—but no data now exist on the efficacy of antiosteoporosis treatments for countering the possible effects of TZDs.

Reasonable steps to reduce the fracture risk in patients who must take a TZD include optimizing calcium intake and the supply of vitamin D, encouraging adequate exercise, and taking precautions to prevent falls. Administration of antiresorptive drugs, such as raloxifene and the bisphosphonates, seems to be effective in patients with diabetes, but the effects of bone anabolic drugs such as teriparatide in these patients isn't known.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from adverse-event reports from large, randomized, controlled trials; from a pair of small, randomized, controlled studies that specifically used bone density as an end point; and in two observational studies.

Perhaps the most persuasive evidence so far is a meta-analysis published in January that compiled adverse-event data from 10 randomized, controlled studies with a total of more than 13,000 patients, and also reviewed two observational studies with a total of more than 31,000 patients (Can. Med. Ass. J. 2009;180:32–9). In the 10 randomized trials, patients treated with a TZD had a statistically significant 45% increased risk for bone fracture, compared with patients in the control groups. When the analysis broke the study population down by sex, a statistically significant 2.2-fold increased fracture risk was seen in women treated with a TZD, but absolutely no increased risk was seen in men. Additional analysis by sex showed that, in women, TZD treatment was linked with significant reductions of bone mineral density in the lumbar spine and hip. The two observational studies also showed a significant link between TZD use and fracture risk in women, but not in men.

The two short-term, randomized studies included a study with 50 healthy postmenopausal women without osteoporosis or diabetes who were randomized to treatment with 8 mg rosiglitazone daily or placebo for 14 weeks. Despite the brief period of treatment, the women in the rosiglitazone-treated group had a statistically significant reduction in their total hip bone mineral density, compared with the placebo group (J. Clin. Endocrinol. Metab. 2007;92:1305–10). A second study, published last May, randomized 30 postmenopausal women with polycystic ovary syndrome but without diabetes to treatment with either 30 mg pioglitazone daily or placebo. After 16 weeks, the women treated with pioglitazone had significantly lower lumbar spine and femoral neck density, compared with the controls (J. Clin. Endocrinol. Metab. 2008;93:1696–701). The TZD-treated women also showed significantly decreased blood levels of bone-turnover hormones and enzymes.

Dr. Josse reported receiving research support from, and serving on the speakers bureau and advisory panel for, several companies including Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., and Sanofi-Aventis.

In patients with higher fracture risk, consider hypoglycemic therapy other than a TZD. DR. JOSSE

NEW YORK — Treatment with a thiazolidinedione, either pioglitazone or rosiglitazone, was linked to an increased rate of bone fractures, particularly in women, in several recently published reports.

Although a definitive link between these drugs and an increased fracture risk has not yet been proved, the evidence amassed so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

“In those with a higher fracture risk, consider other hypoglycemic therapy,” advised Dr. Josse, professor of medicine and nutritional sciences at the University of Toronto and medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto. In addition, “if using a TZD, consider therapy to prevent TZD-induced osteoporosis.” Standard therapies for osteoporosis are effective in patients with diabetes—including those with diabetes who develop steroid-induced osteoporosis—but no data now exist on the efficacy of antiosteoporosis treatments for countering the possible effects of TZDs.

Reasonable steps to reduce the fracture risk in patients who must take a TZD include optimizing calcium intake and the supply of vitamin D, encouraging adequate exercise, and taking precautions to prevent falls. Administration of antiresorptive drugs, such as raloxifene and the bisphosphonates, seems to be effective in patients with diabetes, but the effects of bone anabolic drugs such as teriparatide in these patients isn't known.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from adverse-event reports from large, randomized, controlled trials; from a pair of small, randomized, controlled studies that specifically used bone density as an end point; and in two observational studies.

Perhaps the most persuasive evidence so far is a meta-analysis published in January that compiled adverse-event data from 10 randomized, controlled studies with a total of more than 13,000 patients, and also reviewed two observational studies with a total of more than 31,000 patients (Can. Med. Ass. J. 2009;180:32–9). In the 10 randomized trials, patients treated with a TZD had a statistically significant 45% increased risk for bone fracture, compared with patients in the control groups. When the analysis broke the study population down by sex, a statistically significant 2.2-fold increased fracture risk was seen in women treated with a TZD, but absolutely no increased risk was seen in men. Additional analysis by sex showed that, in women, TZD treatment was linked with significant reductions of bone mineral density in the lumbar spine and hip. The two observational studies also showed a significant link between TZD use and fracture risk in women, but not in men.

