Michele G. Sullivan

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. At baseline, 18% (11 patients) were taking a bisphosphonate. 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 patient compliance with vitamin D supplements. At baseline, 74% of the women 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% of the women 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. At baseline, 18% (11 patients) were taking a bisphosphonate. 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 patient compliance with vitamin D supplements. At baseline, 74% of the women 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% of the women 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. At baseline, 18% (11 patients) were taking a bisphosphonate. 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 patient compliance with vitamin D supplements. At baseline, 74% of the women 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% of the women still deficient, Dr. Taxel noted.

Kinase inhibitors and antiangiogenic drugs may offer the first real hope of treating differentiated metastatic thyroid cancer, and seem to be especially effective in tumors exhibiting the B-type Raf kinase mutation.

Although such tumors are uncommon, there are no effective therapies for patients who develop them, Dr. Steven I. Sherman said at a thyroid cancer meeting sponsored by the American Thyroid Association.

“The standard treatment for thyroid cancer—radioactive iodine—is only effective as long as the cancer retains its ability to absorb and retain iodine,” said Dr. Sherman, medical director of the Endocrine Center at the M.D. Anderson Cancer Center, Houston. “At least half the time these metastatic tumors have lost that ability, and radioactive iodine won't work.”

For patients who have slow-growing, asymptomatic metastatic thyroid tumors, the adverse effects of treatment might be worse than the disease itself, Dr. Sherman said in an interview. “But for those whose cancer is progressing, affecting lung function, or causing bone problems, there is really no good option.”

The low incidence of these tumors has stymied many clinical trials: From 1975 to 1999, 15 trials were initiated and only 5 ended with published results, Dr. Sherman said.

However, recent discoveries of mutations that cause aggressive thyroid tumors have inspired new hope. The B-type Raf kinase (BRAF) mutation is the most important, accounting for about 40% of papillary thyroid cancers. “In papillary thyroid cancer, the BRAF tumors are more likely to be aggressive, to recur, and to be radioiodine resistant,” he said. BRAF mutations also occur in several other solid tumors, a fact that has added weight to this body of research.

The BRAF mutation interferes with tumor-suppressor genes and silences genes that metabolize iodine. It also increases the production of vascular endothelial growth factor (VEGF), making these tumors a potential target for antiangiogenics—drugs that shut off rampant tumor-feeding vascular growth.

Two small phase I trials of BRAF inhibitors have raised cautious enthusiasm, Dr. Sherman said.

Exelixis Inc. has released results of a trial of its compound, XL281, in 29 patients, 5 of whom had papillary thyroid cancer. The five patients with papillary thyroid cancer, two with a confirmed BRAF mutation, have had stable disease for up to 68 weeks, according to the company Web site.

PLX4032 is another BRAF inhibitor in phase I clinical trial, this one in joint development by Plexxikon Inc. and Roche.

“In these studies we are seeing stabilized disease, although not an overwhelmingly dramatic response, by inhibiting BRAF,” Dr. Sherman said.

A second group of trials has examined the effect of directly inhibiting VEGF receptors. Last year, Dr. Sherman published the results of a phase II trial of motesanib in differentiated thyroid cancer. The open-label trial comprised 93 patients with progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer. Stable disease occurred in 67% of the patients, and was maintained for 24 weeks or longer in 35% (N. Engl. J. Med. 2008;359:31–42).

BRAF-mutation tumors were particularly sensitive to motesanib. “The ability to stop the tumor's growth was twice as high in BRAF tumors,” Dr. Sherman said.

Two other 2008 trials examined the effects of sorafenib and axitinib in advanced thyroid cancers, with similar results, he said. “The thing all three trials have in common is the inhibition of the VEGF receptor. From these studies, we think there is strong evidence that antiangiogenic drugs offer a useful treatment for patients with metastatic differentiated thyroid cancer.”

The American Thyroid Association now recommends that patients with these tumors who are not enrolled in clinical trials be treated with one of the approved kinase inhibitors, preferably sorafenib.

Dr. Sherman said he has received research grants, honoraria, and speaking and consulting fees from numerous companies involved in cancer drug development, including Exelixis Inc., Amgen Inc., Bayer, and Plexxikon.

Kinase inhibitors and antiangiogenic drugs may offer the first real hope of treating differentiated metastatic thyroid cancer, and seem to be especially effective in tumors exhibiting the B-type Raf kinase mutation.

Although such tumors are uncommon, there are no effective therapies for patients who develop them, Dr. Steven I. Sherman said at a thyroid cancer meeting sponsored by the American Thyroid Association.

“The standard treatment for thyroid cancer—radioactive iodine—is only effective as long as the cancer retains its ability to absorb and retain iodine,” said Dr. Sherman, medical director of the Endocrine Center at the M.D. Anderson Cancer Center, Houston. “At least half the time these metastatic tumors have lost that ability, and radioactive iodine won't work.”

For patients who have slow-growing, asymptomatic metastatic thyroid tumors, the adverse effects of treatment might be worse than the disease itself, Dr. Sherman said in an interview. “But for those whose cancer is progressing, affecting lung function, or causing bone problems, there is really no good option.”

The low incidence of these tumors has stymied many clinical trials: From 1975 to 1999, 15 trials were initiated and only 5 ended with published results, Dr. Sherman said.

However, recent discoveries of mutations that cause aggressive thyroid tumors have inspired new hope. The B-type Raf kinase (BRAF) mutation is the most important, accounting for about 40% of papillary thyroid cancers. “In papillary thyroid cancer, the BRAF tumors are more likely to be aggressive, to recur, and to be radioiodine resistant,” he said. BRAF mutations also occur in several other solid tumors, a fact that has added weight to this body of research.

The BRAF mutation interferes with tumor-suppressor genes and silences genes that metabolize iodine. It also increases the production of vascular endothelial growth factor (VEGF), making these tumors a potential target for antiangiogenics—drugs that shut off rampant tumor-feeding vascular growth.

Two small phase I trials of BRAF inhibitors have raised cautious enthusiasm, Dr. Sherman said.

