Osteoarthritis

SAN FRANCISCO — Recent data challenge the long-standing assumption that sufficient levels of calcium and vitamin D are fundamental in preventing and treating osteoporotic fracture, Eric S. Orwoll, M.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Calcium absorption and vitamin D levels decline with age. A number of studies over the years have solidified the idea that calcium and vitamin D supplements are effective and important in preventing osteoporosis and fractures, said Dr. Orwoll, professor of medicine at Oregon Health and Science University, Portland.

Findings from a large, well-designed study stirred up controversy when results indicated there were no differences in the rates of repeat fractures among patients with a previous fracture who took calcium, vitamin D, or calcium and vitamin D.

The investigators randomly assigned 5,292 patients aged 70 and older to one of four groups—800 IU daily oral vitamin D, 1,000 mg calcium, oral vitamin D combined with calcium, or placebo—and followed them for a median of 45 months (Lancet 2005;365:1621–8).

Among the total, 698 (13%) sustained a new low-trauma fracture. Of these, 183 (26%) were hip fractures. Investigators observed no significant differences in the incidence of new, low-trauma fractures between patients who received calcium vs. those who did not (12.6% vs. 13.7%); between those who received vitamin D₃ vs. those who did not (13.3% vs 13.1%) or between patients who received combination treatment and those who received placebo (12.6% vs. 13.4%).

Importantly, by 2 years into the Randomized Evaluation of Calcium or Vitamin D (RECORD) trial, only 55% of patients were still taking the calcium and vitamin D tablets, Dr. Orwoll noted. “This is more a compliance issue than an efficacy trial, but it's in the real world,” he said. Analysis of various subgroups could find no effects on fracture rates from the supplements.

The results contradict earlier findings. A 2003 study of 2,686 people aged 65–85 years who were vitamin D deficient found a 22% lower rate of fractures after 5 years in those who took oral vitamin D (100,000 IU every 4 months) vs. those who took placebo. A 2004 metaanalysis of five randomized, controlled trials of vitamin D for people older than 60 years found a 30% lower risk of falls in those taking vitamin D.

A 2005 metaanalysis of seven randomized trials of vitamin D supplementation with 9,820 participants showed that people taking higher doses (700–800 IU/day) of vitamin D had lower rates of hip fractures or any nonvertebral fractures than participants who took 400 IU/day. Nearly all studies included calcium supplements (JAMA 2005;293:2257–64).

Differences between the RECORD trial and earlier trials may account in part for the conflicting findings, Dr. Orwoll said. In an earlier trial in France, for example, 800 IU/day of vitamin D significantly reduced fracture risk, compared with placebo in frail, elderly patients with a mean age of 85 years; all resided in group housing and had very low baseline levels of calcium and vitamin D (Osteoporosis Int. 2002;13:257–64).

Patients in the RECORD trial were a bit younger (mean age 77 years), had somewhat higher baseline levels of calcium and vitamin D, and were home-dwelling instead of institutionalized. “So calcium and vitamin D might show the most robust effect in the frailest patients,” he suggested.

Whether or not calcium and vitamin D supplements reduce fracture risk, and in which patients, remains to be seen, but they are necessary for maintaining bone mass and muscle function, Dr. Orwoll said. Most adults don't get enough calcium and vitamin D, and current recommendations on adequate vitamin D levels are too low, he added.

The Institute of Medicine in 1997 recommended vitamin D doses of 200 IU/day for adults aged 31–50 years, 400 IU/day for ages 51–70, and 600 IU/ day for older people.

A serum level of 30–35 ng/mL of 25-hydroxyvitamin D (25[OH]D) may be ideal for maximizing GI absorption of calcium and avoiding elevated parathyroid levels, Dr. Orwoll noted. A recent poll of six experts suggested that much higher doses of vitamin D supplements are needed to reach those levels. The experts said that 1,000–1,600 IU/day vitamin D would be needed to reach serum levels of 30–32 ng/mL 25(OH)D.

Vitamin D and calcium supplements are inexpensive and safe, so there's little reason not to use them, he said. Recommended daily calcium requirements are scientifically reasonable, even though they're based more on physiologic data than on clinical outcome studies.

Institute of Medicine guidelines in 1997 recommended calcium doses of 1,000 mg/day for adults aged 25–50, 1,200 mg/day for older adults, and 1,000–1,300 mg/day for pregnant or lactating women.

Vitamin D supplementation should be at least 800–1,000 IU/day, Dr. Orwoll said. For pure nutritional inadequacy, it may be appropriate to treat with a loading dose of 50,000 IU per week for 2 months followed by 1,000 IU/day, depending on baseline vitamin D levels. Vitamin D deficiency due to malabsorption or increased catabolism may require doses as high as 100,000 IU/day, he said.

SAN FRANCISCO — Recent data challenge the long-standing assumption that sufficient levels of calcium and vitamin D are fundamental in preventing and treating osteoporotic fracture, Eric S. Orwoll, M.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Calcium absorption and vitamin D levels decline with age. A number of studies over the years have solidified the idea that calcium and vitamin D supplements are effective and important in preventing osteoporosis and fractures, said Dr. Orwoll, professor of medicine at Oregon Health and Science University, Portland.

Findings from a large, well-designed study stirred up controversy when results indicated there were no differences in the rates of repeat fractures among patients with a previous fracture who took calcium, vitamin D, or calcium and vitamin D.

The investigators randomly assigned 5,292 patients aged 70 and older to one of four groups—800 IU daily oral vitamin D, 1,000 mg calcium, oral vitamin D combined with calcium, or placebo—and followed them for a median of 45 months (Lancet 2005;365:1621–8).

Among the total, 698 (13%) sustained a new low-trauma fracture. Of these, 183 (26%) were hip fractures. Investigators observed no significant differences in the incidence of new, low-trauma fractures between patients who received calcium vs. those who did not (12.6% vs. 13.7%); between those who received vitamin D₃ vs. those who did not (13.3% vs 13.1%) or between patients who received combination treatment and those who received placebo (12.6% vs. 13.4%).

Importantly, by 2 years into the Randomized Evaluation of Calcium or Vitamin D (RECORD) trial, only 55% of patients were still taking the calcium and vitamin D tablets, Dr. Orwoll noted. “This is more a compliance issue than an efficacy trial, but it's in the real world,” he said. Analysis of various subgroups could find no effects on fracture rates from the supplements.

The results contradict earlier findings. A 2003 study of 2,686 people aged 65–85 years who were vitamin D deficient found a 22% lower rate of fractures after 5 years in those who took oral vitamin D (100,000 IU every 4 months) vs. those who took placebo. A 2004 metaanalysis of five randomized, controlled trials of vitamin D for people older than 60 years found a 30% lower risk of falls in those taking vitamin D.

A 2005 metaanalysis of seven randomized trials of vitamin D supplementation with 9,820 participants showed that people taking higher doses (700–800 IU/day) of vitamin D had lower rates of hip fractures or any nonvertebral fractures than participants who took 400 IU/day. Nearly all studies included calcium supplements (JAMA 2005;293:2257–64).

Differences between the RECORD trial and earlier trials may account in part for the conflicting findings, Dr. Orwoll said. In an earlier trial in France, for example, 800 IU/day of vitamin D significantly reduced fracture risk, compared with placebo in frail, elderly patients with a mean age of 85 years; all resided in group housing and had very low baseline levels of calcium and vitamin D (Osteoporosis Int. 2002;13:257–64).

Patients in the RECORD trial were a bit younger (mean age 77 years), had somewhat higher baseline levels of calcium and vitamin D, and were home-dwelling instead of institutionalized. “So calcium and vitamin D might show the most robust effect in the frailest patients,” he suggested.

Whether or not calcium and vitamin D supplements reduce fracture risk, and in which patients, remains to be seen, but they are necessary for maintaining bone mass and muscle function, Dr. Orwoll said. Most adults don't get enough calcium and vitamin D, and current recommendations on adequate vitamin D levels are too low, he added.

The Institute of Medicine in 1997 recommended vitamin D doses of 200 IU/day for adults aged 31–50 years, 400 IU/day for ages 51–70, and 600 IU/ day for older people.

