Michele G. Sullivan

WASHINGTON — An investigational selective estrogen receptor modulator appears effective in increasing bone mineral density in postmenopausal women with normal or low bone mass.

The randomized, placebo-controlled phase III trial also concluded that the drug, arzoxifene, did not significantly increase endometrial thickness compared with placebo. However, a larger study is necessary to confirm uterine safety in women who were not prescreened for a normal uterus, Dr. Susan B. Broy said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Because selective estrogen receptor modulators (SERMs) have beneficial effects other than bone building, they may be an attractive alternative treatment for osteoporosis, Dr. Broy said in an interview. “The main advantage is that SERMs can prevent breast cancer. This is not yet proven for arzoxifene, since those trials are in progress, but it has been shown for other SERMS,” said Dr. Broy, a rheumatologist and professor of clinical medicine at the Chicago Medical School, North Chicago. “This makes SERMS attractive for the younger postmenopausal woman who could benefit from breast cancer prevention and osteoporosis prevention from one drug.”

SERMS have a shorter duration of action on bone than do bisphosphonates, and also cause fewer side effects, she added.

The 24-month study comprised 331 postmenopausal women whose bone mass was either normal or low (T-score 0 to −2.5). The subjects' mean age was 54 years. The cohort excluded women with vaginal bleeding, abnormal gynecologic findings, or an endometrial thickness of more than 5 mm.

Subjects were randomized to either 20 mg day arzoxifene or placebo. By 6 months, patients in the active group had gained a mean 1% in bone mineral density at the lumbar spine and in the total hip measurement, while there were no significant changes in BMD in placebo patients. By 12 months, active patients had gained a mean 2% at the lumbar spine and stayed steady at the total hip, while placebo patients had lost a mean of 0.5% at the lumbar spine and 0.25% at the total hip.

By 24 months, patients taking arzoxifene had maintained the mean 2% gain at the lumbar spine and the mean 1% gain at the total hip, while those taking placebo had lost a mean of 1.5% at both the lumbar spine and total hip.

Markers of bone turnover also improved significantly in the arzoxifene group compared with the placebo group at 24 months. The drug appeared to have no effect on endometrial hyperplasia or cancer. Endometrial thickness decreased by a mean of 0.191 mm in the placebo group and increased by a mean of 0.160 mm in the active group, not a significant difference.

Three percent of patients taking arzoxifene experienced a serious adverse event compared with 6% of those taking placebo. Hot flashes occurred in 12% of the active group and 11% of the placebo group. There were three cases of breast cancer in the placebo group and none in the active group.

Dr. Broy has been a speaker and consultant for Eli Lilly & Co., which conducted the trial.

WASHINGTON — An investigational selective estrogen receptor modulator appears effective in increasing bone mineral density in postmenopausal women with normal or low bone mass.

The randomized, placebo-controlled phase III trial also concluded that the drug, arzoxifene, did not significantly increase endometrial thickness compared with placebo. However, a larger study is necessary to confirm uterine safety in women who were not prescreened for a normal uterus, Dr. Susan B. Broy said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Because selective estrogen receptor modulators (SERMs) have beneficial effects other than bone building, they may be an attractive alternative treatment for osteoporosis, Dr. Broy said in an interview. “The main advantage is that SERMs can prevent breast cancer. This is not yet proven for arzoxifene, since those trials are in progress, but it has been shown for other SERMS,” said Dr. Broy, a rheumatologist and professor of clinical medicine at the Chicago Medical School, North Chicago. “This makes SERMS attractive for the younger postmenopausal woman who could benefit from breast cancer prevention and osteoporosis prevention from one drug.”

SERMS have a shorter duration of action on bone than do bisphosphonates, and also cause fewer side effects, she added.

The 24-month study comprised 331 postmenopausal women whose bone mass was either normal or low (T-score 0 to −2.5). The subjects' mean age was 54 years. The cohort excluded women with vaginal bleeding, abnormal gynecologic findings, or an endometrial thickness of more than 5 mm.

Subjects were randomized to either 20 mg day arzoxifene or placebo. By 6 months, patients in the active group had gained a mean 1% in bone mineral density at the lumbar spine and in the total hip measurement, while there were no significant changes in BMD in placebo patients. By 12 months, active patients had gained a mean 2% at the lumbar spine and stayed steady at the total hip, while placebo patients had lost a mean of 0.5% at the lumbar spine and 0.25% at the total hip.

By 24 months, patients taking arzoxifene had maintained the mean 2% gain at the lumbar spine and the mean 1% gain at the total hip, while those taking placebo had lost a mean of 1.5% at both the lumbar spine and total hip.

Markers of bone turnover also improved significantly in the arzoxifene group compared with the placebo group at 24 months. The drug appeared to have no effect on endometrial hyperplasia or cancer. Endometrial thickness decreased by a mean of 0.191 mm in the placebo group and increased by a mean of 0.160 mm in the active group, not a significant difference.

Three percent of patients taking arzoxifene experienced a serious adverse event compared with 6% of those taking placebo. Hot flashes occurred in 12% of the active group and 11% of the placebo group. There were three cases of breast cancer in the placebo group and none in the active group.

Dr. Broy has been a speaker and consultant for Eli Lilly & Co., which conducted the trial.

WASHINGTON — An investigational selective estrogen receptor modulator appears effective in increasing bone mineral density in postmenopausal women with normal or low bone mass.

The randomized, placebo-controlled phase III trial also concluded that the drug, arzoxifene, did not significantly increase endometrial thickness compared with placebo. However, a larger study is necessary to confirm uterine safety in women who were not prescreened for a normal uterus, Dr. Susan B. Broy said in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Because selective estrogen receptor modulators (SERMs) have beneficial effects other than bone building, they may be an attractive alternative treatment for osteoporosis, Dr. Broy said in an interview. “The main advantage is that SERMs can prevent breast cancer. This is not yet proven for arzoxifene, since those trials are in progress, but it has been shown for other SERMS,” said Dr. Broy, a rheumatologist and professor of clinical medicine at the Chicago Medical School, North Chicago. “This makes SERMS attractive for the younger postmenopausal woman who could benefit from breast cancer prevention and osteoporosis prevention from one drug.”

SERMS have a shorter duration of action on bone than do bisphosphonates, and also cause fewer side effects, she added.

The 24-month study comprised 331 postmenopausal women whose bone mass was either normal or low (T-score 0 to −2.5). The subjects' mean age was 54 years. The cohort excluded women with vaginal bleeding, abnormal gynecologic findings, or an endometrial thickness of more than 5 mm.

Subjects were randomized to either 20 mg day arzoxifene or placebo. By 6 months, patients in the active group had gained a mean 1% in bone mineral density at the lumbar spine and in the total hip measurement, while there were no significant changes in BMD in placebo patients. By 12 months, active patients had gained a mean 2% at the lumbar spine and stayed steady at the total hip, while placebo patients had lost a mean of 0.5% at the lumbar spine and 0.25% at the total hip.