Exelixis Inc. has released results of a trial of its compound, XL281, in 29 patients, 5 of whom had papillary thyroid cancer. The five patients with papillary thyroid cancer, two with a confirmed BRAF mutation, have had stable disease for up to 68 weeks, according to the company Web site.

PLX4032 is another BRAF inhibitor in phase I clinical trial, this one in joint development by Plexxikon Inc. and Roche.

“In these studies we are seeing stabilized disease, although not an overwhelmingly dramatic response, by inhibiting BRAF,” Dr. Sherman said.

A second group of trials has examined the effect of directly inhibiting VEGF receptors. Last year, Dr. Sherman published the results of a phase II trial of motesanib in differentiated thyroid cancer. The open-label trial comprised 93 patients with progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer. Stable disease occurred in 67% of the patients, and was maintained for 24 weeks or longer in 35% (N. Engl. J. Med. 2008;359:31–42).

BRAF-mutation tumors were particularly sensitive to motesanib. “The ability to stop the tumor's growth was twice as high in BRAF tumors,” Dr. Sherman said.

Two other 2008 trials examined the effects of sorafenib and axitinib in advanced thyroid cancers, with similar results, he said. “The thing all three trials have in common is the inhibition of the VEGF receptor. From these studies, we think there is strong evidence that antiangiogenic drugs offer a useful treatment for patients with metastatic differentiated thyroid cancer.”

The American Thyroid Association now recommends that patients with these tumors who are not enrolled in clinical trials be treated with one of the approved kinase inhibitors, preferably sorafenib.

Dr. Sherman said he has received research grants, honoraria, and speaking and consulting fees from numerous companies involved in cancer drug development, including Exelixis Inc., Amgen Inc., Bayer, and Plexxikon.

Kinase inhibitors and antiangiogenic drugs may offer the first real hope of treating differentiated metastatic thyroid cancer, and seem to be especially effective in tumors exhibiting the B-type Raf kinase mutation.

Although such tumors are uncommon, there are no effective therapies for patients who develop them, Dr. Steven I. Sherman said at a thyroid cancer meeting sponsored by the American Thyroid Association.

“The standard treatment for thyroid cancer—radioactive iodine—is only effective as long as the cancer retains its ability to absorb and retain iodine,” said Dr. Sherman, medical director of the Endocrine Center at the M.D. Anderson Cancer Center, Houston. “At least half the time these metastatic tumors have lost that ability, and radioactive iodine won't work.”

For patients who have slow-growing, asymptomatic metastatic thyroid tumors, the adverse effects of treatment might be worse than the disease itself, Dr. Sherman said in an interview. “But for those whose cancer is progressing, affecting lung function, or causing bone problems, there is really no good option.”

The low incidence of these tumors has stymied many clinical trials: From 1975 to 1999, 15 trials were initiated and only 5 ended with published results, Dr. Sherman said.

However, recent discoveries of mutations that cause aggressive thyroid tumors have inspired new hope. The B-type Raf kinase (BRAF) mutation is the most important, accounting for about 40% of papillary thyroid cancers. “In papillary thyroid cancer, the BRAF tumors are more likely to be aggressive, to recur, and to be radioiodine resistant,” he said. BRAF mutations also occur in several other solid tumors, a fact that has added weight to this body of research.

The BRAF mutation interferes with tumor-suppressor genes and silences genes that metabolize iodine. It also increases the production of vascular endothelial growth factor (VEGF), making these tumors a potential target for antiangiogenics—drugs that shut off rampant tumor-feeding vascular growth.

Two small phase I trials of BRAF inhibitors have raised cautious enthusiasm, Dr. Sherman said.

Exelixis Inc. has released results of a trial of its compound, XL281, in 29 patients, 5 of whom had papillary thyroid cancer. The five patients with papillary thyroid cancer, two with a confirmed BRAF mutation, have had stable disease for up to 68 weeks, according to the company Web site.

PLX4032 is another BRAF inhibitor in phase I clinical trial, this one in joint development by Plexxikon Inc. and Roche.

“In these studies we are seeing stabilized disease, although not an overwhelmingly dramatic response, by inhibiting BRAF,” Dr. Sherman said.

A second group of trials has examined the effect of directly inhibiting VEGF receptors. Last year, Dr. Sherman published the results of a phase II trial of motesanib in differentiated thyroid cancer. The open-label trial comprised 93 patients with progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer. Stable disease occurred in 67% of the patients, and was maintained for 24 weeks or longer in 35% (N. Engl. J. Med. 2008;359:31–42).

BRAF-mutation tumors were particularly sensitive to motesanib. “The ability to stop the tumor's growth was twice as high in BRAF tumors,” Dr. Sherman said.

Two other 2008 trials examined the effects of sorafenib and axitinib in advanced thyroid cancers, with similar results, he said. “The thing all three trials have in common is the inhibition of the VEGF receptor. From these studies, we think there is strong evidence that antiangiogenic drugs offer a useful treatment for patients with metastatic differentiated thyroid cancer.”

The American Thyroid Association now recommends that patients with these tumors who are not enrolled in clinical trials be treated with one of the approved kinase inhibitors, preferably sorafenib.

Dr. Sherman said he has received research grants, honoraria, and speaking and consulting fees from numerous companies involved in cancer drug development, including Exelixis Inc., Amgen Inc., Bayer, and Plexxikon.

Although generic versions of Topamax will soon be available, some neurologists are concerned the new formulations may endanger patients at high risk of seizure complications.

The Food and Drug Administration approved the marketing of generic topiramate for seizure disorders in April, and maintains that generic formulations of any drug must be bioequivalent to the brand formulation. But the agency's accepted bioequivalence range of 80%–125% could put some patients at risk for breakthrough seizures or increased side effects, Dr. Michael Privitera said.

“The FDA's bioequivalence requirements are not based on any strong evidence,” said Dr. Privitera, professor of neurology at the University of Cincinnati. “There are no studies that say people with epilepsy will do well within that range. The FDA could be correct in saying that generic formulations will fall within that range, but there is no way of knowing if that that range is good for our patients.”