A serum level of 30–35 ng/mL of 25-hydroxyvitamin D (25[OH]D) may be ideal for maximizing GI absorption of calcium and avoiding elevated parathyroid levels, Dr. Orwoll noted. A recent poll of six experts suggested that much higher doses of vitamin D supplements are needed to reach those levels. The experts said that 1,000–1,600 IU/day vitamin D would be needed to reach serum levels of 30–32 ng/mL 25(OH)D.

Vitamin D and calcium supplements are inexpensive and safe, so there's little reason not to use them, he said. Recommended daily calcium requirements are scientifically reasonable, even though they're based more on physiologic data than on clinical outcome studies.

Institute of Medicine guidelines in 1997 recommended calcium doses of 1,000 mg/day for adults aged 25–50, 1,200 mg/day for older adults, and 1,000–1,300 mg/day for pregnant or lactating women.

Vitamin D supplementation should be at least 800–1,000 IU/day, Dr. Orwoll said. For pure nutritional inadequacy, it may be appropriate to treat with a loading dose of 50,000 IU per week for 2 months followed by 1,000 IU/day, depending on baseline vitamin D levels. Vitamin D deficiency due to malabsorption or increased catabolism may require doses as high as 100,000 IU/day, he said.

SAN FRANCISCO — Recent data challenge the long-standing assumption that sufficient levels of calcium and vitamin D are fundamental in preventing and treating osteoporotic fracture, Eric S. Orwoll, M.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Calcium absorption and vitamin D levels decline with age. A number of studies over the years have solidified the idea that calcium and vitamin D supplements are effective and important in preventing osteoporosis and fractures, said Dr. Orwoll, professor of medicine at Oregon Health and Science University, Portland.

Findings from a large, well-designed study stirred up controversy when results indicated there were no differences in the rates of repeat fractures among patients with a previous fracture who took calcium, vitamin D, or calcium and vitamin D.

The investigators randomly assigned 5,292 patients aged 70 and older to one of four groups—800 IU daily oral vitamin D, 1,000 mg calcium, oral vitamin D combined with calcium, or placebo—and followed them for a median of 45 months (Lancet 2005;365:1621–8).

Among the total, 698 (13%) sustained a new low-trauma fracture. Of these, 183 (26%) were hip fractures. Investigators observed no significant differences in the incidence of new, low-trauma fractures between patients who received calcium vs. those who did not (12.6% vs. 13.7%); between those who received vitamin D₃ vs. those who did not (13.3% vs 13.1%) or between patients who received combination treatment and those who received placebo (12.6% vs. 13.4%).

Importantly, by 2 years into the Randomized Evaluation of Calcium or Vitamin D (RECORD) trial, only 55% of patients were still taking the calcium and vitamin D tablets, Dr. Orwoll noted. “This is more a compliance issue than an efficacy trial, but it's in the real world,” he said. Analysis of various subgroups could find no effects on fracture rates from the supplements.

The results contradict earlier findings. A 2003 study of 2,686 people aged 65–85 years who were vitamin D deficient found a 22% lower rate of fractures after 5 years in those who took oral vitamin D (100,000 IU every 4 months) vs. those who took placebo. A 2004 metaanalysis of five randomized, controlled trials of vitamin D for people older than 60 years found a 30% lower risk of falls in those taking vitamin D.

A 2005 metaanalysis of seven randomized trials of vitamin D supplementation with 9,820 participants showed that people taking higher doses (700–800 IU/day) of vitamin D had lower rates of hip fractures or any nonvertebral fractures than participants who took 400 IU/day. Nearly all studies included calcium supplements (JAMA 2005;293:2257–64).

Differences between the RECORD trial and earlier trials may account in part for the conflicting findings, Dr. Orwoll said. In an earlier trial in France, for example, 800 IU/day of vitamin D significantly reduced fracture risk, compared with placebo in frail, elderly patients with a mean age of 85 years; all resided in group housing and had very low baseline levels of calcium and vitamin D (Osteoporosis Int. 2002;13:257–64).

Patients in the RECORD trial were a bit younger (mean age 77 years), had somewhat higher baseline levels of calcium and vitamin D, and were home-dwelling instead of institutionalized. “So calcium and vitamin D might show the most robust effect in the frailest patients,” he suggested.

Whether or not calcium and vitamin D supplements reduce fracture risk, and in which patients, remains to be seen, but they are necessary for maintaining bone mass and muscle function, Dr. Orwoll said. Most adults don't get enough calcium and vitamin D, and current recommendations on adequate vitamin D levels are too low, he added.

The Institute of Medicine in 1997 recommended vitamin D doses of 200 IU/day for adults aged 31–50 years, 400 IU/day for ages 51–70, and 600 IU/ day for older people.

A serum level of 30–35 ng/mL of 25-hydroxyvitamin D (25[OH]D) may be ideal for maximizing GI absorption of calcium and avoiding elevated parathyroid levels, Dr. Orwoll noted. A recent poll of six experts suggested that much higher doses of vitamin D supplements are needed to reach those levels. The experts said that 1,000–1,600 IU/day vitamin D would be needed to reach serum levels of 30–32 ng/mL 25(OH)D.

Vitamin D and calcium supplements are inexpensive and safe, so there's little reason not to use them, he said. Recommended daily calcium requirements are scientifically reasonable, even though they're based more on physiologic data than on clinical outcome studies.

Institute of Medicine guidelines in 1997 recommended calcium doses of 1,000 mg/day for adults aged 25–50, 1,200 mg/day for older adults, and 1,000–1,300 mg/day for pregnant or lactating women.

Vitamin D supplementation should be at least 800–1,000 IU/day, Dr. Orwoll said. For pure nutritional inadequacy, it may be appropriate to treat with a loading dose of 50,000 IU per week for 2 months followed by 1,000 IU/day, depending on baseline vitamin D levels. Vitamin D deficiency due to malabsorption or increased catabolism may require doses as high as 100,000 IU/day, he said.

SAN FRANCISCO — A trend toward using one set of parameters to diagnose osteoporosis in both men and women hasn't caught on in the United States, where sex-specific bone density scores are the norm, Eric S. Orwoll, M.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Yet despite the ease of a gender-blind system and some persuasive data, using a sex-specific method is the way to go, at least until more data accumulate on bone loss and fracture risk in men, suggested Dr. Orwoll, professor of medicine at Oregon Health and Science University, Portland.

The evidence supporting the use of one set of parameters is mounting. Studies in recent years have shown, for example, that the 1-year risk for hip fracture overlaps in men and women with the same hip bone mineral densities. As the density gets lower, the risk for fracture increases at essentially the same rate in both sexes.

Such findings have led some bone experts to suggest that it would be easier and logical for clinicians to use just one reference range for diagnosing osteoporosis instead of using separate T scores for men and women. Bone densitometry machines in the United States currently calculate a sex-specific T score.

The International Osteoporosis Foundation in 2000 noted that the same absolute values of bone density in men and women yield the same absolute risk of vertebral or hip fracture, suggesting that using one threshold for calculating risk makes sense. The data on men are scanty, according to the statement.

Those who favor using one set of parameters usually propose using T scores that report the number of standard deviations between current bone density and the mean peak density of a 30-year-old female.

But the problem with using such a strategy, Dr. Orwoll said, is that only about 3% of older men would be identified as osteoporotic, in comparison with a young female reference population, while 19% of older men would be deemed osteoporotic if their T scores came from reference to young male norms.

About 25%–30% of older men will have a fragility fracture, but if the female reference range were used, only a small percentage of them would be identified as osteoporotic.

“So there's a little bit of incongruity in the application of the International Osteoporosis Foundation recommendations, despite the fact that they're scientifically reasonable,” he said.

Dr. Orwoll encouraged clinicians to keep using the current system of sex-specific T scores from densitometry machines until better, long-term, prospective data on fracture risk in men become available.

He added that it's also critical to include other clinical criteria besides T scores in identifying fracture risk in men.

SAN FRANCISCO — A trend toward using one set of parameters to diagnose osteoporosis in both men and women hasn't caught on in the United States, where sex-specific bone density scores are the norm, Eric S. Orwoll, M.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Yet despite the ease of a gender-blind system and some persuasive data, using a sex-specific method is the way to go, at least until more data accumulate on bone loss and fracture risk in men, suggested Dr. Orwoll, professor of medicine at Oregon Health and Science University, Portland.