The two short-term, randomized studies included a study with 50 healthy postmenopausal women without osteoporosis or diabetes who were randomized to treatment with 8 mg rosiglitazone daily or placebo for 14 weeks. Despite the brief period of treatment, the women in the rosiglitazone-treated group had a statistically significant reduction in their total hip bone mineral density, compared with the placebo group (J. Clin. Endocrinol. Metab. 2007;92:1305–10). A second study, published last May, randomized 30 postmenopausal women with polycystic ovary syndrome but without diabetes to treatment with either 30 mg pioglitazone daily or placebo. After 16 weeks, the women treated with pioglitazone had significantly lower lumbar spine and femoral neck density, compared with the controls (J. Clin. Endocrinol. Metab. 2008;93:1696–701). The TZD-treated women also showed significantly decreased blood levels of bone-turnover hormones and enzymes.

Dr. Josse reported receiving research support from, and serving on the speakers bureau and advisory panel for, several companies including Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., and Sanofi-Aventis.

In patients with higher fracture risk, consider hypoglycemic therapy other than a TZD. DR. JOSSE

NEW YORK — Treatment with a thiazolidinedione, either pioglitazone or rosiglitazone, was linked to an increased rate of bone fractures, particularly in women, in several recently published reports.

Although a definitive link between these drugs and an increased fracture risk has not yet been proved, the evidence amassed so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

“In those with a higher fracture risk, consider other hypoglycemic therapy,” advised Dr. Josse, professor of medicine and nutritional sciences at the University of Toronto and medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto. In addition, “if using a TZD, consider therapy to prevent TZD-induced osteoporosis.” Standard therapies for osteoporosis are effective in patients with diabetes—including those with diabetes who develop steroid-induced osteoporosis—but no data now exist on the efficacy of antiosteoporosis treatments for countering the possible effects of TZDs.

Reasonable steps to reduce the fracture risk in patients who must take a TZD include optimizing calcium intake and the supply of vitamin D, encouraging adequate exercise, and taking precautions to prevent falls. Administration of antiresorptive drugs, such as raloxifene and the bisphosphonates, seems to be effective in patients with diabetes, but the effects of bone anabolic drugs such as teriparatide in these patients isn't known.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from adverse-event reports from large, randomized, controlled trials; from a pair of small, randomized, controlled studies that specifically used bone density as an end point; and in two observational studies.

Perhaps the most persuasive evidence so far is a meta-analysis published in January that compiled adverse-event data from 10 randomized, controlled studies with a total of more than 13,000 patients, and also reviewed two observational studies with a total of more than 31,000 patients (Can. Med. Ass. J. 2009;180:32–9). In the 10 randomized trials, patients treated with a TZD had a statistically significant 45% increased risk for bone fracture, compared with patients in the control groups. When the analysis broke the study population down by sex, a statistically significant 2.2-fold increased fracture risk was seen in women treated with a TZD, but absolutely no increased risk was seen in men. Additional analysis by sex showed that, in women, TZD treatment was linked with significant reductions of bone mineral density in the lumbar spine and hip. The two observational studies also showed a significant link between TZD use and fracture risk in women, but not in men.

The two short-term, randomized studies included a study with 50 healthy postmenopausal women without osteoporosis or diabetes who were randomized to treatment with 8 mg rosiglitazone daily or placebo for 14 weeks. Despite the brief period of treatment, the women in the rosiglitazone-treated group had a statistically significant reduction in their total hip bone mineral density, compared with the placebo group (J. Clin. Endocrinol. Metab. 2007;92:1305–10). A second study, published last May, randomized 30 postmenopausal women with polycystic ovary syndrome but without diabetes to treatment with either 30 mg pioglitazone daily or placebo. After 16 weeks, the women treated with pioglitazone had significantly lower lumbar spine and femoral neck density, compared with the controls (J. Clin. Endocrinol. Metab. 2008;93:1696–701). The TZD-treated women also showed significantly decreased blood levels of bone-turnover hormones and enzymes.

Dr. Josse reported receiving research support from, and serving on the speakers bureau and advisory panel for, several companies including Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., and Sanofi-Aventis.