Dr. Stuart Black, medical director of the Dallas Headache Association, agreed that the lack of evidence clouds the issue of which patients might experience problems if switched to a generic formulation. “We don't have any data at all on the similar comparison of using a generic antiepileptic for migraine as opposed to a nongeneric,” said Dr. Black, who is also the medical director of neurology and codirector of the Neuroscience Center at Baylor University Medical Center, Dallas.

The American Epilepsy Society recommends that generics should not be substituted for a brand formulation without physician and patient approval.

Although generic versions of Topamax will soon be available, some neurologists are concerned the new formulations may endanger patients at high risk of seizure complications.

The Food and Drug Administration approved the marketing of generic topiramate for seizure disorders in April, and maintains that generic formulations of any drug must be bioequivalent to the brand formulation. But the agency's accepted bioequivalence range of 80%–125% could put some patients at risk for breakthrough seizures or increased side effects, Dr. Michael Privitera said.

“The FDA's bioequivalence requirements are not based on any strong evidence,” said Dr. Privitera, professor of neurology at the University of Cincinnati. “There are no studies that say people with epilepsy will do well within that range. The FDA could be correct in saying that generic formulations will fall within that range, but there is no way of knowing if that that range is good for our patients.”

Dr. Stuart Black, medical director of the Dallas Headache Association, agreed that the lack of evidence clouds the issue of which patients might experience problems if switched to a generic formulation. “We don't have any data at all on the similar comparison of using a generic antiepileptic for migraine as opposed to a nongeneric,” said Dr. Black, who is also the medical director of neurology and codirector of the Neuroscience Center at Baylor University Medical Center, Dallas.

The American Epilepsy Society recommends that generics should not be substituted for a brand formulation without physician and patient approval.

Although generic versions of Topamax will soon be available, some neurologists are concerned the new formulations may endanger patients at high risk of seizure complications.

The Food and Drug Administration approved the marketing of generic topiramate for seizure disorders in April, and maintains that generic formulations of any drug must be bioequivalent to the brand formulation. But the agency's accepted bioequivalence range of 80%–125% could put some patients at risk for breakthrough seizures or increased side effects, Dr. Michael Privitera said.

“The FDA's bioequivalence requirements are not based on any strong evidence,” said Dr. Privitera, professor of neurology at the University of Cincinnati. “There are no studies that say people with epilepsy will do well within that range. The FDA could be correct in saying that generic formulations will fall within that range, but there is no way of knowing if that that range is good for our patients.”

Dr. Stuart Black, medical director of the Dallas Headache Association, agreed that the lack of evidence clouds the issue of which patients might experience problems if switched to a generic formulation. “We don't have any data at all on the similar comparison of using a generic antiepileptic for migraine as opposed to a nongeneric,” said Dr. Black, who is also the medical director of neurology and codirector of the Neuroscience Center at Baylor University Medical Center, Dallas.

The American Epilepsy Society recommends that generics should not be substituted for a brand formulation without physician and patient approval.

The days when the dietary supplements industry is allowed to regulate itself may be numbered following release of a federal report addressing growing concerns about the dietary supplement industry.

The report by the Government Accountability Office calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements.

Companies that manufacture the products are not required to identify themselves as such or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency can only ask for a voluntary recall, as it did in December when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements prior to marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Before then, they were regulated under the 1958 Food Additive Amendments to the Federal Food, Drug, and Cosmetic Act.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40–$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

One of the paper's key findings is that adverse events are probably significantly underreported, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

Dr. Altman noted that the medical literature contains virtually no data on which brand of supplements or herbal preparations most closely resemble their labeling. “You might think you are better off buying something that was made in the U.S., but in reality a lot of those are manufactured in China and then repackaged in the U.S.,” Dr. Altman said.

The unreliability of labeling “does present a real dilemma, because even if it's a safe product, like glucosamine, and you'd like to use it, there is no way of really knowing for certain what you're getting.”

Dr. David Riley, founder of the Integrative Medicine Institute in Santa Fe, N.M., said that “most of the products produced in the U.S. and Europe meet more stringent manufacturing requirements than those produced in China and India.”

Products imported from those countries have a history of poor quality. In fact, a recent study rather spectacularly showcased the problem, Dr. Riley said. Researchers obtained 190 Ayurvedic medicines from Internet sources and determined their components by x-ray fluorescence spectroscopy. They found that 20% contained some level of toxic metal (lead, mercury, or arsenic). U.S.-manufactured products were just as likely to be contaminated as were those made in India (22% vs. 19%).

But alternative medicine, like allopathic medicine, is based on a balance of risk and benefit, Dr. Riley pointed out. Still, herbal preparations are generally more benign than prescription medications. “I think it's important that people don't assume that 'natural' products are 100% safe, but the risks are still very low,” he said.

'There is no way of really knowing for certain what you're getting' when you buy a dietary supplement. DR. ALTMAN

The days when the dietary supplements industry is allowed to regulate itself may be numbered following release of a federal report addressing growing concerns about the dietary supplement industry.

The report by the Government Accountability Office calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements.

Companies that manufacture the products are not required to identify themselves as such or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency can only ask for a voluntary recall, as it did in December when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements prior to marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Before then, they were regulated under the 1958 Food Additive Amendments to the Federal Food, Drug, and Cosmetic Act.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40–$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

One of the paper's key findings is that adverse events are probably significantly underreported, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

Dr. Altman noted that the medical literature contains virtually no data on which brand of supplements or herbal preparations most closely resemble their labeling. “You might think you are better off buying something that was made in the U.S., but in reality a lot of those are manufactured in China and then repackaged in the U.S.,” Dr. Altman said.

The unreliability of labeling “does present a real dilemma, because even if it's a safe product, like glucosamine, and you'd like to use it, there is no way of really knowing for certain what you're getting.”

Dr. David Riley, founder of the Integrative Medicine Institute in Santa Fe, N.M., said that “most of the products produced in the U.S. and Europe meet more stringent manufacturing requirements than those produced in China and India.”

Products imported from those countries have a history of poor quality. In fact, a recent study rather spectacularly showcased the problem, Dr. Riley said. Researchers obtained 190 Ayurvedic medicines from Internet sources and determined their components by x-ray fluorescence spectroscopy. They found that 20% contained some level of toxic metal (lead, mercury, or arsenic). U.S.-manufactured products were just as likely to be contaminated as were those made in India (22% vs. 19%).