By 24 months, patients taking arzoxifene had maintained the mean 2% gain at the lumbar spine and the mean 1% gain at the total hip, while those taking placebo had lost a mean of 1.5% at both the lumbar spine and total hip.

Markers of bone turnover also improved significantly in the arzoxifene group compared with the placebo group at 24 months. The drug appeared to have no effect on endometrial hyperplasia or cancer. Endometrial thickness decreased by a mean of 0.191 mm in the placebo group and increased by a mean of 0.160 mm in the active group, not a significant difference.

Three percent of patients taking arzoxifene experienced a serious adverse event compared with 6% of those taking placebo. Hot flashes occurred in 12% of the active group and 11% of the placebo group. There were three cases of breast cancer in the placebo group and none in the active group.

Dr. Broy has been a speaker and consultant for Eli Lilly & Co., which conducted the trial.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk. They are just not getting the message.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation. “There is apparently a worldwide problem with communicating these ideas to patients.”

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling from their physicians, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.”

Similarly, she said, those discussions should include information about how to mitigate risk factors. “Patients can take a number of steps to reduce their risk, such as not smoking, not drinking excessively, taking vitamin D and calcium every day, and taking bone-building medication as directed.”

Dr. Siris disclosed that she has receive consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk. They are just not getting the message.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation. “There is apparently a worldwide problem with communicating these ideas to patients.”

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling from their physicians, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.”

Similarly, she said, those discussions should include information about how to mitigate risk factors. “Patients can take a number of steps to reduce their risk, such as not smoking, not drinking excessively, taking vitamin D and calcium every day, and taking bone-building medication as directed.”

Dr. Siris disclosed that she has receive consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk. They are just not getting the message.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation. “There is apparently a worldwide problem with communicating these ideas to patients.”

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling from their physicians, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.”

Similarly, she said, those discussions should include information about how to mitigate risk factors. “Patients can take a number of steps to reduce their risk, such as not smoking, not drinking excessively, taking vitamin D and calcium every day, and taking bone-building medication as directed.”

Dr. Siris disclosed that she has receive consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

Children exposed to valproate in utero have significantly lower IQs at age 3 years than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator on the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor neurology of Emory University, Atlanta, and his associates reported a planned 3-year interim analysis in the New England Journal of Medicine (2009; 360:1597-605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most of the women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most of the children in the study (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate.

IQ scores were adjusted for factors that could significantly affect cognitive development.

Children exposed to valproate had a mean IQ of 92, the lowest any of the exposure groups and significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99.

In this analysis, only valproate maintained a significant dose-response relationship. In addition, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said.

The findings of both physical and cognitive problems with prenatal exposure show that the drug probably is not safe for use at any time during pregnancy, said Dr. Michael Privitera, director of the Cincinnati Epilepsy Center and another of the NEAD investigators.

“The neural tube defects [with which valproate is associated] occur during the first trimester, so there has been a question whether we might be able to use valproate later in pregnancy. This study shows that the answer is no, because cognitive development in the fetus occurs during the third trimester,” Dr. Privitera said in an interview.

“For some patients, valproate is the only medication that adequately controls seizures,” Dr. Meador and his colleagues wrote. “Such women should be informed of the potential risks associated with the use of this medication in pregnancy. If a woman taking valproate is already pregnant, it's critical that she not stop valproate without consultation with her physician.”

The risk of adverse fetal outcomes holds true for any woman who takes the drug during pregnancy, regardless of the indication, Dr. Meador said in the interview. “One other important point is that less than half of the prescriptions for valproate are for seizures or epilepsy. The majority are for pain or psychiatric indications.”

Children exposed to valproate in utero have significantly lower IQs at age 3 years than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator on the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor neurology of Emory University, Atlanta, and his associates reported a planned 3-year interim analysis in the New England Journal of Medicine (2009; 360:1597-605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most of the women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most of the children in the study (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate.

IQ scores were adjusted for factors that could significantly affect cognitive development.

Children exposed to valproate had a mean IQ of 92, the lowest any of the exposure groups and significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99.

In this analysis, only valproate maintained a significant dose-response relationship. In addition, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said.

The findings of both physical and cognitive problems with prenatal exposure show that the drug probably is not safe for use at any time during pregnancy, said Dr. Michael Privitera, director of the Cincinnati Epilepsy Center and another of the NEAD investigators.

“The neural tube defects [with which valproate is associated] occur during the first trimester, so there has been a question whether we might be able to use valproate later in pregnancy. This study shows that the answer is no, because cognitive development in the fetus occurs during the third trimester,” Dr. Privitera said in an interview.

“For some patients, valproate is the only medication that adequately controls seizures,” Dr. Meador and his colleagues wrote. “Such women should be informed of the potential risks associated with the use of this medication in pregnancy. If a woman taking valproate is already pregnant, it's critical that she not stop valproate without consultation with her physician.”

The risk of adverse fetal outcomes holds true for any woman who takes the drug during pregnancy, regardless of the indication, Dr. Meador said in the interview. “One other important point is that less than half of the prescriptions for valproate are for seizures or epilepsy. The majority are for pain or psychiatric indications.”

Children exposed to valproate in utero have significantly lower IQs at age 3 years than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator on the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor neurology of Emory University, Atlanta, and his associates reported a planned 3-year interim analysis in the New England Journal of Medicine (2009; 360:1597-605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most of the women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most of the children in the study (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate.

IQ scores were adjusted for factors that could significantly affect cognitive development.

Children exposed to valproate had a mean IQ of 92, the lowest any of the exposure groups and significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99.

In this analysis, only valproate maintained a significant dose-response relationship. In addition, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said.

The findings of both physical and cognitive problems with prenatal exposure show that the drug probably is not safe for use at any time during pregnancy, said Dr. Michael Privitera, director of the Cincinnati Epilepsy Center and another of the NEAD investigators.

“The neural tube defects [with which valproate is associated] occur during the first trimester, so there has been a question whether we might be able to use valproate later in pregnancy. This study shows that the answer is no, because cognitive development in the fetus occurs during the third trimester,” Dr. Privitera said in an interview.

“For some patients, valproate is the only medication that adequately controls seizures,” Dr. Meador and his colleagues wrote. “Such women should be informed of the potential risks associated with the use of this medication in pregnancy. If a woman taking valproate is already pregnant, it's critical that she not stop valproate without consultation with her physician.”

The risk of adverse fetal outcomes holds true for any woman who takes the drug during pregnancy, regardless of the indication, Dr. Meador said in the interview. “One other important point is that less than half of the prescriptions for valproate are for seizures or epilepsy. The majority are for pain or psychiatric indications.”