The evidence supporting the use of one set of parameters is mounting. Studies in recent years have shown, for example, that the 1-year risk for hip fracture overlaps in men and women with the same hip bone mineral densities. As the density gets lower, the risk for fracture increases at essentially the same rate in both sexes.

Such findings have led some bone experts to suggest that it would be easier and logical for clinicians to use just one reference range for diagnosing osteoporosis instead of using separate T scores for men and women. Bone densitometry machines in the United States currently calculate a sex-specific T score.

The International Osteoporosis Foundation in 2000 noted that the same absolute values of bone density in men and women yield the same absolute risk of vertebral or hip fracture, suggesting that using one threshold for calculating risk makes sense. The data on men are scanty, according to the statement.

Those who favor using one set of parameters usually propose using T scores that report the number of standard deviations between current bone density and the mean peak density of a 30-year-old female.

But the problem with using such a strategy, Dr. Orwoll said, is that only about 3% of older men would be identified as osteoporotic, in comparison with a young female reference population, while 19% of older men would be deemed osteoporotic if their T scores came from reference to young male norms.

About 25%–30% of older men will have a fragility fracture, but if the female reference range were used, only a small percentage of them would be identified as osteoporotic.

“So there's a little bit of incongruity in the application of the International Osteoporosis Foundation recommendations, despite the fact that they're scientifically reasonable,” he said.

Dr. Orwoll encouraged clinicians to keep using the current system of sex-specific T scores from densitometry machines until better, long-term, prospective data on fracture risk in men become available.

He added that it's also critical to include other clinical criteria besides T scores in identifying fracture risk in men.

SAN FRANCISCO — A trend toward using one set of parameters to diagnose osteoporosis in both men and women hasn't caught on in the United States, where sex-specific bone density scores are the norm, Eric S. Orwoll, M.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

Yet despite the ease of a gender-blind system and some persuasive data, using a sex-specific method is the way to go, at least until more data accumulate on bone loss and fracture risk in men, suggested Dr. Orwoll, professor of medicine at Oregon Health and Science University, Portland.

The evidence supporting the use of one set of parameters is mounting. Studies in recent years have shown, for example, that the 1-year risk for hip fracture overlaps in men and women with the same hip bone mineral densities. As the density gets lower, the risk for fracture increases at essentially the same rate in both sexes.

Such findings have led some bone experts to suggest that it would be easier and logical for clinicians to use just one reference range for diagnosing osteoporosis instead of using separate T scores for men and women. Bone densitometry machines in the United States currently calculate a sex-specific T score.

The International Osteoporosis Foundation in 2000 noted that the same absolute values of bone density in men and women yield the same absolute risk of vertebral or hip fracture, suggesting that using one threshold for calculating risk makes sense. The data on men are scanty, according to the statement.

Those who favor using one set of parameters usually propose using T scores that report the number of standard deviations between current bone density and the mean peak density of a 30-year-old female.

But the problem with using such a strategy, Dr. Orwoll said, is that only about 3% of older men would be identified as osteoporotic, in comparison with a young female reference population, while 19% of older men would be deemed osteoporotic if their T scores came from reference to young male norms.

About 25%–30% of older men will have a fragility fracture, but if the female reference range were used, only a small percentage of them would be identified as osteoporotic.

“So there's a little bit of incongruity in the application of the International Osteoporosis Foundation recommendations, despite the fact that they're scientifically reasonable,” he said.

Dr. Orwoll encouraged clinicians to keep using the current system of sex-specific T scores from densitometry machines until better, long-term, prospective data on fracture risk in men become available.

He added that it's also critical to include other clinical criteria besides T scores in identifying fracture risk in men.

NEW ORLEANS — Giving primary care physicians quantitative information about fracture risk can help them make more judicious use of preventive drug therapy for postmenopausal women at below-average risk for osteoporosis, Joan M. Neuner, M.D., said at the annual meeting of the Society of General Internal Medicine.

In a national survey targeting a random sample of primary care physicians, those who received lifetime and 5-year quantitative fracture risk estimates along with bone mineral density (BMD) reports were less likely than those given standard BMD reports to recommend preventive prescription drugs for a 70-year-old, average-weight woman with a T score of −1.01, Dr. Neuner reported.

The survey included nationally representative proportions of general internists, family physicians, general practitioners, and ob.gyns. The physicians were asked to respond to four clinical vignettes that varied with regard to patient age, weight, and hip BMD. The survey also included Likert-scaled items to measure osteoporosis knowledge, attitudes, and screening preferences.

Of the respondents, 141 randomly received standard hip BMD measures for each vignette (reported as g/cm

Dr. Neuner and her colleagues at the Medical College of Wisconsin in Milwaukee developed a logistic regression model to adjust the results for physician specialty, physician demographics, and physician estimates of relative fracture risk for a patient with below-average risk.

“In the unadjusted analysis, physicians who received augmented BMD reports were no more or less likely to recommend prescription medications for any of the vignettes,” Dr. Neuner said. In the adjusted model, however, 25% of the physicians who received the augmented BMD would have prescribed drug therapy for the below-average-risk 70-year-old, compared with 36% of the physicians who received the standard BMD report only—a statistically significant difference, she said.

Physicians in the standard BMD group who correctly identified the woman as having a below-average risk of hip fracture based on age, weight, and hip BMD also were less likely to recommend drug therapy, she added.

The findings suggest that adding quantitative fracture risk estimates to BMD reports “has the potential to change physician prescribing behavior” for women at low risk for osteoporosis. Similarly, educating primary care providers about risk classification could change their perceptions about who should get preventive drug therapy, Dr. Neuner said.

NEW ORLEANS — Giving primary care physicians quantitative information about fracture risk can help them make more judicious use of preventive drug therapy for postmenopausal women at below-average risk for osteoporosis, Joan M. Neuner, M.D., said at the annual meeting of the Society of General Internal Medicine.

In a national survey targeting a random sample of primary care physicians, those who received lifetime and 5-year quantitative fracture risk estimates along with bone mineral density (BMD) reports were less likely than those given standard BMD reports to recommend preventive prescription drugs for a 70-year-old, average-weight woman with a T score of −1.01, Dr. Neuner reported.

The survey included nationally representative proportions of general internists, family physicians, general practitioners, and ob.gyns. The physicians were asked to respond to four clinical vignettes that varied with regard to patient age, weight, and hip BMD. The survey also included Likert-scaled items to measure osteoporosis knowledge, attitudes, and screening preferences.

Of the respondents, 141 randomly received standard hip BMD measures for each vignette (reported as g/cm

Dr. Neuner and her colleagues at the Medical College of Wisconsin in Milwaukee developed a logistic regression model to adjust the results for physician specialty, physician demographics, and physician estimates of relative fracture risk for a patient with below-average risk.

“In the unadjusted analysis, physicians who received augmented BMD reports were no more or less likely to recommend prescription medications for any of the vignettes,” Dr. Neuner said. In the adjusted model, however, 25% of the physicians who received the augmented BMD would have prescribed drug therapy for the below-average-risk 70-year-old, compared with 36% of the physicians who received the standard BMD report only—a statistically significant difference, she said.

Physicians in the standard BMD group who correctly identified the woman as having a below-average risk of hip fracture based on age, weight, and hip BMD also were less likely to recommend drug therapy, she added.

The findings suggest that adding quantitative fracture risk estimates to BMD reports “has the potential to change physician prescribing behavior” for women at low risk for osteoporosis. Similarly, educating primary care providers about risk classification could change their perceptions about who should get preventive drug therapy, Dr. Neuner said.

NEW ORLEANS — Giving primary care physicians quantitative information about fracture risk can help them make more judicious use of preventive drug therapy for postmenopausal women at below-average risk for osteoporosis, Joan M. Neuner, M.D., said at the annual meeting of the Society of General Internal Medicine.

In a national survey targeting a random sample of primary care physicians, those who received lifetime and 5-year quantitative fracture risk estimates along with bone mineral density (BMD) reports were less likely than those given standard BMD reports to recommend preventive prescription drugs for a 70-year-old, average-weight woman with a T score of −1.01, Dr. Neuner reported.