But alternative medicine, like allopathic medicine, is based on a balance of risk and benefit, Dr. Riley pointed out. Still, herbal preparations are generally more benign than prescription medications. “I think it's important that people don't assume that 'natural' products are 100% safe, but the risks are still very low,” he said.

'There is no way of really knowing for certain what you're getting' when you buy a dietary supplement. DR. ALTMAN

The days when the dietary supplements industry is allowed to regulate itself may be numbered following release of a federal report addressing growing concerns about the dietary supplement industry.

The report by the Government Accountability Office calls on the Food and Drug Administration to expand adverse event reporting and increase its efforts to educate the public about the safety, efficacy, and labeling of these products.

According to the 77-page report, the FDA should be tracking all levels of adverse events related to the use of dietary supplements and herbs, not just severe events. And, the report noted, despite the 2007 requirement for improved manufacturing practices, the FDA still lacks even the most basic ability to track the quality of dietary supplements.

Companies that manufacture the products are not required to identify themselves as such or to provide the FDA with information about the products, including the product name and ingredients, the report said. And if a product is found to be dangerous, the agency can only ask for a voluntary recall, as it did in December when Star Caps, a popular weight-loss supplement, was found to contain prescription-strength levels of the diuretic bumetanide.

The FDA lost its authority to regulate the ingredients of dietary supplements prior to marketing with the enactment of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Before then, they were regulated under the 1958 Food Additive Amendments to the Federal Food, Drug, and Cosmetic Act.

The issue of quality control has bothered Dr. Roy Altman for years. Supplements and herbal preparations designed to promote joint health and relieve pain are some of the most popular products on the market, grabbing almost as big a market share as weight-loss products, he said in an interview. “We are looking at probably $40–$60 billion spent on over-the-counter arthritis supplements each year,” he said, but noted that “this is only a fraction of what is spent on prescribed arthritis medications.”

Some of these products probably do have a beneficial effect in patients with rheumatic disorders, said Dr. Altman, professor of rheumatology at the University of California, Los Angeles. The problem is identifying which products actually contain what the label promises, and nothing else. “We, and a group of colleagues from Canada, once tested 10 different glucosamine products sold in the U.S. Four of them didn't even have glucosamine in them, and of the remaining six, four had much less than was stated on the product label.”

One of the paper's key findings is that adverse events are probably significantly underreported, said Lisa Shames, the GAO's director of Food Safety and Agriculture Issues. In December 2007, the FDA began requiring manufacturers of dietary supplements and herbal preparations to report all serious adverse events related to the use of their products. “Since then, FDA has had a threefold increase in the number of events reported, but the big question is whether this is all the events that are happening,” Ms. Shames said. From January through October 2008, the FDA received 948 reports of adverse events, compared with 298 over the same time frame in 2007. “FDA recently estimated that the true number of adverse events could be well over 50,000 each year. We recommended that the FDA require reporting of all adverse events, regardless of their severity.”

The agency should also increase its efforts to educate the public about the safety of supplements, the report concluded. “People think all these products are safe and approved by the FDA, and of course, this isn't the case,” Ms. Shames said.

Dr. Altman noted that the medical literature contains virtually no data on which brand of supplements or herbal preparations most closely resemble their labeling. “You might think you are better off buying something that was made in the U.S., but in reality a lot of those are manufactured in China and then repackaged in the U.S.,” Dr. Altman said.

The unreliability of labeling “does present a real dilemma, because even if it's a safe product, like glucosamine, and you'd like to use it, there is no way of really knowing for certain what you're getting.”

Dr. David Riley, founder of the Integrative Medicine Institute in Santa Fe, N.M., said that “most of the products produced in the U.S. and Europe meet more stringent manufacturing requirements than those produced in China and India.”

Products imported from those countries have a history of poor quality. In fact, a recent study rather spectacularly showcased the problem, Dr. Riley said. Researchers obtained 190 Ayurvedic medicines from Internet sources and determined their components by x-ray fluorescence spectroscopy. They found that 20% contained some level of toxic metal (lead, mercury, or arsenic). U.S.-manufactured products were just as likely to be contaminated as were those made in India (22% vs. 19%).

But alternative medicine, like allopathic medicine, is based on a balance of risk and benefit, Dr. Riley pointed out. Still, herbal preparations are generally more benign than prescription medications. “I think it's important that people don't assume that 'natural' products are 100% safe, but the risks are still very low,” he said.

'There is no way of really knowing for certain what you're getting' when you buy a dietary supplement. DR. ALTMAN

WASHINGTON — A single yearly infusion of zoledronic acid suppressed serum markers of bone turnover better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density in a randomized, placebo-controlled trial.

Although women who received the 5-mg infusion of zoledronic acid had significantly more immediate adverse events than did those receiving a placebo infusion, the long-term adverse event rate was similar in both groups, said Dr. Audrey Kriegman, who presented the data at a poster session during an international symposium sponsored by the National Osteoporosis Foundation.

The trial randomized 110 postmenopausal women (mean age, 60 years) to either the active infusion followed by 6 months of daily oral placebo, or to a placebo infusion followed by 6 months of daily raloxifene (60 mg). Most of the women (86%) were white; they were a mean of 13 years beyond menopause. About a third of the women (37%) had a mean T score of −2.5 or lower at the lumbar spine, total hip, or femoral neck; the remainder had a T score of −2.5 to −1.5.

The study's primary end points were the 6-month measurements of urine N-telopeptide of type I collagen corrected by creatinine (NTx) and bone-specific alkaline phosphatase (BSAP). Measurements of these markers at 2 and 4 months were the secondary end points.

The mean NTx:creatinine ratio was significantly lower in the zoledronic acid group than in the raloxifene group at all time points. (See box.) At 6 months, the decrease was 14% greater in the zoledronic acid group than in the raloxifene group.

The mean BSAP was also significantly lower at all time points in the zoledronic acid group. At 6 months, the BSAP level was 7% lower in the zoledronic acid group than in the raloxifene group.