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation.

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.” Those discussions should include information about how to mitigate risk factors.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation.

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.” Those discussions should include information about how to mitigate risk factors.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

WASHINGTON — A majority of women susceptible to fragility fractures fail to appreciate those risks, even if they have been told by a physician that they have osteoporosis, a large international survey-based study has concluded.

“We found a remarkable failure of many women to perceive that these clear-cut factors are putting them at increased risk for a fracture,” said Dr. Ethel Siris, an investigator for GLOW (Global Longitudinal Study of Osteoporosis in Women). “It's really a critique of the medical profession. We have not adequately educated women that osteoporosis is a common disorder that increases future fracture risk.”

GLOW included more than 60,000 postmenopausal women who were recruited from 706 physician practices in 10 countries. The women completed questionnaires on demographic and medical information, risk factors for fragility fracture, any personal history of and treatment for osteoporosis, and health and functional status. Many of these questions were taken from the World Health Organization's Fracture Risk Assessment Tool (FRAX). A FRAX index score of 5 or more represents a 26% probability that a patient will experience a nonvertebral fracture within the next 5 years.

Comparing themselves with women of the same age, the majority of subjects with risk factors for fracture did not perceive themselves at increased risk, Dr. Siris said in an interview. “For example, 64% of women who had already had a fracture thought their risk of future fracture was lower than or the same as another woman of their age.”

Even more surprising, she said, 55% of women who had been told by a physician that they had osteoporosis thought that they were not at increased risk. “There was an obvious disconnect between knowing that they had the disorder and recognizing that it put them at increased risk of a fracture in the future,” she said. Of those with a FRAX index score of 5 or more, 75% also failed to identify themselves as being at high risk.

Women with other risk factors displayed a similar ignorance, Dr. Siris noted. Of women whose mother had experienced a hip fracture, 74% thought they were at a lower fracture risk than their peers or had a similar risk, as did 74% of those with a low body mass index, 80% of current smokers, 77% of those who frequently consumed alcohol, 61% of those taking corticosteroids, and 71% of those with rheumatoid arthritis.

The replies were consistent across countries, she said at an international symposium sponsored by the National Osteoporosis Foundation.

The failure to appreciate the implications of fracture risk may help account for the “lousy adherence” to osteoporosis therapy, said Dr. Siris, director of the osteoporosis center at Columbia University, New York. “People may simply just not comprehend the reason they are being treated.”

Patients clearly need more risk counseling, she said. “Bone health has to be something we, as doctors, pay constant attention to. And certainly as part of our discussions with patients, we need to collect information on risk factors and convey to patients that these factors do put them at increased risk for a fracture.” Those discussions should include information about how to mitigate risk factors.

Dr. Siris disclosed that she has received consulting fees for her time working on GLOW from Sanofi-Aventis and Procter & Gamble Co., which funded the project.

Benign positional vertigo appears to strongly correlate with osteopenia and osteoporosis in both men and women, researchers in a case-control study have concluded.

Compared to controls, patients with osteopenia were twice as likely to experience positional vertigo, and those with osteoporosis were three times as likely to experience the disorder, Dr. Ji Sook Kim and colleagues wrote.

“These findings suggest a deranged calcium metabolism in idiopathic benign positional vertigo,” Dr. Kim of the Seoul National University College of Medicine, Korea, said in an interview. “Restoring normal calcium metabolism may prevent recurrences” of BPV.

The study compared bone mineral density in 209 patients with a diagnosis of idiopathic benign positional vertigo (BPV) and 202 controls. Most of the patients (142) were female; their mean age was 60 years.

Among female patients, only 28% had normal bone mineral density, while 47% had osteopenia (T score greater than −2.5 and less than −1.0) and 25% had osteoporosis (T score = −2.5). Among female controls, normal bone mass was found in 57%; 33% had osteopenia and 9% had osteoporosis. (Percentages do not add up to 100% due to rounding.) The differences were significant at all points measured (Neurology 2009;72:1069-76).

In male patients, 48% had normal bone mass, while 40% had osteopenia and 12% had osteoporosis. Among male controls, 67% had normal bone mass, 27% had osteopenia, and 6% had osteoporosis. The differences were significant at the femur and first lumbar vertebra, but not at the other lumbar measurements.

Recurrent attacks of BPV (defined as at least two previous attacks at least 1 month apart) had occurred in 40% of patients. Compared to patients with new-onset BPV, patients with recurrent BPV were older (62 vs. 60 years) and more likely to be women (77% vs. 62%). A logistic regression analysis controlled for age, sex, smoking, and hyperphosphatemia; none of these variables represented a significant risk factor for BPV.

In women older than 45 years, the mean lowest T scores were lower in the recurrent group than in the new-onset group (−2.1 vs. −1.6). There were no between-group T-score differences in younger patients. This finding supports the premise that estrogen deficiency may contribute to the development of BPV by weakening the bond of otoconia to the utricle, the investigators wrote. In men, the weakening may be the result of bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

Benign positional vertigo appears to strongly correlate with osteopenia and osteoporosis in both men and women, researchers in a case-control study have concluded.

Compared to controls, patients with osteopenia were twice as likely to experience positional vertigo, and those with osteoporosis were three times as likely to experience the disorder, Dr. Ji Sook Kim and colleagues wrote.

“These findings suggest a deranged calcium metabolism in idiopathic benign positional vertigo,” Dr. Kim of the Seoul National University College of Medicine, Korea, said in an interview. “Restoring normal calcium metabolism may prevent recurrences” of BPV.

The study compared bone mineral density in 209 patients with a diagnosis of idiopathic benign positional vertigo (BPV) and 202 controls. Most of the patients (142) were female; their mean age was 60 years.

Among female patients, only 28% had normal bone mineral density, while 47% had osteopenia (T score greater than −2.5 and less than −1.0) and 25% had osteoporosis (T score = −2.5). Among female controls, normal bone mass was found in 57%; 33% had osteopenia and 9% had osteoporosis. (Percentages do not add up to 100% due to rounding.) The differences were significant at all points measured (Neurology 2009;72:1069-76).

In male patients, 48% had normal bone mass, while 40% had osteopenia and 12% had osteoporosis. Among male controls, 67% had normal bone mass, 27% had osteopenia, and 6% had osteoporosis. The differences were significant at the femur and first lumbar vertebra, but not at the other lumbar measurements.

Recurrent attacks of BPV (defined as at least two previous attacks at least 1 month apart) had occurred in 40% of patients. Compared to patients with new-onset BPV, patients with recurrent BPV were older (62 vs. 60 years) and more likely to be women (77% vs. 62%). A logistic regression analysis controlled for age, sex, smoking, and hyperphosphatemia; none of these variables represented a significant risk factor for BPV.