In patients with higher fracture risk, consider hypoglycemic therapy other than a TZD. DR. JOSSE

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to NIH (JAMA 2001;285:785–95).

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

In earlier studies, hrMRI showed that salmon-calcitonin nasal spray helped maintain trabecular microarchitecture, compared with placebo (J. Bone Miner. Res. 2005;20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women who were treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

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

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy.

“This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” Dr. Link said.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

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

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although the exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires very sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Trabecular and cortical bone architecture of the distal tibia is seen here with hr-pQCT.

High-resolution 3T MRI of the distal tibia visualizes trabecular and cortical bone architecture. Images courtesy Dr. Thomas M. Link

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to NIH (JAMA 2001;285:785–95).

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

In earlier studies, hrMRI showed that salmon-calcitonin nasal spray helped maintain trabecular microarchitecture, compared with placebo (J. Bone Miner. Res. 2005;20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women who were treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

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

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy.

“This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” Dr. Link said.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

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

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although the exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires very sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Trabecular and cortical bone architecture of the distal tibia is seen here with hr-pQCT.

High-resolution 3T MRI of the distal tibia visualizes trabecular and cortical bone architecture. Images courtesy Dr. Thomas M. Link

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to NIH (JAMA 2001;285:785–95).

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

In earlier studies, hrMRI showed that salmon-calcitonin nasal spray helped maintain trabecular microarchitecture, compared with placebo (J. Bone Miner. Res. 2005;20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women who were treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

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

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy.

“This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” Dr. Link said.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

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

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although the exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires very sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Trabecular and cortical bone architecture of the distal tibia is seen here with hr-pQCT.

High-resolution 3T MRI of the distal tibia visualizes trabecular and cortical bone architecture. Images courtesy Dr. Thomas M. Link

NEW YORK — Treatment with a thiazolidinedione, either pioglitazone or rosiglitazone, was linked to an increased rate of bone fractures, particularly in women, in several recently published reports.

Although a definitive link between these drugs and an increased fracture risk has not yet been proved, the evidence amassed so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

“In those with a higher fracture risk, consider other hypoglycemic therapy,” advised Dr. Josse, professor of medicine and nutritional sciences at the University of Toronto and medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto. In addition, “if using a TZD, consider therapy to prevent TZD-induced osteoporosis.” Standard therapies for osteoporosis are effective in patients with diabetes—including those with diabetes who develop steroid-induced osteoporosis—but no data now exist on the efficacy of antiosteoporosis treatments for countering the possible effects of TZDs, he noted.

Reasonable steps to reduce the fracture risk in patients who must take a TZD include optimizing calcium intake and the supply of vitamin D, encouraging adequate exercise, and taking precautions to prevent falls. Administration of antiresorptive drugs, such as raloxifene and the bisphosphonates, seems to be effective in patients with diabetes, but the effects of bone anabolic drugs such as teriparatide in these patients isn't known.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from some studies.

Perhaps the most persuasive evidence so far is a meta-analysis published in January that compiled adverse-event data from 10 randomized, controlled studies with a total of more than 13,000 patients, and also reviewed two observational studies with a total of more than 31,000 patients (Can. Med. Ass. J. 2009;180:32–9). In the 10 randomized trials, patients treated with a TZD had a statistically significant 45% increased risk for bone fracture, compared with patients in the control groups. When the analysis broke the study population down by sex, a statistically significant 2.2-fold increased fracture risk was seen in women treated with a TZD, but absolutely no increased risk was seen in men. Additional analysis by sex showed that, in women, TZD treatment was linked with significant reductions of bone mineral density in the lumbar spine and hip. The two observational studies also showed a significant link between TZD use and fracture risk in women, but not in men.

The two short-term, randomized studies included a study with 50 healthy postmenopausal women without osteoporosis or diabetes who were randomized to treatment with 8 mg rosiglitazone daily or placebo for 14 weeks. Despite the brief period of treatment, the women in the rosiglitazone-treated group had a statistically significant reduction in their total hip bone mineral density, compared with the placebo group (J. Clin. Endocrinol. Metab. 2007;92:1305–10). A second study, published last May, randomized 30 postmenopausal women with polycystic ovary syndrome but without diabetes to treatment with either 30 mg pioglitazone daily or placebo. After 16 weeks, the women treated with pioglitazone had significantly lower lumbar spine and femoral neck density, compared with the controls (J. Clin. Endocrinol. Metab. 2008;93:1696–701). The TZD-treated women also showed significantly decreased blood levels of bone-turnover hormones and enzymes.