The immediate adverse events were significantly higher in the zoledronic acid group, an expected finding, Dr. Kriegman said in an interview. “The overall incidence of adverse events was similar in the zoledronic acid and raloxifene treatment groups except during the first 3 days post infusion. This difference was mainly driven by transient postinfusion symptoms in the zoledronic acid treatment group. A mild pain reliever, such as acetaminophen, may reduce these symptoms.”

The immediate adverse events included nausea (36% zoledronic acid vs. 11% placebo), pyrexia (11% vs. 0%), myalgia (5% vs. 6%), pain (7% vs. 0%), chills (5% vs. 2%), and flulike illness (5% vs. 0%).

However, later-onset adverse events occurring more than 3 days after the infusion were “relatively balanced” between the groups, Dr. Kriegman said. These included sinusitis (7% each), urinary tract infection (7% vs. 4%), diarrhea (7% vs. 2%), constipation (2% vs. 6%), back pain (5% vs. 0%), and hypertension (5% vs. 0%).

Dr. Kriegman is the senior medical director for osteoporosis at Novartis Pharmaceuticals Corp. Novartis sponsored the study.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A single yearly infusion of zoledronic acid suppressed serum markers of bone turnover better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density in a randomized, placebo-controlled trial.

Although women who received the 5-mg infusion of zoledronic acid had significantly more immediate adverse events than did those receiving a placebo infusion, the long-term adverse event rate was similar in both groups, said Dr. Audrey Kriegman, who presented the data at a poster session during an international symposium sponsored by the National Osteoporosis Foundation.

The trial randomized 110 postmenopausal women (mean age, 60 years) to either the active infusion followed by 6 months of daily oral placebo, or to a placebo infusion followed by 6 months of daily raloxifene (60 mg). Most of the women (86%) were white; they were a mean of 13 years beyond menopause. About a third of the women (37%) had a mean T score of −2.5 or lower at the lumbar spine, total hip, or femoral neck; the remainder had a T score of −2.5 to −1.5.

The study's primary end points were the 6-month measurements of urine N-telopeptide of type I collagen corrected by creatinine (NTx) and bone-specific alkaline phosphatase (BSAP). Measurements of these markers at 2 and 4 months were the secondary end points.

The mean NTx:creatinine ratio was significantly lower in the zoledronic acid group than in the raloxifene group at all time points. (See box.) At 6 months, the decrease was 14% greater in the zoledronic acid group than in the raloxifene group.

The mean BSAP was also significantly lower at all time points in the zoledronic acid group. At 6 months, the BSAP level was 7% lower in the zoledronic acid group than in the raloxifene group.

The immediate adverse events were significantly higher in the zoledronic acid group, an expected finding, Dr. Kriegman said in an interview. “The overall incidence of adverse events was similar in the zoledronic acid and raloxifene treatment groups except during the first 3 days post infusion. This difference was mainly driven by transient postinfusion symptoms in the zoledronic acid treatment group. A mild pain reliever, such as acetaminophen, may reduce these symptoms.”

The immediate adverse events included nausea (36% zoledronic acid vs. 11% placebo), pyrexia (11% vs. 0%), myalgia (5% vs. 6%), pain (7% vs. 0%), chills (5% vs. 2%), and flulike illness (5% vs. 0%).

However, later-onset adverse events occurring more than 3 days after the infusion were “relatively balanced” between the groups, Dr. Kriegman said. These included sinusitis (7% each), urinary tract infection (7% vs. 4%), diarrhea (7% vs. 2%), constipation (2% vs. 6%), back pain (5% vs. 0%), and hypertension (5% vs. 0%).

Dr. Kriegman is the senior medical director for osteoporosis at Novartis Pharmaceuticals Corp. Novartis sponsored the study.

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A single yearly infusion of zoledronic acid suppressed serum markers of bone turnover better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density in a randomized, placebo-controlled trial.

Although women who received the 5-mg infusion of zoledronic acid had significantly more immediate adverse events than did those receiving a placebo infusion, the long-term adverse event rate was similar in both groups, said Dr. Audrey Kriegman, who presented the data at a poster session during an international symposium sponsored by the National Osteoporosis Foundation.

The trial randomized 110 postmenopausal women (mean age, 60 years) to either the active infusion followed by 6 months of daily oral placebo, or to a placebo infusion followed by 6 months of daily raloxifene (60 mg). Most of the women (86%) were white; they were a mean of 13 years beyond menopause. About a third of the women (37%) had a mean T score of −2.5 or lower at the lumbar spine, total hip, or femoral neck; the remainder had a T score of −2.5 to −1.5.

The study's primary end points were the 6-month measurements of urine N-telopeptide of type I collagen corrected by creatinine (NTx) and bone-specific alkaline phosphatase (BSAP). Measurements of these markers at 2 and 4 months were the secondary end points.

The mean NTx:creatinine ratio was significantly lower in the zoledronic acid group than in the raloxifene group at all time points. (See box.) At 6 months, the decrease was 14% greater in the zoledronic acid group than in the raloxifene group.

The mean BSAP was also significantly lower at all time points in the zoledronic acid group. At 6 months, the BSAP level was 7% lower in the zoledronic acid group than in the raloxifene group.

The immediate adverse events were significantly higher in the zoledronic acid group, an expected finding, Dr. Kriegman said in an interview. “The overall incidence of adverse events was similar in the zoledronic acid and raloxifene treatment groups except during the first 3 days post infusion. This difference was mainly driven by transient postinfusion symptoms in the zoledronic acid treatment group. A mild pain reliever, such as acetaminophen, may reduce these symptoms.”

The immediate adverse events included nausea (36% zoledronic acid vs. 11% placebo), pyrexia (11% vs. 0%), myalgia (5% vs. 6%), pain (7% vs. 0%), chills (5% vs. 2%), and flulike illness (5% vs. 0%).

However, later-onset adverse events occurring more than 3 days after the infusion were “relatively balanced” between the groups, Dr. Kriegman said. These included sinusitis (7% each), urinary tract infection (7% vs. 4%), diarrhea (7% vs. 2%), constipation (2% vs. 6%), back pain (5% vs. 0%), and hypertension (5% vs. 0%).