In women older than 45 years, the mean lowest T scores were lower in the recurrent group than in the new-onset group (−2.1 vs. −1.6). There were no between-group T-score differences in younger patients. This finding supports the premise that estrogen deficiency may contribute to the development of BPV by weakening the bond of otoconia to the utricle, the investigators wrote. In men, the weakening may be the result of bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

Benign positional vertigo appears to strongly correlate with osteopenia and osteoporosis in both men and women, researchers in a case-control study have concluded.

Compared to controls, patients with osteopenia were twice as likely to experience positional vertigo, and those with osteoporosis were three times as likely to experience the disorder, Dr. Ji Sook Kim and colleagues wrote.

“These findings suggest a deranged calcium metabolism in idiopathic benign positional vertigo,” Dr. Kim of the Seoul National University College of Medicine, Korea, said in an interview. “Restoring normal calcium metabolism may prevent recurrences” of BPV.

The study compared bone mineral density in 209 patients with a diagnosis of idiopathic benign positional vertigo (BPV) and 202 controls. Most of the patients (142) were female; their mean age was 60 years.

Among female patients, only 28% had normal bone mineral density, while 47% had osteopenia (T score greater than −2.5 and less than −1.0) and 25% had osteoporosis (T score = −2.5). Among female controls, normal bone mass was found in 57%; 33% had osteopenia and 9% had osteoporosis. (Percentages do not add up to 100% due to rounding.) The differences were significant at all points measured (Neurology 2009;72:1069-76).

In male patients, 48% had normal bone mass, while 40% had osteopenia and 12% had osteoporosis. Among male controls, 67% had normal bone mass, 27% had osteopenia, and 6% had osteoporosis. The differences were significant at the femur and first lumbar vertebra, but not at the other lumbar measurements.

Recurrent attacks of BPV (defined as at least two previous attacks at least 1 month apart) had occurred in 40% of patients. Compared to patients with new-onset BPV, patients with recurrent BPV were older (62 vs. 60 years) and more likely to be women (77% vs. 62%). A logistic regression analysis controlled for age, sex, smoking, and hyperphosphatemia; none of these variables represented a significant risk factor for BPV.

In women older than 45 years, the mean lowest T scores were lower in the recurrent group than in the new-onset group (−2.1 vs. −1.6). There were no between-group T-score differences in younger patients. This finding supports the premise that estrogen deficiency may contribute to the development of BPV by weakening the bond of otoconia to the utricle, the investigators wrote. In men, the weakening may be the result of bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

Routinely administering eptifibatide before angiography confers no survival benefit in patients with non-ST-segment elevation acute coronary syndromes, nor does early use reduce the number of subsequent heart attacks, compared with the use of eptifibatide after angiography, a large randomized controlled trial has concluded.

Further, early eptifibatide use, compared with delayed use, also carries a significantly increased risk for major bleeding, Dr. L. Kristin Newby said at a press teleconference during the annual meeting of the American College of Cardiology.

Guidelines in North America and Europe vary in their recommendations regarding early versus delayed provisional treatment with eptifibatide and other glycoprotein IIb/IIIa inhibitors, said Dr. Newby of Duke University Medical Center, Durham, N.C. Treatment decisions are usually guided by clinician preference or hospital policy. But the results of the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial may be strong enough to warrant a recommendation by the American College of Cardiology, she said. “I believe the guidelines committee will have to carefully consider these findings.”

EARLY ACS included 9,492 patients who had acute coronary syndrome without ST-segment elevation and were scheduled for an invasive intervention. Patients were assigned to one of two eptifibatide regimens. Early use consisted of two boluses of eptifibatide (180 mcg/kg of body weight each) given 10 minutes apart at least 12 hours before angiography and followed by a standard infusion. Delayed provisional use consisted of a matching placebo infusion with provisional use of eptifibatide after angiography.

The primary end points were a composite of all-cause mortality, heart attack, and recurrent ischemia requiring urgent revascularization, or a thrombotic complication during percutaneous coronary intervention within 96 hours. The secondary end point was a composite of death or heart attack within 30 days (N. Engl. J. Med. 2009; Mar. 30 [doi 10.1056/NEJMoa0901316

The patients' median age was 67 years. The median time from presentation of symptoms to randomization was almost 6 hours. Almost all (98%) underwent coronary angiography, and 59% later underwent PCI.

Compared with delayed administration, early administration of eptifibatide was not associated with any significant reduction in the composite primary end point (10.0% vs. 9.3%, respectively), or in the secondary end points of death or heart attack at 30 days (12.3% vs. 11.2%).

There were no significant differences between the groups in death from any cause; in the combination of death, heart attack, or urgent revascularization; or in any of the individual end points.

When bleeding severity was rated according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria, there was significantly more moderate bleeding in the early-administration group than in the delayed-administration group (6.8% vs. 4.3%; odds ratio, 1.6). When both severe and moderate bleeding were considered, the early strategy also carried a significantly increased risk (5.1% vs. 2.7%; OR, 1.9). Patients in the early administration group also required significantly more transfusions of packed red cells (8.6% vs. 6.7%; OR, 1.3). Dr. Newby said the EARLY ACS investigators are reviewing their data to identify subgroups of patients who have a low risk of bleeding and might benefit from early eptifibatide. “So far, we've seen no statistically significant interactions in our subgroup analyses, but we have seen some hints that patients who are troponin positive might get some benefit.”

Dr. Marc Cohen, professor of cardiology at Mount Sinai School of Medicine, New York, said, “I think it is fair to say that certain subgroups within the study may have diluted an otherwise important benefit from being observed. Specifically, the subgroup that was troponin negative—a group that we know from the year of the flood is not benefited with glycoprotein IIb/IIIa inhibitors—was not benefited in the EARLY-ACS trial and may have pulled the point estimate toward the neutral zone.

“In summary, I have to acknowledge that routine upstream administration of eptifibatide in high-risk, unstable angina or NSTEMI patients is not supported. I feel that several protocol-related variables may have contributed to a dilution of a beneficial effect,” he said.

The study was funded by Schering-Plough Corp. and Millennium Pharmaceuticals. Dr. Newby disclosed receiving grant support from Schering-Plough, and some of her coinvestigators disclosed that they receive some financial support from Schering-Plough.

Dr. Cohen said that he had no conflicts to disclose in regard to this study.

Routinely administering eptifibatide before angiography confers no survival benefit in patients with non-ST-segment elevation acute coronary syndromes, nor does early use reduce the number of subsequent heart attacks, compared with the use of eptifibatide after angiography, a large randomized controlled trial has concluded.

Further, early eptifibatide use, compared with delayed use, also carries a significantly increased risk for major bleeding, Dr. L. Kristin Newby said at a press teleconference during the annual meeting of the American College of Cardiology.