The survey included nationally representative proportions of general internists, family physicians, general practitioners, and ob.gyns. The physicians were asked to respond to four clinical vignettes that varied with regard to patient age, weight, and hip BMD. The survey also included Likert-scaled items to measure osteoporosis knowledge, attitudes, and screening preferences.

Of the respondents, 141 randomly received standard hip BMD measures for each vignette (reported as g/cm

Dr. Neuner and her colleagues at the Medical College of Wisconsin in Milwaukee developed a logistic regression model to adjust the results for physician specialty, physician demographics, and physician estimates of relative fracture risk for a patient with below-average risk.

“In the unadjusted analysis, physicians who received augmented BMD reports were no more or less likely to recommend prescription medications for any of the vignettes,” Dr. Neuner said. In the adjusted model, however, 25% of the physicians who received the augmented BMD would have prescribed drug therapy for the below-average-risk 70-year-old, compared with 36% of the physicians who received the standard BMD report only—a statistically significant difference, she said.

Physicians in the standard BMD group who correctly identified the woman as having a below-average risk of hip fracture based on age, weight, and hip BMD also were less likely to recommend drug therapy, she added.

The findings suggest that adding quantitative fracture risk estimates to BMD reports “has the potential to change physician prescribing behavior” for women at low risk for osteoporosis. Similarly, educating primary care providers about risk classification could change their perceptions about who should get preventive drug therapy, Dr. Neuner said.

SAN FRANCISCO — Patients receiving bone densitometry should be counseled about their T and their z scores, Steven T. Harris, M.D., advised at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The T score compares the patient's bone mineral density with the mean peak bone density of a 30-year-old person of the same sex and is expressed as a number of standard deviations above or below the young person's density, said Dr. Harris of the university.

The z score compares the patient's bone mineral density with mean peak density for someone the same age, and helps give patients some perspective. “In my consultative practice over the years, I've seen many, many, many patients who have been terrified by being told that they have osteoporosis at age 78 by comparing them to that 30-year-old, and yet who feel reassured when you show them where they are relative to their peers,” he said.

Sharing both score types helps give patients a more accurate picture of their bone health. A 55-year-old woman with a z score of −2 has bone density around the lower limits of normal for her age, but her T score would be −3.2 in comparison with a young adult. That patient can be reassured that she's similar to her peers, but should be persuaded that “there is an issue here that needs to be addressed,” he said.

That said, the patient with a T score above −2.5 (the cutoff for osteoporosis) can still have a clinical diagnosis of osteoporosis if other factors are present such as atraumatic vertebral fractures.

Getting a z score can be especially motivating because those patients who are abnormal compared with their peers need the greatest attention to possible secondary causes of low bone density. “If you see an abnormal z score, it makes you worry that much more about something very unusual going on in that particular patient,” he said.

Patients should also be warned that first bone density measurements give a snapshot of the skeleton's current state. But a low T score does not identify the cause of the low bone density, and the patient should not be labeled osteoporotic automatically, he added. Density reports can have a fairly wide margin of error on first-time measurements. In addition, bone density measurements often vary by a few percentage points when done by different machines. Whenever possible, follow-up scans should be performed with the same machine, he advised.

Vitamin D deficiency leading to reduced osteomalacia can produce a low T score that can improve dramatically once the vitamin deficiency is corrected. Celiac disease with malabsorption can lead to a low T score.

Individual T scores for L1-L4 on spinal densitometry are usually aggregated for diagnostic purposes instead of using the individual results for vertebral bodies. The best and worst scores for individual vertebrae should be within one standard deviation of each other. If not, one should suspect an imaging artifact. In these cases, usually the “best” T score is spurious, Dr. Harris said.

It's important to not just read the densitometry report but to look at the scan, he added. A spine with scoliosis, for example, will have changes in facet joints, making the accuracy of densitometry problematic.

Whiteness seen on the L3 and L4 sections of a spinal scan may be due to facet joint sclerosis, skewing density readings. The aggregation of L1-L4 measurements in one such patient produced a T score of −1.7, suggestive of osteopenia. But excluding the L3-L4 measurements, the T score was −2.9, in the range of osteoporosis, he said.

On hip scans, check to make sure the hip was imaged in the correct position, with the femoral shaft straight up and down and with sufficient internal rotation on the leg so that little or none of the lesser trochanter is visible. The scan should include the ischium and the greater trochanter, but the ischium should not be in the scan's femoral neck box.

SAN FRANCISCO — Patients receiving bone densitometry should be counseled about their T and their z scores, Steven T. Harris, M.D., advised at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The T score compares the patient's bone mineral density with the mean peak bone density of a 30-year-old person of the same sex and is expressed as a number of standard deviations above or below the young person's density, said Dr. Harris of the university.

The z score compares the patient's bone mineral density with mean peak density for someone the same age, and helps give patients some perspective. “In my consultative practice over the years, I've seen many, many, many patients who have been terrified by being told that they have osteoporosis at age 78 by comparing them to that 30-year-old, and yet who feel reassured when you show them where they are relative to their peers,” he said.

Sharing both score types helps give patients a more accurate picture of their bone health. A 55-year-old woman with a z score of −2 has bone density around the lower limits of normal for her age, but her T score would be −3.2 in comparison with a young adult. That patient can be reassured that she's similar to her peers, but should be persuaded that “there is an issue here that needs to be addressed,” he said.

That said, the patient with a T score above −2.5 (the cutoff for osteoporosis) can still have a clinical diagnosis of osteoporosis if other factors are present such as atraumatic vertebral fractures.

Getting a z score can be especially motivating because those patients who are abnormal compared with their peers need the greatest attention to possible secondary causes of low bone density. “If you see an abnormal z score, it makes you worry that much more about something very unusual going on in that particular patient,” he said.

Patients should also be warned that first bone density measurements give a snapshot of the skeleton's current state. But a low T score does not identify the cause of the low bone density, and the patient should not be labeled osteoporotic automatically, he added. Density reports can have a fairly wide margin of error on first-time measurements. In addition, bone density measurements often vary by a few percentage points when done by different machines. Whenever possible, follow-up scans should be performed with the same machine, he advised.

Vitamin D deficiency leading to reduced osteomalacia can produce a low T score that can improve dramatically once the vitamin deficiency is corrected. Celiac disease with malabsorption can lead to a low T score.

Individual T scores for L1-L4 on spinal densitometry are usually aggregated for diagnostic purposes instead of using the individual results for vertebral bodies. The best and worst scores for individual vertebrae should be within one standard deviation of each other. If not, one should suspect an imaging artifact. In these cases, usually the “best” T score is spurious, Dr. Harris said.

It's important to not just read the densitometry report but to look at the scan, he added. A spine with scoliosis, for example, will have changes in facet joints, making the accuracy of densitometry problematic.

Whiteness seen on the L3 and L4 sections of a spinal scan may be due to facet joint sclerosis, skewing density readings. The aggregation of L1-L4 measurements in one such patient produced a T score of −1.7, suggestive of osteopenia. But excluding the L3-L4 measurements, the T score was −2.9, in the range of osteoporosis, he said.

On hip scans, check to make sure the hip was imaged in the correct position, with the femoral shaft straight up and down and with sufficient internal rotation on the leg so that little or none of the lesser trochanter is visible. The scan should include the ischium and the greater trochanter, but the ischium should not be in the scan's femoral neck box.

SAN FRANCISCO — Patients receiving bone densitometry should be counseled about their T and their z scores, Steven T. Harris, M.D., advised at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The T score compares the patient's bone mineral density with the mean peak bone density of a 30-year-old person of the same sex and is expressed as a number of standard deviations above or below the young person's density, said Dr. Harris of the university.

The z score compares the patient's bone mineral density with mean peak density for someone the same age, and helps give patients some perspective. “In my consultative practice over the years, I've seen many, many, many patients who have been terrified by being told that they have osteoporosis at age 78 by comparing them to that 30-year-old, and yet who feel reassured when you show them where they are relative to their peers,” he said.

Sharing both score types helps give patients a more accurate picture of their bone health. A 55-year-old woman with a z score of −2 has bone density around the lower limits of normal for her age, but her T score would be −3.2 in comparison with a young adult. That patient can be reassured that she's similar to her peers, but should be persuaded that “there is an issue here that needs to be addressed,” he said.