Dr. Kriegman is the senior medical director for osteoporosis at Novartis Pharmaceuticals Corp. Novartis sponsored the study.

ELSEVIER GLOBAL MEDICAL NEWS

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

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 admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium.

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

A telephone survey revealed that 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 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,” he said.

To improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues instituted a standardized protocol. “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.”

Although a dual-energy x-ray absorptiometry scan is a helpful diagnostic tool, Dr. Bansal said treatment should not be delayed until a scan can be obtained. “You have to wait for the fracture to heal and then schedule that as an outpatient, and during that time the patient can be lost to follow-up. … Don't delay the treatment while waiting for the scan.”

Dr. Bansal presented the study in a poster session at an international symposium sponsored by the National Osteoporosis Foundation. He had no conflicts of interest to declare.

'If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis.' DR. BANSAL

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

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 admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium.

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

A telephone survey revealed that 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 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,” he said.

To improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues instituted a standardized protocol. “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.”

Although a dual-energy x-ray absorptiometry scan is a helpful diagnostic tool, Dr. Bansal said treatment should not be delayed until a scan can be obtained. “You have to wait for the fracture to heal and then schedule that as an outpatient, and during that time the patient can be lost to follow-up. … Don't delay the treatment while waiting for the scan.”

Dr. Bansal presented the study in a poster session at an international symposium sponsored by the National Osteoporosis Foundation. He had no conflicts of interest to declare.

'If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis.' DR. BANSAL

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

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 admitted to a hospital with a hip fracture. Most (80%) were white females older than 70 years. At discharge, 25% had been assigned a diagnosis of osteoporosis. Only 30% were taking calcium.

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

A telephone survey revealed that 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 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,” he said.

To improve the rate of osteoporosis diagnosis at his hospital, Dr. Bansal and his colleagues instituted a standardized protocol. “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.”

Although a dual-energy x-ray absorptiometry scan is a helpful diagnostic tool, Dr. Bansal said treatment should not be delayed until a scan can be obtained. “You have to wait for the fracture to heal and then schedule that as an outpatient, and during that time the patient can be lost to follow-up. … Don't delay the treatment while waiting for the scan.”

Dr. Bansal presented the study in a poster session at an international symposium sponsored by the National Osteoporosis Foundation. He had no conflicts of interest to declare.

'If you have a hip fracture, you're likely to be discharged without even the underlying diagnosis.' DR. BANSAL

WASHINGTON — A single yearly infusion of zoledronic acid appears to prevent further bone loss in postmenopausal women with osteopenia and in women who have already had a hip fracture, two randomized controlled trials have concluded.

This is the first time the drug has been shown to be an effective preventive agent in treating osteopenic patients, said Dr. Chris Recknor, who presented the data in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture,” said Dr. Recknor, an internist specializing in the treatment of osteoporosis in Gainesville, Ga.

The 2-year Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention study cohort comprised 531 postmenopausal women with low bone mineral density (T scores of −1 to −2.5). They were randomized to one of three treatment regimens: two placebo infusions, given 12 months apart; two infusions of zoledronic acid 5 mg, given 12 months apart; or one infusion of 5 mg zoledronic acid, followed 12 months later by a placebo infusion.

The subjects' mean age was 60 years. Most (93%) were white. The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo. (See box.)

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

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

The study raises a tantalizing possibility, Dr. Recknor said in an interview. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

A subanalysis of a second HORIZON study has shown that zoledronic acid also benefits patients who have had a hip fracture—particularly the very elderly and those with the poorest bone quality.

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

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

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication. “These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore. “The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures.”

In a third study presented at the meeting, a single infusion of zoledronic acid was shown to suppress serum markers of bone turnover significantly better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density. (See story on p. 29.)

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

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A single yearly infusion of zoledronic acid appears to prevent further bone loss in postmenopausal women with osteopenia and in women who have already had a hip fracture, two randomized controlled trials have concluded.

This is the first time the drug has been shown to be an effective preventive agent in treating osteopenic patients, said Dr. Chris Recknor, who presented the data in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture,” said Dr. Recknor, an internist specializing in the treatment of osteoporosis in Gainesville, Ga.

The 2-year Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention study cohort comprised 531 postmenopausal women with low bone mineral density (T scores of −1 to −2.5). They were randomized to one of three treatment regimens: two placebo infusions, given 12 months apart; two infusions of zoledronic acid 5 mg, given 12 months apart; or one infusion of 5 mg zoledronic acid, followed 12 months later by a placebo infusion.

The subjects' mean age was 60 years. Most (93%) were white. The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo. (See box.)

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

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

The study raises a tantalizing possibility, Dr. Recknor said in an interview. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

A subanalysis of a second HORIZON study has shown that zoledronic acid also benefits patients who have had a hip fracture—particularly the very elderly and those with the poorest bone quality.

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

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

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication. “These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore. “The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures.”

In a third study presented at the meeting, a single infusion of zoledronic acid was shown to suppress serum markers of bone turnover significantly better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density. (See story on p. 29.)

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

ELSEVIER GLOBAL MEDICAL NEWS

WASHINGTON — A single yearly infusion of zoledronic acid appears to prevent further bone loss in postmenopausal women with osteopenia and in women who have already had a hip fracture, two randomized controlled trials have concluded.

This is the first time the drug has been shown to be an effective preventive agent in treating osteopenic patients, said Dr. Chris Recknor, who presented the data in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.

Using the drug prophylactically “allows clinicians a little more lead time in treating these patients, many of whom are at increased risk of a low-stress fracture,” said Dr. Recknor, an internist specializing in the treatment of osteoporosis in Gainesville, Ga.

The 2-year Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) prevention study cohort comprised 531 postmenopausal women with low bone mineral density (T scores of −1 to −2.5). They were randomized to one of three treatment regimens: two placebo infusions, given 12 months apart; two infusions of zoledronic acid 5 mg, given 12 months apart; or one infusion of 5 mg zoledronic acid, followed 12 months later by a placebo infusion.