Guidelines in North America and Europe vary in their recommendations regarding early versus delayed provisional treatment with eptifibatide and other glycoprotein IIb/IIIa inhibitors, said Dr. Newby of Duke University Medical Center, Durham, N.C. Treatment decisions are usually guided by clinician preference or hospital policy. But the results of the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial may be strong enough to warrant a recommendation by the American College of Cardiology, she said. “I believe the guidelines committee will have to carefully consider these findings.”

EARLY ACS included 9,492 patients who had acute coronary syndrome without ST-segment elevation and were scheduled for an invasive intervention. Patients were assigned to one of two eptifibatide regimens. Early use consisted of two boluses of eptifibatide (180 mcg/kg of body weight each) given 10 minutes apart at least 12 hours before angiography and followed by a standard infusion. Delayed provisional use consisted of a matching placebo infusion with provisional use of eptifibatide after angiography.

The primary end points were a composite of all-cause mortality, heart attack, and recurrent ischemia requiring urgent revascularization, or a thrombotic complication during percutaneous coronary intervention within 96 hours. The secondary end point was a composite of death or heart attack within 30 days (N. Engl. J. Med. 2009; Mar. 30 [doi 10.1056/NEJMoa0901316

The patients' median age was 67 years. The median time from presentation of symptoms to randomization was almost 6 hours. Almost all (98%) underwent coronary angiography, and 59% later underwent PCI.

Compared with delayed administration, early administration of eptifibatide was not associated with any significant reduction in the composite primary end point (10.0% vs. 9.3%, respectively), or in the secondary end points of death or heart attack at 30 days (12.3% vs. 11.2%).

There were no significant differences between the groups in death from any cause; in the combination of death, heart attack, or urgent revascularization; or in any of the individual end points.

When bleeding severity was rated according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria, there was significantly more moderate bleeding in the early-administration group than in the delayed-administration group (6.8% vs. 4.3%; odds ratio, 1.6). When both severe and moderate bleeding were considered, the early strategy also carried a significantly increased risk (5.1% vs. 2.7%; OR, 1.9). Patients in the early administration group also required significantly more transfusions of packed red cells (8.6% vs. 6.7%; OR, 1.3). Dr. Newby said the EARLY ACS investigators are reviewing their data to identify subgroups of patients who have a low risk of bleeding and might benefit from early eptifibatide. “So far, we've seen no statistically significant interactions in our subgroup analyses, but we have seen some hints that patients who are troponin positive might get some benefit.”

Dr. Marc Cohen, professor of cardiology at Mount Sinai School of Medicine, New York, said, “I think it is fair to say that certain subgroups within the study may have diluted an otherwise important benefit from being observed. Specifically, the subgroup that was troponin negative—a group that we know from the year of the flood is not benefited with glycoprotein IIb/IIIa inhibitors—was not benefited in the EARLY-ACS trial and may have pulled the point estimate toward the neutral zone.

“In summary, I have to acknowledge that routine upstream administration of eptifibatide in high-risk, unstable angina or NSTEMI patients is not supported. I feel that several protocol-related variables may have contributed to a dilution of a beneficial effect,” he said.

The study was funded by Schering-Plough Corp. and Millennium Pharmaceuticals. Dr. Newby disclosed receiving grant support from Schering-Plough, and some of her coinvestigators disclosed that they receive some financial support from Schering-Plough.

Dr. Cohen said that he had no conflicts to disclose in regard to this study.

Routinely administering eptifibatide before angiography confers no survival benefit in patients with non-ST-segment elevation acute coronary syndromes, nor does early use reduce the number of subsequent heart attacks, compared with the use of eptifibatide after angiography, a large randomized controlled trial has concluded.

Further, early eptifibatide use, compared with delayed use, also carries a significantly increased risk for major bleeding, Dr. L. Kristin Newby said at a press teleconference during the annual meeting of the American College of Cardiology.

Guidelines in North America and Europe vary in their recommendations regarding early versus delayed provisional treatment with eptifibatide and other glycoprotein IIb/IIIa inhibitors, said Dr. Newby of Duke University Medical Center, Durham, N.C. Treatment decisions are usually guided by clinician preference or hospital policy. But the results of the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial may be strong enough to warrant a recommendation by the American College of Cardiology, she said. “I believe the guidelines committee will have to carefully consider these findings.”

EARLY ACS included 9,492 patients who had acute coronary syndrome without ST-segment elevation and were scheduled for an invasive intervention. Patients were assigned to one of two eptifibatide regimens. Early use consisted of two boluses of eptifibatide (180 mcg/kg of body weight each) given 10 minutes apart at least 12 hours before angiography and followed by a standard infusion. Delayed provisional use consisted of a matching placebo infusion with provisional use of eptifibatide after angiography.

The primary end points were a composite of all-cause mortality, heart attack, and recurrent ischemia requiring urgent revascularization, or a thrombotic complication during percutaneous coronary intervention within 96 hours. The secondary end point was a composite of death or heart attack within 30 days (N. Engl. J. Med. 2009; Mar. 30 [doi 10.1056/NEJMoa0901316

The patients' median age was 67 years. The median time from presentation of symptoms to randomization was almost 6 hours. Almost all (98%) underwent coronary angiography, and 59% later underwent PCI.

Compared with delayed administration, early administration of eptifibatide was not associated with any significant reduction in the composite primary end point (10.0% vs. 9.3%, respectively), or in the secondary end points of death or heart attack at 30 days (12.3% vs. 11.2%).

There were no significant differences between the groups in death from any cause; in the combination of death, heart attack, or urgent revascularization; or in any of the individual end points.

When bleeding severity was rated according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria, there was significantly more moderate bleeding in the early-administration group than in the delayed-administration group (6.8% vs. 4.3%; odds ratio, 1.6). When both severe and moderate bleeding were considered, the early strategy also carried a significantly increased risk (5.1% vs. 2.7%; OR, 1.9). Patients in the early administration group also required significantly more transfusions of packed red cells (8.6% vs. 6.7%; OR, 1.3). Dr. Newby said the EARLY ACS investigators are reviewing their data to identify subgroups of patients who have a low risk of bleeding and might benefit from early eptifibatide. “So far, we've seen no statistically significant interactions in our subgroup analyses, but we have seen some hints that patients who are troponin positive might get some benefit.”

Dr. Marc Cohen, professor of cardiology at Mount Sinai School of Medicine, New York, said, “I think it is fair to say that certain subgroups within the study may have diluted an otherwise important benefit from being observed. Specifically, the subgroup that was troponin negative—a group that we know from the year of the flood is not benefited with glycoprotein IIb/IIIa inhibitors—was not benefited in the EARLY-ACS trial and may have pulled the point estimate toward the neutral zone.