Dr. Josse reported receiving research support from, and serving on the speakers bureau and advisory panel for, several companies including Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., and Sanofi-Aventis.

The evidence so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione. DR. JOSSE

NEW YORK — Treatment with a thiazolidinedione, either pioglitazone or rosiglitazone, was linked to an increased rate of bone fractures, particularly in women, in several recently published reports.

Although a definitive link between these drugs and an increased fracture risk has not yet been proved, the evidence amassed so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

“In those with a higher fracture risk, consider other hypoglycemic therapy,” advised Dr. Josse, professor of medicine and nutritional sciences at the University of Toronto and medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto. In addition, “if using a TZD, consider therapy to prevent TZD-induced osteoporosis.” Standard therapies for osteoporosis are effective in patients with diabetes—including those with diabetes who develop steroid-induced osteoporosis—but no data now exist on the efficacy of antiosteoporosis treatments for countering the possible effects of TZDs, he noted.

Reasonable steps to reduce the fracture risk in patients who must take a TZD include optimizing calcium intake and the supply of vitamin D, encouraging adequate exercise, and taking precautions to prevent falls. Administration of antiresorptive drugs, such as raloxifene and the bisphosphonates, seems to be effective in patients with diabetes, but the effects of bone anabolic drugs such as teriparatide in these patients isn't known.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from some studies.

Perhaps the most persuasive evidence so far is a meta-analysis published in January that compiled adverse-event data from 10 randomized, controlled studies with a total of more than 13,000 patients, and also reviewed two observational studies with a total of more than 31,000 patients (Can. Med. Ass. J. 2009;180:32–9). In the 10 randomized trials, patients treated with a TZD had a statistically significant 45% increased risk for bone fracture, compared with patients in the control groups. When the analysis broke the study population down by sex, a statistically significant 2.2-fold increased fracture risk was seen in women treated with a TZD, but absolutely no increased risk was seen in men. Additional analysis by sex showed that, in women, TZD treatment was linked with significant reductions of bone mineral density in the lumbar spine and hip. The two observational studies also showed a significant link between TZD use and fracture risk in women, but not in men.

The two short-term, randomized studies included a study with 50 healthy postmenopausal women without osteoporosis or diabetes who were randomized to treatment with 8 mg rosiglitazone daily or placebo for 14 weeks. Despite the brief period of treatment, the women in the rosiglitazone-treated group had a statistically significant reduction in their total hip bone mineral density, compared with the placebo group (J. Clin. Endocrinol. Metab. 2007;92:1305–10). A second study, published last May, randomized 30 postmenopausal women with polycystic ovary syndrome but without diabetes to treatment with either 30 mg pioglitazone daily or placebo. After 16 weeks, the women treated with pioglitazone had significantly lower lumbar spine and femoral neck density, compared with the controls (J. Clin. Endocrinol. Metab. 2008;93:1696–701). The TZD-treated women also showed significantly decreased blood levels of bone-turnover hormones and enzymes.

Dr. Josse reported receiving research support from, and serving on the speakers bureau and advisory panel for, several companies including Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., and Sanofi-Aventis.

The evidence so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione. DR. JOSSE

NEW YORK — Treatment with a thiazolidinedione, either pioglitazone or rosiglitazone, was linked to an increased rate of bone fractures, particularly in women, in several recently published reports.

Although a definitive link between these drugs and an increased fracture risk has not yet been proved, the evidence amassed so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

“In those with a higher fracture risk, consider other hypoglycemic therapy,” advised Dr. Josse, professor of medicine and nutritional sciences at the University of Toronto and medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto. In addition, “if using a TZD, consider therapy to prevent TZD-induced osteoporosis.” Standard therapies for osteoporosis are effective in patients with diabetes—including those with diabetes who develop steroid-induced osteoporosis—but no data now exist on the efficacy of antiosteoporosis treatments for countering the possible effects of TZDs, he noted.