The subjects' mean age was 60 years. Most (93%) were white. The study's main outcomes were 24-month changes in bone mineral density (BMD) at the lumbar spine, trochanter, femoral neck, distal radius, and total hip. The secondary end points were changes in markers of bone turnover. At 24 months (1 year after the second infusion), both active groups showed similar BMD increases at all sites that were significantly different from BMD changes with placebo. (See box.)

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

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

The study raises a tantalizing possibility, Dr. Recknor said in an interview. “You may be able to give this drug a couple of times to perimenopausal women and prevent the entire problem of bone loss.”

A subanalysis of a second HORIZON study has shown that zoledronic acid also benefits patients who have had a hip fracture—particularly the very elderly and those with the poorest bone quality.

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

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

Although Dr. Orwig said it's unclear why the oldest, least-dense bones benefited the most, the finding does carry a strongly positive clinical implication. “These patients who are at the highest risk are also the ones who are the least likely to be treated,” said Dr. Orwig of the department of epidemiology and preventive medicine at the University of Maryland Medical Center, Baltimore. “The thought may be that they have already had multiple fractures and there is probably not a lot more that can be done. But this study showed us that these individuals can benefit and that we can have a big short-term impact on their bone density and possibly even reduce the risk of more fractures.”

In a third study presented at the meeting, a single infusion of zoledronic acid was shown to suppress serum markers of bone turnover significantly better than 6 months of daily oral raloxifene in postmenopausal women with low bone mineral density. (See story on p. 29.)

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

ELSEVIER GLOBAL MEDICAL NEWS

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.

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

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

The role of autoimmune inflammation on bone health in these patients is not as widely appreciated as is the issue of vitamin D and calcium malabsorption, he 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, Dr. Green said.

“Tissue transglutaminase is a ubiquitous enzyme that is also present in bone,” he said. 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 explained.

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, as there have been several case reports of bisphosphonate-induced hypocalcemia in this group.

Celiac disease patients were up to 10 times more likely than were controls to suffer a fragility fracture. 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.

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

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

The role of autoimmune inflammation on bone health in these patients is not as widely appreciated as is the issue of vitamin D and calcium malabsorption, he 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, Dr. Green said.

“Tissue transglutaminase is a ubiquitous enzyme that is also present in bone,” he said. 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 explained.

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, as there have been several case reports of bisphosphonate-induced hypocalcemia in this group.

Celiac disease patients were up to 10 times more likely than were controls to suffer a fragility fracture. 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.

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

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

The role of autoimmune inflammation on bone health in these patients is not as widely appreciated as is the issue of vitamin D and calcium malabsorption, he 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, Dr. Green said.

“Tissue transglutaminase is a ubiquitous enzyme that is also present in bone,” he said. 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 explained.

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, as there have been several case reports of bisphosphonate-induced hypocalcemia in this group.

Celiac disease patients were up to 10 times more likely than were controls to suffer a fragility fracture. DR. GREEN

The United States recorded its highest-ever birth rate in 2007, with increases in births across every age and race group, according to preliminary data released by the National Center for Health Statistics.

More than 4.3 million babies were born in 2007, the report said, corresponding to a general fertility rate of 69.5 births per 1,000 women—the highest fertility level since 1990.

The 2007 birth rate surpassed the previous record holder, set during the post-World War II baby boom,” said Stephanie Ventura, chief of the center's department of reproductive statistics. “Previously, the country's highest-ever birth rate occurred in 1957, but of course, there are a lot more women of childbearing years in the United States now. The actual fertility rate of 2.1 children per woman [over a lifetime] is just about half of what it was in the baby boom years.”

Teens, unmarried women, and older women all had more babies in 2007 than they did in previous years, Ms. Ventura said in an interview.

“The teen birth rate went up for the second year in a row. We have had an overall increase of 5% since 2005,” although it's too soon to say if this trend represents a reversal of the 34% decline in births to teens aged 15–19 reported between 1991 and 2005.

Births to unmarried women made up 40% of the total births during 2007, Ms. Ventura said, a historic level. “This really is a trend and has been increasing since 2002 at a pretty good clip.” The year 2007 also boasted the highest number of births ever in this group (1.7 million), and the highest birth rate ever in this group (53/1,000 women).

The increase among unmarried women occurred in all age groups, not just among teenagers. “Unmarried mothers used to be synonymous with teen mothers, but not any more,” Ms. Ventura said. “Sixty percent of births to women in their early 20s were to unmarried mothers, as were almost one-third of births to women in their later 20s.” In fact, the largest increase in nonmarital births occurred among women aged 25–39 years. “I think the social stigma of being an unwed mother has pretty much disappeared,” she said. However, about 40% of these births were to women in cohabitation relationships.

About a third of births in the United States in 2007 were by C-section, said Joyce Martin, an epidemiologist with the center. “This is the 11th straight year that we have had an increase in the cesarean section rate,” she said in an interview. “Our data show an increase in the rate of primary C-sections and a decline in the rate of vaginal birth following C-section.”

The increase follows a trend of decreasing C-sections in the early to mid-1990s. Since 1996, the rate has risen 50%. The increase has been spread over all age and race groups, she added.

Preterm births declined 1% in 2007, to a rate of 13%. “Historically, we have seen small declines in the preterm rate followed by large increases, so it's too early to predict whether this heralds the beginning of a trend,” she commented. “We are certainly hopeful, particularly because we saw large, but not significant, declines in both preterm and low-birth weight babies.”

Another positive sign was that the declines in preterm and low-birth-weight babies were spread across the country, not driven by a few states. “The decline was also concentrated among late preterm births, a group that had risen quite dramatically in recent years. … Again, it's too soon to say what might be causing this change,” Dr. Martin said.

The full report is available at www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_12.pdf

The United States recorded its highest-ever birth rate in 2007, with increases in births across every age and race group, according to preliminary data released by the National Center for Health Statistics.

More than 4.3 million babies were born in 2007, the report said, corresponding to a general fertility rate of 69.5 births per 1,000 women—the highest fertility level since 1990.

The 2007 birth rate surpassed the previous record holder, set during the post-World War II baby boom,” said Stephanie Ventura, chief of the center's department of reproductive statistics. “Previously, the country's highest-ever birth rate occurred in 1957, but of course, there are a lot more women of childbearing years in the United States now. The actual fertility rate of 2.1 children per woman [over a lifetime] is just about half of what it was in the baby boom years.”