“In summary, I have to acknowledge that routine upstream administration of eptifibatide in high-risk, unstable angina or NSTEMI patients is not supported. I feel that several protocol-related variables may have contributed to a dilution of a beneficial effect,” he said.

The study was funded by Schering-Plough Corp. and Millennium Pharmaceuticals. Dr. Newby disclosed receiving grant support from Schering-Plough, and some of her coinvestigators disclosed that they receive some financial support from Schering-Plough.

Dr. Cohen said that he had no conflicts to disclose in regard to this study.

Children exposed to valproate in utero have significantly lower IQs at age 3 than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator on the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor of neurology, Emory University, Atlanta, and his associates reported a planned 3-year interim analysis (N. Engl. J. Med. 2009;360:1597–605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most children (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate.

IQ scores were adjusted for factors that could significantly affect cognitive development, some of which were maternal IQ, age at delivery, education, type of epilepsy, and seizure frequency.

Children exposed to valproate had the lowest mean IQs of any of the exposure groups (92)—significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99. These did not vary significantly from one another.

The association of valproate with reduced IQ held after adjustment for confounders in both a linear regression and subgroup analysis, the investigators said.

They also examined whether the IQ scores were related to AED dosage. In this analysis, only valproate maintained a significant dose-response relationship. Additionally, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said. A Finnish study reported a mean reduction of 13 points in verbal IQ in valproate-exposed children, compared with controls. A British study found that valproate exposure increased developmental delays, increased special education needs, and reduced verbal IQ, compared with unexposed children and children exposed to carbamazepine and phenytoin.

The findings of both physical and cognitive problems with prenatal exposure show that the drug probably is not safe for use at any time during pregnancy, said Dr. Michael Privitera, director of the Cincinnati Epilepsy Center and another of the NEAD investigators.

“The neural tube defects [with which valproate is associated] occur during the first trimester, so there has been a question whether we might be able to use valproate later in pregnancy. This study shows that the answer is no, because cognitive development in the fetus occurs during the third trimester,” Dr. Privitera said in an interview.

Children exposed to valproate in utero have significantly lower IQs at age 3 than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator on the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor of neurology, Emory University, Atlanta, and his associates reported a planned 3-year interim analysis (N. Engl. J. Med. 2009;360:1597–605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most children (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate.

IQ scores were adjusted for factors that could significantly affect cognitive development, some of which were maternal IQ, age at delivery, education, type of epilepsy, and seizure frequency.

Children exposed to valproate had the lowest mean IQs of any of the exposure groups (92)—significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99. These did not vary significantly from one another.

The association of valproate with reduced IQ held after adjustment for confounders in both a linear regression and subgroup analysis, the investigators said.

They also examined whether the IQ scores were related to AED dosage. In this analysis, only valproate maintained a significant dose-response relationship. Additionally, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said. A Finnish study reported a mean reduction of 13 points in verbal IQ in valproate-exposed children, compared with controls. A British study found that valproate exposure increased developmental delays, increased special education needs, and reduced verbal IQ, compared with unexposed children and children exposed to carbamazepine and phenytoin.

The findings of both physical and cognitive problems with prenatal exposure show that the drug probably is not safe for use at any time during pregnancy, said Dr. Michael Privitera, director of the Cincinnati Epilepsy Center and another of the NEAD investigators.

“The neural tube defects [with which valproate is associated] occur during the first trimester, so there has been a question whether we might be able to use valproate later in pregnancy. This study shows that the answer is no, because cognitive development in the fetus occurs during the third trimester,” Dr. Privitera said in an interview.

Children exposed to valproate in utero have significantly lower IQs at age 3 than do children exposed to other antiepileptics during gestation, according to findings from the interim analysis of a large international study.

The drug previously had been associated with a higher rate of birth defects in children exposed prenatally. The combination of findings strengthens a recommendation to avoid valproate as a first-line antiepileptic in women who may bear children, Dr. Kimford J. Meador said in an interview.

“Valproate poses a special risk for both congenital malformations and for cognitive impairment,” said Dr. Meador, principal investigator on the Neurodevelopmental Effects of Antiepileptics Drugs (NEAD) study. “Since there are other therapeutic options, it would seem prudent to try those first. At a minimum, it is critical that physicians inform women of this risk when prescribing valproate so that they may make an informed choice.”

NEAD is an ongoing study of 309 children, including three sets of twins, born in either the United States or the United Kingdom from 1999 to 2004, whose mothers were taking a single antiepileptic drug (AED): carbamazepine, lamotrigine, phenytoin, or valproate. The children are being followed to age 6. Dr. Meador, professor of neurology, Emory University, Atlanta, and his associates reported a planned 3-year interim analysis (N. Engl. J. Med. 2009;360:1597–605).

All of the 303 women in the study were taking the drugs for a seizure disorder. Their mean age at delivery was 30 years. Most women were well controlled on their AED, with about 80% having no seizures during their pregnancy.

Most children (258) underwent cognitive assessment at either 2 or 3 years of age, or at both ages. Of these, 73 (28%) had been exposed to carbamazepine, 84 (32%) to lamotrigine, 48 (19%) to phenytoin, and 53 (21%) to valproate.

IQ scores were adjusted for factors that could significantly affect cognitive development, some of which were maternal IQ, age at delivery, education, type of epilepsy, and seizure frequency.

Children exposed to valproate had the lowest mean IQs of any of the exposure groups (92)—significantly lower than those of any other treatment group. The mean IQ in those exposed to carbamazepine was 98; to lamotrigine, 101; and to phenytoin, 99. These did not vary significantly from one another.

The association of valproate with reduced IQ held after adjustment for confounders in both a linear regression and subgroup analysis, the investigators said.

They also examined whether the IQ scores were related to AED dosage. In this analysis, only valproate maintained a significant dose-response relationship. Additionally, higher maternal IQs were associated with higher child IQs in all of the treatment groups except valproate.

The results are consistent with several European studies that have found poor cognitive outcomes in children exposed to the drug prenatally, the investigators said. A Finnish study reported a mean reduction of 13 points in verbal IQ in valproate-exposed children, compared with controls. A British study found that valproate exposure increased developmental delays, increased special education needs, and reduced verbal IQ, compared with unexposed children and children exposed to carbamazepine and phenytoin.

The findings of both physical and cognitive problems with prenatal exposure show that the drug probably is not safe for use at any time during pregnancy, said Dr. Michael Privitera, director of the Cincinnati Epilepsy Center and another of the NEAD investigators.

“The neural tube defects [with which valproate is associated] occur during the first trimester, so there has been a question whether we might be able to use valproate later in pregnancy. This study shows that the answer is no, because cognitive development in the fetus occurs during the third trimester,” Dr. Privitera said in an interview.