That said, the patient with a T score above −2.5 (the cutoff for osteoporosis) can still have a clinical diagnosis of osteoporosis if other factors are present such as atraumatic vertebral fractures.

Getting a z score can be especially motivating because those patients who are abnormal compared with their peers need the greatest attention to possible secondary causes of low bone density. “If you see an abnormal z score, it makes you worry that much more about something very unusual going on in that particular patient,” he said.

Patients should also be warned that first bone density measurements give a snapshot of the skeleton's current state. But a low T score does not identify the cause of the low bone density, and the patient should not be labeled osteoporotic automatically, he added. Density reports can have a fairly wide margin of error on first-time measurements. In addition, bone density measurements often vary by a few percentage points when done by different machines. Whenever possible, follow-up scans should be performed with the same machine, he advised.

Vitamin D deficiency leading to reduced osteomalacia can produce a low T score that can improve dramatically once the vitamin deficiency is corrected. Celiac disease with malabsorption can lead to a low T score.

Individual T scores for L1-L4 on spinal densitometry are usually aggregated for diagnostic purposes instead of using the individual results for vertebral bodies. The best and worst scores for individual vertebrae should be within one standard deviation of each other. If not, one should suspect an imaging artifact. In these cases, usually the “best” T score is spurious, Dr. Harris said.

It's important to not just read the densitometry report but to look at the scan, he added. A spine with scoliosis, for example, will have changes in facet joints, making the accuracy of densitometry problematic.

Whiteness seen on the L3 and L4 sections of a spinal scan may be due to facet joint sclerosis, skewing density readings. The aggregation of L1-L4 measurements in one such patient produced a T score of −1.7, suggestive of osteopenia. But excluding the L3-L4 measurements, the T score was −2.9, in the range of osteoporosis, he said.

On hip scans, check to make sure the hip was imaged in the correct position, with the femoral shaft straight up and down and with sufficient internal rotation on the leg so that little or none of the lesser trochanter is visible. The scan should include the ischium and the greater trochanter, but the ischium should not be in the scan's femoral neck box.

SAN FRANCISCO — If the first bone density reading after starting bisphosphonate therapy shows bone loss, don't stop or alter therapy, Steven R. Cummings, M.D., advised at a meeting on osteoporosis sponsored by the University of California, San Francisco.

In all likelihood the therapy is working, but “noise” in the bone density test results in a lower density measurement. The next time the patient's bone density is taken, it probably will be higher, said Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

He and his associates analyzed data from the 6,459-patient Fracture Intervention Trial and found that among women who lost at least 4% of hip bone density in the first year of treatment with alendronate, 92% gained an average of 5% of hip bone density in the second year of therapy. The study involved postmenopausal women, aged 55–80 years, were randomized to receive alendronate at 5 mg/day for 2 years and 10 mg/day thereafter, or placebo for up to 4.5 years.

“If you were to change treatment or add another drug” after that first follow-up, “they would gain bone and you would look like a hero, but in fact they would have improved even without” any changes, he said.

Among women in the study who gained up to 4% of hip bone density in the first year on alendronate, 67% continued to gain an average of 1% bone density in the second year on therapy.

Of the women who gained a lot of hip bone—8% or more—the first year, 64% lost an average of 1% of hip bone the second year. So patients with the largest gains in bone density during the first year ought to be told: “Watch out—the next year you're likely to lose bone,” he said.

Continuing therapy also is important for reducing the risk of fracture. A comparison of the 18% of women who lost bone after a year of alendronate with the 18% of women who lost the most bone while on placebo indicated a 50% reduction in fracture risk among patients who gained bone density on treatment. A slightly greater reduction in fracture risk was seen in women who lost up to 4% of bone if they were taking alendronate, compared with placebo.

The greatest overall benefits occurred in women who lost more than 4% of bone density in the first year. In this subgroup, taking alendronate reduced the risk of fracture by 80%–90%, compared with placebo. “Stopping treatment in those patients who lose bone is exactly the wrong thing to do,” said Dr. Cummings, who is a consultant and speaker for two companies that make bisphosphonate medications.

If a patient consistently loses bone density over multiple follow-up measurements in a period of years, then it would be reasonable to reassess treatment options, he said.

SAN FRANCISCO — If the first bone density reading after starting bisphosphonate therapy shows bone loss, don't stop or alter therapy, Steven R. Cummings, M.D., advised at a meeting on osteoporosis sponsored by the University of California, San Francisco.

In all likelihood the therapy is working, but “noise” in the bone density test results in a lower density measurement. The next time the patient's bone density is taken, it probably will be higher, said Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

He and his associates analyzed data from the 6,459-patient Fracture Intervention Trial and found that among women who lost at least 4% of hip bone density in the first year of treatment with alendronate, 92% gained an average of 5% of hip bone density in the second year of therapy. The study involved postmenopausal women, aged 55–80 years, were randomized to receive alendronate at 5 mg/day for 2 years and 10 mg/day thereafter, or placebo for up to 4.5 years.

“If you were to change treatment or add another drug” after that first follow-up, “they would gain bone and you would look like a hero, but in fact they would have improved even without” any changes, he said.

Among women in the study who gained up to 4% of hip bone density in the first year on alendronate, 67% continued to gain an average of 1% bone density in the second year on therapy.

Of the women who gained a lot of hip bone—8% or more—the first year, 64% lost an average of 1% of hip bone the second year. So patients with the largest gains in bone density during the first year ought to be told: “Watch out—the next year you're likely to lose bone,” he said.

Continuing therapy also is important for reducing the risk of fracture. A comparison of the 18% of women who lost bone after a year of alendronate with the 18% of women who lost the most bone while on placebo indicated a 50% reduction in fracture risk among patients who gained bone density on treatment. A slightly greater reduction in fracture risk was seen in women who lost up to 4% of bone if they were taking alendronate, compared with placebo.

The greatest overall benefits occurred in women who lost more than 4% of bone density in the first year. In this subgroup, taking alendronate reduced the risk of fracture by 80%–90%, compared with placebo. “Stopping treatment in those patients who lose bone is exactly the wrong thing to do,” said Dr. Cummings, who is a consultant and speaker for two companies that make bisphosphonate medications.

If a patient consistently loses bone density over multiple follow-up measurements in a period of years, then it would be reasonable to reassess treatment options, he said.

SAN FRANCISCO — If the first bone density reading after starting bisphosphonate therapy shows bone loss, don't stop or alter therapy, Steven R. Cummings, M.D., advised at a meeting on osteoporosis sponsored by the University of California, San Francisco.

In all likelihood the therapy is working, but “noise” in the bone density test results in a lower density measurement. The next time the patient's bone density is taken, it probably will be higher, said Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

He and his associates analyzed data from the 6,459-patient Fracture Intervention Trial and found that among women who lost at least 4% of hip bone density in the first year of treatment with alendronate, 92% gained an average of 5% of hip bone density in the second year of therapy. The study involved postmenopausal women, aged 55–80 years, were randomized to receive alendronate at 5 mg/day for 2 years and 10 mg/day thereafter, or placebo for up to 4.5 years.

“If you were to change treatment or add another drug” after that first follow-up, “they would gain bone and you would look like a hero, but in fact they would have improved even without” any changes, he said.

Among women in the study who gained up to 4% of hip bone density in the first year on alendronate, 67% continued to gain an average of 1% bone density in the second year on therapy.

Of the women who gained a lot of hip bone—8% or more—the first year, 64% lost an average of 1% of hip bone the second year. So patients with the largest gains in bone density during the first year ought to be told: “Watch out—the next year you're likely to lose bone,” he said.

Continuing therapy also is important for reducing the risk of fracture. A comparison of the 18% of women who lost bone after a year of alendronate with the 18% of women who lost the most bone while on placebo indicated a 50% reduction in fracture risk among patients who gained bone density on treatment. A slightly greater reduction in fracture risk was seen in women who lost up to 4% of bone if they were taking alendronate, compared with placebo.

The greatest overall benefits occurred in women who lost more than 4% of bone density in the first year. In this subgroup, taking alendronate reduced the risk of fracture by 80%–90%, compared with placebo. “Stopping treatment in those patients who lose bone is exactly the wrong thing to do,” said Dr. Cummings, who is a consultant and speaker for two companies that make bisphosphonate medications.