Teens, unmarried women, and older women all had more babies in 2007 than they did in previous years, Ms. Ventura said in an interview.

“The teen birth rate went up for the second year in a row. We have had an overall increase of 5% since 2005,” although it's too soon to say if this trend represents a reversal of the 34% decline in births to teens aged 15–19 reported between 1991 and 2005.

Births to unmarried women made up 40% of the total births during 2007, Ms. Ventura said, a historic level. “This really is a trend and has been increasing since 2002 at a pretty good clip.” The year 2007 also boasted the highest number of births ever in this group (1.7 million), and the highest birth rate ever in this group (53/1,000 women).

The increase among unmarried women occurred in all age groups, not just among teenagers. “Unmarried mothers used to be synonymous with teen mothers, but not any more,” Ms. Ventura said. “Sixty percent of births to women in their early 20s were to unmarried mothers, as were almost one-third of births to women in their later 20s.” In fact, the largest increase in nonmarital births occurred among women aged 25–39 years. “I think the social stigma of being an unwed mother has pretty much disappeared,” she said. However, about 40% of these births were to women in cohabitation relationships.

About a third of births in the United States in 2007 were by C-section, said Joyce Martin, an epidemiologist with the center. “This is the 11th straight year that we have had an increase in the cesarean section rate,” she said in an interview. “Our data show an increase in the rate of primary C-sections and a decline in the rate of vaginal birth following C-section.”

The increase follows a trend of decreasing C-sections in the early to mid-1990s. Since 1996, the rate has risen 50%. The increase has been spread over all age and race groups, she added.

Preterm births declined 1% in 2007, to a rate of 13%. “Historically, we have seen small declines in the preterm rate followed by large increases, so it's too early to predict whether this heralds the beginning of a trend,” she commented. “We are certainly hopeful, particularly because we saw large, but not significant, declines in both preterm and low-birth weight babies.”

Another positive sign was that the declines in preterm and low-birth-weight babies were spread across the country, not driven by a few states. “The decline was also concentrated among late preterm births, a group that had risen quite dramatically in recent years. … Again, it's too soon to say what might be causing this change,” Dr. Martin said.

The full report is available at www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_12.pdf

The United States recorded its highest-ever birth rate in 2007, with increases in births across every age and race group, according to preliminary data released by the National Center for Health Statistics.

More than 4.3 million babies were born in 2007, the report said, corresponding to a general fertility rate of 69.5 births per 1,000 women—the highest fertility level since 1990.

The 2007 birth rate surpassed the previous record holder, set during the post-World War II baby boom,” said Stephanie Ventura, chief of the center's department of reproductive statistics. “Previously, the country's highest-ever birth rate occurred in 1957, but of course, there are a lot more women of childbearing years in the United States now. The actual fertility rate of 2.1 children per woman [over a lifetime] is just about half of what it was in the baby boom years.”

Teens, unmarried women, and older women all had more babies in 2007 than they did in previous years, Ms. Ventura said in an interview.

“The teen birth rate went up for the second year in a row. We have had an overall increase of 5% since 2005,” although it's too soon to say if this trend represents a reversal of the 34% decline in births to teens aged 15–19 reported between 1991 and 2005.

Births to unmarried women made up 40% of the total births during 2007, Ms. Ventura said, a historic level. “This really is a trend and has been increasing since 2002 at a pretty good clip.” The year 2007 also boasted the highest number of births ever in this group (1.7 million), and the highest birth rate ever in this group (53/1,000 women).

The increase among unmarried women occurred in all age groups, not just among teenagers. “Unmarried mothers used to be synonymous with teen mothers, but not any more,” Ms. Ventura said. “Sixty percent of births to women in their early 20s were to unmarried mothers, as were almost one-third of births to women in their later 20s.” In fact, the largest increase in nonmarital births occurred among women aged 25–39 years. “I think the social stigma of being an unwed mother has pretty much disappeared,” she said. However, about 40% of these births were to women in cohabitation relationships.

About a third of births in the United States in 2007 were by C-section, said Joyce Martin, an epidemiologist with the center. “This is the 11th straight year that we have had an increase in the cesarean section rate,” she said in an interview. “Our data show an increase in the rate of primary C-sections and a decline in the rate of vaginal birth following C-section.”

The increase follows a trend of decreasing C-sections in the early to mid-1990s. Since 1996, the rate has risen 50%. The increase has been spread over all age and race groups, she added.

Preterm births declined 1% in 2007, to a rate of 13%. “Historically, we have seen small declines in the preterm rate followed by large increases, so it's too early to predict whether this heralds the beginning of a trend,” she commented. “We are certainly hopeful, particularly because we saw large, but not significant, declines in both preterm and low-birth weight babies.”

Another positive sign was that the declines in preterm and low-birth-weight babies were spread across the country, not driven by a few states. “The decline was also concentrated among late preterm births, a group that had risen quite dramatically in recent years. … Again, it's too soon to say what might be causing this change,” Dr. Martin said.

The full report is available at www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_12.pdf

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 with 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 > −2.5 and < −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%).

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, they wrote. In men, the weakening may be due to bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

BPV occurs when otoconia dislodge from the utricle and lodge in the semicircular canals. During head movement, the otoconia can stimulate the canals, which is interpreted as a sense of whirling dizziness and unbalance.

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 with 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 > −2.5 and < −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%).

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, they wrote. In men, the weakening may be due to bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

BPV occurs when otoconia dislodge from the utricle and lodge in the semicircular canals. During head movement, the otoconia can stimulate the canals, which is interpreted as a sense of whirling dizziness and unbalance.

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 with 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 > −2.5 and < −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%).

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, they wrote. In men, the weakening may be due to bone loss initiated by a combination of hormone deficiency, poor nutrition, and decreased physical activity.

BPV occurs when otoconia dislodge from the utricle and lodge in the semicircular canals. During head movement, the otoconia can stimulate the canals, which is interpreted as a sense of whirling dizziness and unbalance.