WASHINGTON — If you're not already taking a serious look at the bone health of patients with celiac disease, you should be, according to Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York.

The gastrointestinal disease presents a double-edged sword: Patients with celiac disease have an increased risk of osteoporosis and fragility fractures, not only because their intestines poorly absorb calcium and vitamin D, but also because the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Study results 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.

The role of autoimmune inflammation on the bone health of these patients is not as widely appreciated as is the issue of vitamin D and calcium malabsorption, Dr. Green said at an international symposium sponsored by the National Osteoporosis Foundation.

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.

Several 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.

“After 16 months on a gluten-free diet, bone mineral density increased by more than 7% at the femoral neck in celiac patients who also had osteoporosis,” Dr. Green said (Am. J. Gastroenterol. 2001;96:112–9).

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, although the exact mechanism by which this occurs is unknown, he said. Several studies show improvements in bone density as cytokine levels diminish on a gluten-free diet (Am. J. Gastroenterol. 1998;93:413–8; Scand. J. Gastroenterol. 1999;34:904–8).

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.

Whatever the mechanism, the bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, Dr. Green said.

A 2008 meta-analysis of seven studies showed that patients were up to 10 times more likely than were controls to suffer a fragility fracture (Dig. Liver Dis. 2008;40:46–53).

Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, Dr. Green said. Calcium and vitamin D supplements are important, but no studies have shown whether these patients need larger doses than those of the general population.

Bisphosphonates should be used with caution, he added, as there have been several case reports of bisphosphonate-induced hypocalcemia in this patient group.

On a gluten-free diet, bone mineral density increased by more than 7% at the femoral neck in celiac patients. DR. GREEN

WASHINGTON — If you're not already taking a serious look at the bone health of patients with celiac disease, you should be, according to Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York.

The gastrointestinal disease presents a double-edged sword: Patients with celiac disease have an increased risk of osteoporosis and fragility fractures, not only because their intestines poorly absorb calcium and vitamin D, but also because the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Study results 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.

The role of autoimmune inflammation on the bone health of these patients is not as widely appreciated as is the issue of vitamin D and calcium malabsorption, Dr. Green said at an international symposium sponsored by the National Osteoporosis Foundation.

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.

Several 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.

“After 16 months on a gluten-free diet, bone mineral density increased by more than 7% at the femoral neck in celiac patients who also had osteoporosis,” Dr. Green said (Am. J. Gastroenterol. 2001;96:112–9).

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, although the exact mechanism by which this occurs is unknown, he said. Several studies show improvements in bone density as cytokine levels diminish on a gluten-free diet (Am. J. Gastroenterol. 1998;93:413–8; Scand. J. Gastroenterol. 1999;34:904–8).

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.

Whatever the mechanism, the bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, Dr. Green said.

A 2008 meta-analysis of seven studies showed that patients were up to 10 times more likely than were controls to suffer a fragility fracture (Dig. Liver Dis. 2008;40:46–53).

Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, Dr. Green said. Calcium and vitamin D supplements are important, but no studies have shown whether these patients need larger doses than those of the general population.

Bisphosphonates should be used with caution, he added, as there have been several case reports of bisphosphonate-induced hypocalcemia in this patient group.

On a gluten-free diet, bone mineral density increased by more than 7% at the femoral neck in celiac patients. DR. GREEN

WASHINGTON — If you're not already taking a serious look at the bone health of patients with celiac disease, you should be, according to Dr. Peter Green, director of the Celiac Disease Center at Columbia University, New York.

The gastrointestinal disease presents a double-edged sword: Patients with celiac disease have an increased risk of osteoporosis and fragility fractures, not only because their intestines poorly absorb calcium and vitamin D, but also because the disorder induces bone-destructive inflammatory and autoimmune responses, he said.

Study results 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.

The role of autoimmune inflammation on the bone health of these patients is not as widely appreciated as is the issue of vitamin D and calcium malabsorption, Dr. Green said at an international symposium sponsored by the National Osteoporosis Foundation.

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.

Several 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.

“After 16 months on a gluten-free diet, bone mineral density increased by more than 7% at the femoral neck in celiac patients who also had osteoporosis,” Dr. Green said (Am. J. Gastroenterol. 2001;96:112–9).

Proinflammatory circulating cytokines also are increased in celiac disease, and may contribute to decreases in bone density, although the exact mechanism by which this occurs is unknown, he said. Several studies show improvements in bone density as cytokine levels diminish on a gluten-free diet (Am. J. Gastroenterol. 1998;93:413–8; Scand. J. Gastroenterol. 1999;34:904–8).

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.

Whatever the mechanism, the bone loss associated with celiac disease results in a significantly increased risk of both peripheral and central fracture, Dr. Green said.

A 2008 meta-analysis of seven studies showed that patients were up to 10 times more likely than were controls to suffer a fragility fracture (Dig. Liver Dis. 2008;40:46–53).

Strict adherence to a gluten-free diet seems to be the best way to boost bone health in these patients, Dr. Green said. Calcium and vitamin D supplements are important, but no studies have shown whether these patients need larger doses than those of the general population.

Bisphosphonates should be used with caution, he added, as there have been several case reports of bisphosphonate-induced hypocalcemia in this patient group.

On a gluten-free diet, bone mineral density increased by more than 7% at the femoral neck in celiac patients. DR. GREEN

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; two of the subjects progressed from osteopenia to osteoporosis, 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.

She and her colleagues performed a chart review of 104 women who were taking the drugs for breast cancer and were evaluated for bone health. Of these, 61 (58%) had osteopenia. The patients' mean age was 58 years; they had been on aromatase inhibitor therapy for up to 2 years. Eighteen percent (11 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. The progression in bone loss occurred despite increased compliance with vitamin D supplements. At baseline, 74% were taking at least 1,000 mg/day of vitamin D, although 41% were still deficient. At the end of the follow-up period, vitamin D intake had significantly increased, with only 25% still deficient, Dr. Taxel noted.

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; two of the subjects progressed from osteopenia to osteoporosis, 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.

She and her colleagues performed a chart review of 104 women who were taking the drugs for breast cancer and were evaluated for bone health. Of these, 61 (58%) had osteopenia. The patients' mean age was 58 years; they had been on aromatase inhibitor therapy for up to 2 years. Eighteen percent (11 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. The progression in bone loss occurred despite increased compliance with vitamin D supplements. At baseline, 74% were taking at least 1,000 mg/day of vitamin D, although 41% were still deficient. At the end of the follow-up period, vitamin D intake had significantly increased, with only 25% still deficient, Dr. Taxel noted.

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; two of the subjects progressed from osteopenia to osteoporosis, 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.