If a patient consistently loses bone density over multiple follow-up measurements in a period of years, then it would be reasonable to reassess treatment options, he said.

SAN DIEGO — A long-term study of dehydroepiandrosterone supplementation in elderly men and women found no effect on body composition, muscle strength or performance, glucose metabolism, or quality of life.

There was a “trend … of borderline significance” for the effect of the popular supplement on bone mineral density, which was the only positive finding that approached statistical significance in the 2-year study, said K. Sreekumaran Nair, M.D., professor of endocrinology at the Mayo Medical School in Rochester, Minn.

Dr. Nair presented results of one of the few well-designed, long-term studies of dehydroepiandrosterone (DHEA) supplementation at the annual meeting of the Endocrine Society.

To provide an objective, long-term perspective, Dr. Nair and associates recruited 120 men and women (mean age, 69 and 70 years, respectively) with low dehydroepiandrosterone sulfate (DHEAS) levels, defined as concentrations below the 15th percentile for normal young adults. In men, bioavailable testosterone was also low, falling more than 1.5 standard deviations below the mean.

Eligible participants were randomized to receive supplemental DHEA (50 mg/day for women and 75 mg/day for men) or placebo for 20–24 months.

As expected, individuals taking DHEA had significant increases in DHEAS levels. Estradiol levels also rose significantly in both women and men taking DHEA. In women only, testosterone levels increased significantly, from a mean 30 ng/dL to a mean 45 ng/dL.

At enrollment and upon completion of the study, researchers conducted a wide variety of tests to identify any potential changes in muscle function, fat distribution, and carbohydrate metabolism. These tests included maximum oxygen consumption, chest press, isometric and double-knee extension, thigh muscle mass by single-slice CT, and fat-free mass by DXA to evaluate muscle function, ratio of visceral to total fat to characterize fat distribution, and fasting glucose and insulin for carbohydrate metabolism. Also measured was bone mineral density at the L2-L4 spine, femur neck, total hip, distal radius, and ultradistal radius.

Quality of life was assessed by using both physical and mental competency scores. Dr. Nair ticked through the results methodically, demonstrating “no difference at all” in subjects taking DHEA vs. placebo on myriad measures. “Body fat-free mass? The same story,” he said at one point.

Bone mineral density did improve slightly in subjects who were taking DHEA, compared with those taking placebo, mainly due to a 5.7% relative increase in ultradistal forearm BMD in women and a 2.6% relative increase in femur neck BMD in men. But Dr. Nair characterized the overall trend in BMD as “weak” evidence of DHEA's effectiveness.

On a more positive note, no adverse effects were associated with taking DHEA long term, Dr. Nair said during a symposium at the meeting.

SAN DIEGO — A long-term study of dehydroepiandrosterone supplementation in elderly men and women found no effect on body composition, muscle strength or performance, glucose metabolism, or quality of life.

There was a “trend … of borderline significance” for the effect of the popular supplement on bone mineral density, which was the only positive finding that approached statistical significance in the 2-year study, said K. Sreekumaran Nair, M.D., professor of endocrinology at the Mayo Medical School in Rochester, Minn.

Dr. Nair presented results of one of the few well-designed, long-term studies of dehydroepiandrosterone (DHEA) supplementation at the annual meeting of the Endocrine Society.

To provide an objective, long-term perspective, Dr. Nair and associates recruited 120 men and women (mean age, 69 and 70 years, respectively) with low dehydroepiandrosterone sulfate (DHEAS) levels, defined as concentrations below the 15th percentile for normal young adults. In men, bioavailable testosterone was also low, falling more than 1.5 standard deviations below the mean.

Eligible participants were randomized to receive supplemental DHEA (50 mg/day for women and 75 mg/day for men) or placebo for 20–24 months.

As expected, individuals taking DHEA had significant increases in DHEAS levels. Estradiol levels also rose significantly in both women and men taking DHEA. In women only, testosterone levels increased significantly, from a mean 30 ng/dL to a mean 45 ng/dL.

At enrollment and upon completion of the study, researchers conducted a wide variety of tests to identify any potential changes in muscle function, fat distribution, and carbohydrate metabolism. These tests included maximum oxygen consumption, chest press, isometric and double-knee extension, thigh muscle mass by single-slice CT, and fat-free mass by DXA to evaluate muscle function, ratio of visceral to total fat to characterize fat distribution, and fasting glucose and insulin for carbohydrate metabolism. Also measured was bone mineral density at the L2-L4 spine, femur neck, total hip, distal radius, and ultradistal radius.

Quality of life was assessed by using both physical and mental competency scores. Dr. Nair ticked through the results methodically, demonstrating “no difference at all” in subjects taking DHEA vs. placebo on myriad measures. “Body fat-free mass? The same story,” he said at one point.

Bone mineral density did improve slightly in subjects who were taking DHEA, compared with those taking placebo, mainly due to a 5.7% relative increase in ultradistal forearm BMD in women and a 2.6% relative increase in femur neck BMD in men. But Dr. Nair characterized the overall trend in BMD as “weak” evidence of DHEA's effectiveness.

On a more positive note, no adverse effects were associated with taking DHEA long term, Dr. Nair said during a symposium at the meeting.

SAN DIEGO — A long-term study of dehydroepiandrosterone supplementation in elderly men and women found no effect on body composition, muscle strength or performance, glucose metabolism, or quality of life.

There was a “trend … of borderline significance” for the effect of the popular supplement on bone mineral density, which was the only positive finding that approached statistical significance in the 2-year study, said K. Sreekumaran Nair, M.D., professor of endocrinology at the Mayo Medical School in Rochester, Minn.

Dr. Nair presented results of one of the few well-designed, long-term studies of dehydroepiandrosterone (DHEA) supplementation at the annual meeting of the Endocrine Society.

To provide an objective, long-term perspective, Dr. Nair and associates recruited 120 men and women (mean age, 69 and 70 years, respectively) with low dehydroepiandrosterone sulfate (DHEAS) levels, defined as concentrations below the 15th percentile for normal young adults. In men, bioavailable testosterone was also low, falling more than 1.5 standard deviations below the mean.

Eligible participants were randomized to receive supplemental DHEA (50 mg/day for women and 75 mg/day for men) or placebo for 20–24 months.

As expected, individuals taking DHEA had significant increases in DHEAS levels. Estradiol levels also rose significantly in both women and men taking DHEA. In women only, testosterone levels increased significantly, from a mean 30 ng/dL to a mean 45 ng/dL.

At enrollment and upon completion of the study, researchers conducted a wide variety of tests to identify any potential changes in muscle function, fat distribution, and carbohydrate metabolism. These tests included maximum oxygen consumption, chest press, isometric and double-knee extension, thigh muscle mass by single-slice CT, and fat-free mass by DXA to evaluate muscle function, ratio of visceral to total fat to characterize fat distribution, and fasting glucose and insulin for carbohydrate metabolism. Also measured was bone mineral density at the L2-L4 spine, femur neck, total hip, distal radius, and ultradistal radius.

Quality of life was assessed by using both physical and mental competency scores. Dr. Nair ticked through the results methodically, demonstrating “no difference at all” in subjects taking DHEA vs. placebo on myriad measures. “Body fat-free mass? The same story,” he said at one point.

Bone mineral density did improve slightly in subjects who were taking DHEA, compared with those taking placebo, mainly due to a 5.7% relative increase in ultradistal forearm BMD in women and a 2.6% relative increase in femur neck BMD in men. But Dr. Nair characterized the overall trend in BMD as “weak” evidence of DHEA's effectiveness.

On a more positive note, no adverse effects were associated with taking DHEA long term, Dr. Nair said during a symposium at the meeting.

SANTA BARBARA, CALIF. — While it's well known that bone mineral density testing should be routine for women over the age of 65, it can be difficult to decide whether to test other patients and difficult to know what to do with the results, Barbara P. Lukert, M.D., said at a symposium sponsored by the American College of Rheumatology.

The International Society for Clinical Densitometry and the National Osteoporosis Foundation list similar indications for testing bone mineral density (BMD), said Dr. Lukert of the University of Kansas Medical Center, Kansas City. While these guidelines appear straightforward, there are complexities.

The guidelines say that in addition to all women over 65, postmenopausal women under 65 with risk factors should be tested. But studies have not succeeded in identifying all of those risk factors, so in Dr. Lukert's view it's probably prudent to measure BMD in all postmenopausal women.