Reasonable steps to reduce the fracture risk in patients who must take a TZD include optimizing calcium intake and the supply of vitamin D, encouraging adequate exercise, and taking precautions to prevent falls. Administration of antiresorptive drugs, such as raloxifene and the bisphosphonates, seems to be effective in patients with diabetes, but the effects of bone anabolic drugs such as teriparatide in these patients isn't known.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from some studies.

Perhaps the most persuasive evidence so far is a meta-analysis published in January that compiled adverse-event data from 10 randomized, controlled studies with a total of more than 13,000 patients, and also reviewed two observational studies with a total of more than 31,000 patients (Can. Med. Ass. J. 2009;180:32–9). In the 10 randomized trials, patients treated with a TZD had a statistically significant 45% increased risk for bone fracture, compared with patients in the control groups. When the analysis broke the study population down by sex, a statistically significant 2.2-fold increased fracture risk was seen in women treated with a TZD, but absolutely no increased risk was seen in men. Additional analysis by sex showed that, in women, TZD treatment was linked with significant reductions of bone mineral density in the lumbar spine and hip. The two observational studies also showed a significant link between TZD use and fracture risk in women, but not in men.

The two short-term, randomized studies included a study with 50 healthy postmenopausal women without osteoporosis or diabetes who were randomized to treatment with 8 mg rosiglitazone daily or placebo for 14 weeks. Despite the brief period of treatment, the women in the rosiglitazone-treated group had a statistically significant reduction in their total hip bone mineral density, compared with the placebo group (J. Clin. Endocrinol. Metab. 2007;92:1305–10). A second study, published last May, randomized 30 postmenopausal women with polycystic ovary syndrome but without diabetes to treatment with either 30 mg pioglitazone daily or placebo. After 16 weeks, the women treated with pioglitazone had significantly lower lumbar spine and femoral neck density, compared with the controls (J. Clin. Endocrinol. Metab. 2008;93:1696–701). The TZD-treated women also showed significantly decreased blood levels of bone-turnover hormones and enzymes.

Dr. Josse reported receiving research support from, and serving on the speakers bureau and advisory panel for, several companies including Amgen Inc., Eli Lilly & Co., Procter & Gamble Co., and Sanofi-Aventis.

The evidence so far is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione. DR. JOSSE

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to NIH (JAMA 2001;285:785–95).

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

In earlier studies, hrMRI showed that salmon-calcitonin nasal spray helped maintain trabecular microarchitecture, compared with placebo (J. Bone Miner. Res. 2005;20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women who were treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

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

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. “This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” said Dr. Link, who has has received research funding and support from Merck, which markets medication to treat osteoporosis.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

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

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although the exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires very sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Trabecular and cortical bone architecture of the distal tibia is seen here with hr-pQCT.

High-resolution 3T MRI of the distal tibia shows trabecular and cortical bone architecture. IMAGES COURTESY DR. THOMAS M. LINK

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to NIH (JAMA 2001;285:785–95).

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

In earlier studies, hrMRI showed that salmon-calcitonin nasal spray helped maintain trabecular microarchitecture, compared with placebo (J. Bone Miner. Res. 2005;20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women who were treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

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

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. “This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” said Dr. Link, who has has received research funding and support from Merck, which markets medication to treat osteoporosis.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

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

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although the exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires very sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Trabecular and cortical bone architecture of the distal tibia is seen here with hr-pQCT.

High-resolution 3T MRI of the distal tibia shows trabecular and cortical bone architecture. IMAGES COURTESY DR. THOMAS M. LINK

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to NIH (JAMA 2001;285:785–95).

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

In earlier studies, hrMRI showed that salmon-calcitonin nasal spray helped maintain trabecular microarchitecture, compared with placebo (J. Bone Miner. Res. 2005;20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women who were treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

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

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. “This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” said Dr. Link, who has has received research funding and support from Merck, which markets medication to treat osteoporosis.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

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

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although the exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires very sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Trabecular and cortical bone architecture of the distal tibia is seen here with hr-pQCT.

High-resolution 3T MRI of the distal tibia shows trabecular and cortical bone architecture. IMAGES COURTESY DR. THOMAS M. LINK

ORLANDO — The Framingham stroke risk score can predict a high-risk postmenopausal woman's likelihood of a future cerebrovascular event with raloxifene use.