She and her colleagues performed a chart review of 104 women who were taking the drugs for breast cancer and were evaluated for bone health. Of these, 61 (58%) had osteopenia. The patients' mean age was 58 years; they had been on aromatase inhibitor therapy for up to 2 years. Eighteen percent (11 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. The progression in bone loss occurred despite increased compliance with vitamin D supplements. At baseline, 74% were taking at least 1,000 mg/day of vitamin D, although 41% were still deficient. At the end of the follow-up period, vitamin D intake had significantly increased, with only 25% still deficient, Dr. Taxel noted.

WASHINGTON — Three-fourths of patients hospitalized for a hip fracture do not receive an osteoporosis diagnosis before discharge, and the majority are not taking a bisphosphonate at discharge or 6 months after the injury, a study has shown.

The findings are dismaying, said Dr. Pardeep Bansal, because 24% of patients older than 50 years who sustain an osteoporotic hip fracture die within a year. “The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack,” said Dr. Bansal, chief resident at the Scranton-Temple Residency Program, Scranton, Pa. “But if you have a heart attack, no physician is going to let you leave the hospital without aspirin, a beta-blocker, and a statin. If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis, much less the appropriate treatment.”

The two-part study began with a chart review of 191 patients who were admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At the time of discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium; patients who had been diagnosed with osteoporosis were significantly more likely to be taking both calcium and vitamin D than were patients without a diagnosis.

Furthermore, only 15% were taking a bisphosphonate at discharge, Dr Bansal said. Clinical contraindications did not appear to play a significant role in the lack of treatment: Only 2% of patients had a glomerular filtration rate of less than 30 mL/min per 1.73 m

Dr. Bansal then performed a telephone survey of the 105 patients who could be contacted; 33% of the original cohort had died since their fractures, and another 12% could not be found. All of the patients interviewed reported having seen their primary care physicians within 6 months of the fracture. Yet still, only 50% had received a diagnosis of osteoporosis, 50% were taking calcium, 40% were taking vitamin D, and only 28% were taking a bisphosphonate. “Another painful finding was that 14% of the group had experienced a subsequent fragility fracture.”

To help improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues have instituted a standardized protocol. “It's very simple,” he said. “Any patient who comes in with a fracture suggestive of osteoporosis is started on calcium, vitamin D, and a bisphosphonate before discharge. If they have a contraindication to a bisphosphonate, such as an allergy or a low GFR, then we call the family physician and discuss an alternative treatment.”

Treatment should not be delayed until a scan can be obtained, said Dr. Bansal, who presented the study at an international symposium sponsored by the National Osteoporosis Foundation. He had no conflicts of interest to declare.

'The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack.' DR. BANSAL

WASHINGTON — Three-fourths of patients hospitalized for a hip fracture do not receive an osteoporosis diagnosis before discharge, and the majority are not taking a bisphosphonate at discharge or 6 months after the injury, a study has shown.

The findings are dismaying, said Dr. Pardeep Bansal, because 24% of patients older than 50 years who sustain an osteoporotic hip fracture die within a year. “The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack,” said Dr. Bansal, chief resident at the Scranton-Temple Residency Program, Scranton, Pa. “But if you have a heart attack, no physician is going to let you leave the hospital without aspirin, a beta-blocker, and a statin. If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis, much less the appropriate treatment.”

The two-part study began with a chart review of 191 patients who were admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At the time of discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium; patients who had been diagnosed with osteoporosis were significantly more likely to be taking both calcium and vitamin D than were patients without a diagnosis.

Furthermore, only 15% were taking a bisphosphonate at discharge, Dr Bansal said. Clinical contraindications did not appear to play a significant role in the lack of treatment: Only 2% of patients had a glomerular filtration rate of less than 30 mL/min per 1.73 m

Dr. Bansal then performed a telephone survey of the 105 patients who could be contacted; 33% of the original cohort had died since their fractures, and another 12% could not be found. All of the patients interviewed reported having seen their primary care physicians within 6 months of the fracture. Yet still, only 50% had received a diagnosis of osteoporosis, 50% were taking calcium, 40% were taking vitamin D, and only 28% were taking a bisphosphonate. “Another painful finding was that 14% of the group had experienced a subsequent fragility fracture.”

To help improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues have instituted a standardized protocol. “It's very simple,” he said. “Any patient who comes in with a fracture suggestive of osteoporosis is started on calcium, vitamin D, and a bisphosphonate before discharge. If they have a contraindication to a bisphosphonate, such as an allergy or a low GFR, then we call the family physician and discuss an alternative treatment.”

Treatment should not be delayed until a scan can be obtained, said Dr. Bansal, who presented the study at an international symposium sponsored by the National Osteoporosis Foundation. He had no conflicts of interest to declare.

'The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack.' DR. BANSAL

WASHINGTON — Three-fourths of patients hospitalized for a hip fracture do not receive an osteoporosis diagnosis before discharge, and the majority are not taking a bisphosphonate at discharge or 6 months after the injury, a study has shown.

The findings are dismaying, said Dr. Pardeep Bansal, because 24% of patients older than 50 years who sustain an osteoporotic hip fracture die within a year. “The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack,” said Dr. Bansal, chief resident at the Scranton-Temple Residency Program, Scranton, Pa. “But if you have a heart attack, no physician is going to let you leave the hospital without aspirin, a beta-blocker, and a statin. If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis, much less the appropriate treatment.”

The two-part study began with a chart review of 191 patients who were admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At the time of discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium; patients who had been diagnosed with osteoporosis were significantly more likely to be taking both calcium and vitamin D than were patients without a diagnosis.

Furthermore, only 15% were taking a bisphosphonate at discharge, Dr Bansal said. Clinical contraindications did not appear to play a significant role in the lack of treatment: Only 2% of patients had a glomerular filtration rate of less than 30 mL/min per 1.73 m

Dr. Bansal then performed a telephone survey of the 105 patients who could be contacted; 33% of the original cohort had died since their fractures, and another 12% could not be found. All of the patients interviewed reported having seen their primary care physicians within 6 months of the fracture. Yet still, only 50% had received a diagnosis of osteoporosis, 50% were taking calcium, 40% were taking vitamin D, and only 28% were taking a bisphosphonate. “Another painful finding was that 14% of the group had experienced a subsequent fragility fracture.”

To help improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues have instituted a standardized protocol. “It's very simple,” he said. “Any patient who comes in with a fracture suggestive of osteoporosis is started on calcium, vitamin D, and a bisphosphonate before discharge. If they have a contraindication to a bisphosphonate, such as an allergy or a low GFR, then we call the family physician and discuss an alternative treatment.”

Treatment should not be delayed until a scan can be obtained, said Dr. Bansal, who presented the study at an international symposium sponsored by the National Osteoporosis Foundation. He had no conflicts of interest to declare.

'The 1-year mortality rate is higher than it is in some cancers, and even higher than it is after a heart attack.' DR. BANSAL