Premenopausal women, on the other hand, should not have their BMD measured routinely.

The guidelines also call for BMD testing in men over 70. “We know very little about the development of osteoporosis in men, except that we do know that it's much more common than we had previously thought,” Dr. Lukert said. “We aren't measuring bone density in men frequently enough.”

Similarly, the guidelines call for BMD testing in any adult who has had a fragility fracture, but in practice this is done only about 15% of the time, an oversight that Dr. Lukert described as “appalling.”

BMD testing should also be done in adults with any disease or condition associated with bone loss or low bone mass. The conditions include Cushing's disease, hyperthyroidism, hyperparathyroidism, and rheumatoid arthritis.

Some medications are associated with bone loss, most notably the glucocorticoids, and the guidelines say that any adult taking one of these medications should have BMD testing.

Any adult who's being considered for pharmacologic therapy for bone loss should have his or her BMD assessed, and anyone receiving that therapy should have BMD testing to monitor the treatment effect.

One complexity comes in interpreting the BMD results in some of these groups. For postmenopausal women one typically uses the T score, which compares the individual's BMD to a healthy young adult's. The T score is expressed in terms of the number of standard deviations the individual's BMD falls above or below this norm. The World Health Organization defines osteoporosis as a T score of -2.5 or below, and osteopenia as a T score between −1 and −2.5.

But in premenopausal women, men aged 50–64 with no risk factors, and in men aged 20–50 with risk factors, the use of T scores can be misleading. Instead, one should use the z score, which compares an individual's BMD with that of an age-matched sample. The use of T scores would imply a relationship with fracture risk that may not exist or may differ from group to group. A postmenopausal woman with a certain BMD would have many times the fracture risk of a premenopausal woman with the same BMD.

Once one has a T score or z score, the question becomes whether to treat the patient's osteoporosis or osteopenia. The National Osteoporosis Foundation recommends treating all women with a T score of -2 or below, and women with at least one additional risk factor and a T score of −1.5 or below.

On the other hand, a recent study determined that it was not cost effective to treat osteopenic women because treatment does not significantly reduce their fracture risk over a 5-year period (Ann. Intern. Med. 2005;142:734–41).

But Dr. Lukert pointed out that it's unknown whether pharmacotherapy would improve fracture risk more than 5 years down the road.

“If we start treating the patient with a T score of −2 when she is 50 years old, maybe we won't change her fracture rate in the next 5 years, but at 65 will she have a reduced risk for fracture? That is a big unknown,” she said.

SANTA BARBARA, CALIF. — While it's well known that bone mineral density testing should be routine for women over the age of 65, it can be difficult to decide whether to test other patients and difficult to know what to do with the results, Barbara P. Lukert, M.D., said at a symposium sponsored by the American College of Rheumatology.

The International Society for Clinical Densitometry and the National Osteoporosis Foundation list similar indications for testing bone mineral density (BMD), said Dr. Lukert of the University of Kansas Medical Center, Kansas City. While these guidelines appear straightforward, there are complexities.

The guidelines say that in addition to all women over 65, postmenopausal women under 65 with risk factors should be tested. But studies have not succeeded in identifying all of those risk factors, so in Dr. Lukert's view it's probably prudent to measure BMD in all postmenopausal women.

Premenopausal women, on the other hand, should not have their BMD measured routinely.

The guidelines also call for BMD testing in men over 70. “We know very little about the development of osteoporosis in men, except that we do know that it's much more common than we had previously thought,” Dr. Lukert said. “We aren't measuring bone density in men frequently enough.”

Similarly, the guidelines call for BMD testing in any adult who has had a fragility fracture, but in practice this is done only about 15% of the time, an oversight that Dr. Lukert described as “appalling.”

BMD testing should also be done in adults with any disease or condition associated with bone loss or low bone mass. The conditions include Cushing's disease, hyperthyroidism, hyperparathyroidism, and rheumatoid arthritis.

Some medications are associated with bone loss, most notably the glucocorticoids, and the guidelines say that any adult taking one of these medications should have BMD testing.

Any adult who's being considered for pharmacologic therapy for bone loss should have his or her BMD assessed, and anyone receiving that therapy should have BMD testing to monitor the treatment effect.

One complexity comes in interpreting the BMD results in some of these groups. For postmenopausal women one typically uses the T score, which compares the individual's BMD to a healthy young adult's. The T score is expressed in terms of the number of standard deviations the individual's BMD falls above or below this norm. The World Health Organization defines osteoporosis as a T score of -2.5 or below, and osteopenia as a T score between −1 and −2.5.

But in premenopausal women, men aged 50–64 with no risk factors, and in men aged 20–50 with risk factors, the use of T scores can be misleading. Instead, one should use the z score, which compares an individual's BMD with that of an age-matched sample. The use of T scores would imply a relationship with fracture risk that may not exist or may differ from group to group. A postmenopausal woman with a certain BMD would have many times the fracture risk of a premenopausal woman with the same BMD.

Once one has a T score or z score, the question becomes whether to treat the patient's osteoporosis or osteopenia. The National Osteoporosis Foundation recommends treating all women with a T score of -2 or below, and women with at least one additional risk factor and a T score of −1.5 or below.

On the other hand, a recent study determined that it was not cost effective to treat osteopenic women because treatment does not significantly reduce their fracture risk over a 5-year period (Ann. Intern. Med. 2005;142:734–41).

But Dr. Lukert pointed out that it's unknown whether pharmacotherapy would improve fracture risk more than 5 years down the road.

“If we start treating the patient with a T score of −2 when she is 50 years old, maybe we won't change her fracture rate in the next 5 years, but at 65 will she have a reduced risk for fracture? That is a big unknown,” she said.

SANTA BARBARA, CALIF. — While it's well known that bone mineral density testing should be routine for women over the age of 65, it can be difficult to decide whether to test other patients and difficult to know what to do with the results, Barbara P. Lukert, M.D., said at a symposium sponsored by the American College of Rheumatology.

The International Society for Clinical Densitometry and the National Osteoporosis Foundation list similar indications for testing bone mineral density (BMD), said Dr. Lukert of the University of Kansas Medical Center, Kansas City. While these guidelines appear straightforward, there are complexities.

The guidelines say that in addition to all women over 65, postmenopausal women under 65 with risk factors should be tested. But studies have not succeeded in identifying all of those risk factors, so in Dr. Lukert's view it's probably prudent to measure BMD in all postmenopausal women.

Premenopausal women, on the other hand, should not have their BMD measured routinely.

The guidelines also call for BMD testing in men over 70. “We know very little about the development of osteoporosis in men, except that we do know that it's much more common than we had previously thought,” Dr. Lukert said. “We aren't measuring bone density in men frequently enough.”

Similarly, the guidelines call for BMD testing in any adult who has had a fragility fracture, but in practice this is done only about 15% of the time, an oversight that Dr. Lukert described as “appalling.”

BMD testing should also be done in adults with any disease or condition associated with bone loss or low bone mass. The conditions include Cushing's disease, hyperthyroidism, hyperparathyroidism, and rheumatoid arthritis.

Some medications are associated with bone loss, most notably the glucocorticoids, and the guidelines say that any adult taking one of these medications should have BMD testing.

Any adult who's being considered for pharmacologic therapy for bone loss should have his or her BMD assessed, and anyone receiving that therapy should have BMD testing to monitor the treatment effect.

One complexity comes in interpreting the BMD results in some of these groups. For postmenopausal women one typically uses the T score, which compares the individual's BMD to a healthy young adult's. The T score is expressed in terms of the number of standard deviations the individual's BMD falls above or below this norm. The World Health Organization defines osteoporosis as a T score of -2.5 or below, and osteopenia as a T score between −1 and −2.5.

But in premenopausal women, men aged 50–64 with no risk factors, and in men aged 20–50 with risk factors, the use of T scores can be misleading. Instead, one should use the z score, which compares an individual's BMD with that of an age-matched sample. The use of T scores would imply a relationship with fracture risk that may not exist or may differ from group to group. A postmenopausal woman with a certain BMD would have many times the fracture risk of a premenopausal woman with the same BMD.