Investigators in 26 countries enrolled 10,101 women at risk for a major coronary event in the Raloxifene for the Heart Study (RUTH). A total of 5,031 women had documented coronary heart disease and the remaining 5,070 had multiple coronary heart disease risk factors. Although overall stroke risk was not significantly different between women randomized to raloxifene versus placebo, a higher number of fatal stroke events occurred in the treatment group, 59, compared with 39 in the placebo group during a mean of 5.6 years follow-up.

To see how this increased risk associated with raloxifene (hazard ratio, 1.49; absolute risk increase, 0.7 per 1,000 woman-years) would apply to women stratified by baseline Framingham stroke scale score, David Cox, Ph.D., and colleague retrospectively calculated 10-year cumulative risk. They presented findings at the annual meeting of the North American Menopause Society. Eli Lilly & Co. supported the study, and Dr. Cox is a clinical research scientist for the company.

As expected, risks congregated in the third- and fourth-highest quartiles of Framingham score risk. However, there were no significant differences between treatment groups in either all strokes or nonfatal strokes, regardless of baseline Framingham score. Regarding fatal stroke, Dr. Cox said, “after 2 years, you start to see a split between placebo and raloxifene for risk of fatal stroke by Framingham stroke risk score in RUTH.” Specifically, women who scored a 13 or greater on the Framingham tool at baseline were at increased risk of stroke death.

ORLANDO — The Framingham stroke risk score can predict a high-risk postmenopausal woman's likelihood of a future cerebrovascular event with raloxifene use.

Investigators in 26 countries enrolled 10,101 women at risk for a major coronary event in the Raloxifene for the Heart Study (RUTH). A total of 5,031 women had documented coronary heart disease and the remaining 5,070 had multiple coronary heart disease risk factors. Although overall stroke risk was not significantly different between women randomized to raloxifene versus placebo, a higher number of fatal stroke events occurred in the treatment group, 59, compared with 39 in the placebo group during a mean of 5.6 years follow-up.

To see how this increased risk associated with raloxifene (hazard ratio, 1.49; absolute risk increase, 0.7 per 1,000 woman-years) would apply to women stratified by baseline Framingham stroke scale score, David Cox, Ph.D., and colleague retrospectively calculated 10-year cumulative risk. They presented findings at the annual meeting of the North American Menopause Society. Eli Lilly & Co. supported the study, and Dr. Cox is a clinical research scientist for the company.

As expected, risks congregated in the third- and fourth-highest quartiles of Framingham score risk. However, there were no significant differences between treatment groups in either all strokes or nonfatal strokes, regardless of baseline Framingham score. Regarding fatal stroke, Dr. Cox said, “after 2 years, you start to see a split between placebo and raloxifene for risk of fatal stroke by Framingham stroke risk score in RUTH.” Specifically, women who scored a 13 or greater on the Framingham tool at baseline were at increased risk of stroke death.

ORLANDO — The Framingham stroke risk score can predict a high-risk postmenopausal woman's likelihood of a future cerebrovascular event with raloxifene use.

Investigators in 26 countries enrolled 10,101 women at risk for a major coronary event in the Raloxifene for the Heart Study (RUTH). A total of 5,031 women had documented coronary heart disease and the remaining 5,070 had multiple coronary heart disease risk factors. Although overall stroke risk was not significantly different between women randomized to raloxifene versus placebo, a higher number of fatal stroke events occurred in the treatment group, 59, compared with 39 in the placebo group during a mean of 5.6 years follow-up.

To see how this increased risk associated with raloxifene (hazard ratio, 1.49; absolute risk increase, 0.7 per 1,000 woman-years) would apply to women stratified by baseline Framingham stroke scale score, David Cox, Ph.D., and colleague retrospectively calculated 10-year cumulative risk. They presented findings at the annual meeting of the North American Menopause Society. Eli Lilly & Co. supported the study, and Dr. Cox is a clinical research scientist for the company.

As expected, risks congregated in the third- and fourth-highest quartiles of Framingham score risk. However, there were no significant differences between treatment groups in either all strokes or nonfatal strokes, regardless of baseline Framingham score. Regarding fatal stroke, Dr. Cox said, “after 2 years, you start to see a split between placebo and raloxifene for risk of fatal stroke by Framingham stroke risk score in RUTH.” Specifically, women who scored a 13 or greater on the Framingham tool at baseline were at increased risk of stroke death.