Once one has a T score or z score, the question becomes whether to treat the patient's osteoporosis or osteopenia. The National Osteoporosis Foundation recommends treating all women with a T score of -2 or below, and women with at least one additional risk factor and a T score of −1.5 or below.

On the other hand, a recent study determined that it was not cost effective to treat osteopenic women because treatment does not significantly reduce their fracture risk over a 5-year period (Ann. Intern. Med. 2005;142:734–41).

But Dr. Lukert pointed out that it's unknown whether pharmacotherapy would improve fracture risk more than 5 years down the road.

“If we start treating the patient with a T score of −2 when she is 50 years old, maybe we won't change her fracture rate in the next 5 years, but at 65 will she have a reduced risk for fracture? That is a big unknown,” she said.

SAN FRANCISCO — A yet to be released tool developed by the World Health Organization should help physicians calculate an individual's absolute risk for bone fracture and provide a basis for counseling patients regarding treatment, experts said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The expected WHO model will estimate an individual's risk of developing a fragility fracture over the next decade, based on factors that may include age, bone mineral density of the femoral neck, a history of previous fracture, family history of fracture, smoking and alcohol use, steroid use, and the presence of rheumatoid arthritis.

At this point no one knows exactly which factors will be included in the model, said Steven T. Harris, M.D., clinical professor of medicine at the University of California, San Francisco.

Calculating absolute risk for fracture greatly assists therapeutic decision-making, he said. For example, a 2001 model looked at the 10-year probability of fractures in the hip, forearm, humerus, or spine based simply on age and bone density. A 45-year-old with a T score of -3 (which is consistent with osteoporosis) has about a 10% risk of fracture over the next 10 years, but the fracture risk increases to 30% in a 75-year-old with the same bone density.

The WHO model “is going to be far better than telling someone they have osteoporosis, giving them a prescription, and saying goodbye,” Dr. Harris said. “Getting people engaged in conversation about what their risk is, and what can be done with contemporary treatment, is going to make therapy a lot more rational.”

If a clinician could tell a 55-year-old patient who is osteopenic (with a T score of -2) that the patient's absolute risk for fracture is 10% over the next 10 years, and that contemporary treatments could reduce that risk to 5%, that should help the patient decide whether the potential improvement is worth the cost or inconvenience associated with therapy.

Calculations of absolute risk also are likely to be used by insurers in the near future to decide whether to cover medical therapy for improving bone density. It may be that therapy for someone with a 20% risk of fracture will be covered, but patients with a 10% risk will have to pay for the medications themselves.

The new WHO index is due to be released “imminently,” which probably means in the first half of 2006, Steven R. Cummings, M.D., said in a separate presentation at the meeting.

He noted that the WHO's fracture risk index is based on data from about 60,000 women in 12 cohorts of patients, mostly Europeans, and needs to be validated in other populations, including that of the United States.

Some studies have been using the index to compare the value of bone density measurements with the value of other risk factors in predicting future fractures. Using the index alone without measuring bone density seems to be pretty good at predicting hip fractures, and is modestly valuable in predicting other types of osteoporotic fractures.

Having “an index of risk factors may be useful, particularly in places where you don't have bone density testing, or if you're deciding whether or not” to measure a patient's bone density, said Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

Adding bone density measurement to other factors in the index strengthens the ability to predict hip fracture and mildly strengthens the ability to predict other fractures, but the opposite does not seem to be true. “It's not clear that adding risk factors, once you know the bone density, will substantially improve the clinical judgments you can make about treatment with medication,” he said.

SAN FRANCISCO — A yet to be released tool developed by the World Health Organization should help physicians calculate an individual's absolute risk for bone fracture and provide a basis for counseling patients regarding treatment, experts said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The expected WHO model will estimate an individual's risk of developing a fragility fracture over the next decade, based on factors that may include age, bone mineral density of the femoral neck, a history of previous fracture, family history of fracture, smoking and alcohol use, steroid use, and the presence of rheumatoid arthritis.

At this point no one knows exactly which factors will be included in the model, said Steven T. Harris, M.D., clinical professor of medicine at the University of California, San Francisco.

Calculating absolute risk for fracture greatly assists therapeutic decision-making, he said. For example, a 2001 model looked at the 10-year probability of fractures in the hip, forearm, humerus, or spine based simply on age and bone density. A 45-year-old with a T score of -3 (which is consistent with osteoporosis) has about a 10% risk of fracture over the next 10 years, but the fracture risk increases to 30% in a 75-year-old with the same bone density.

The WHO model “is going to be far better than telling someone they have osteoporosis, giving them a prescription, and saying goodbye,” Dr. Harris said. “Getting people engaged in conversation about what their risk is, and what can be done with contemporary treatment, is going to make therapy a lot more rational.”

If a clinician could tell a 55-year-old patient who is osteopenic (with a T score of -2) that the patient's absolute risk for fracture is 10% over the next 10 years, and that contemporary treatments could reduce that risk to 5%, that should help the patient decide whether the potential improvement is worth the cost or inconvenience associated with therapy.

Calculations of absolute risk also are likely to be used by insurers in the near future to decide whether to cover medical therapy for improving bone density. It may be that therapy for someone with a 20% risk of fracture will be covered, but patients with a 10% risk will have to pay for the medications themselves.

The new WHO index is due to be released “imminently,” which probably means in the first half of 2006, Steven R. Cummings, M.D., said in a separate presentation at the meeting.

He noted that the WHO's fracture risk index is based on data from about 60,000 women in 12 cohorts of patients, mostly Europeans, and needs to be validated in other populations, including that of the United States.

Some studies have been using the index to compare the value of bone density measurements with the value of other risk factors in predicting future fractures. Using the index alone without measuring bone density seems to be pretty good at predicting hip fractures, and is modestly valuable in predicting other types of osteoporotic fractures.

Having “an index of risk factors may be useful, particularly in places where you don't have bone density testing, or if you're deciding whether or not” to measure a patient's bone density, said Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

Adding bone density measurement to other factors in the index strengthens the ability to predict hip fracture and mildly strengthens the ability to predict other fractures, but the opposite does not seem to be true. “It's not clear that adding risk factors, once you know the bone density, will substantially improve the clinical judgments you can make about treatment with medication,” he said.

SAN FRANCISCO — A yet to be released tool developed by the World Health Organization should help physicians calculate an individual's absolute risk for bone fracture and provide a basis for counseling patients regarding treatment, experts said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

The expected WHO model will estimate an individual's risk of developing a fragility fracture over the next decade, based on factors that may include age, bone mineral density of the femoral neck, a history of previous fracture, family history of fracture, smoking and alcohol use, steroid use, and the presence of rheumatoid arthritis.

At this point no one knows exactly which factors will be included in the model, said Steven T. Harris, M.D., clinical professor of medicine at the University of California, San Francisco.

Calculating absolute risk for fracture greatly assists therapeutic decision-making, he said. For example, a 2001 model looked at the 10-year probability of fractures in the hip, forearm, humerus, or spine based simply on age and bone density. A 45-year-old with a T score of -3 (which is consistent with osteoporosis) has about a 10% risk of fracture over the next 10 years, but the fracture risk increases to 30% in a 75-year-old with the same bone density.

The WHO model “is going to be far better than telling someone they have osteoporosis, giving them a prescription, and saying goodbye,” Dr. Harris said. “Getting people engaged in conversation about what their risk is, and what can be done with contemporary treatment, is going to make therapy a lot more rational.”

If a clinician could tell a 55-year-old patient who is osteopenic (with a T score of -2) that the patient's absolute risk for fracture is 10% over the next 10 years, and that contemporary treatments could reduce that risk to 5%, that should help the patient decide whether the potential improvement is worth the cost or inconvenience associated with therapy.

Calculations of absolute risk also are likely to be used by insurers in the near future to decide whether to cover medical therapy for improving bone density. It may be that therapy for someone with a 20% risk of fracture will be covered, but patients with a 10% risk will have to pay for the medications themselves.

The new WHO index is due to be released “imminently,” which probably means in the first half of 2006, Steven R. Cummings, M.D., said in a separate presentation at the meeting.

He noted that the WHO's fracture risk index is based on data from about 60,000 women in 12 cohorts of patients, mostly Europeans, and needs to be validated in other populations, including that of the United States.

Some studies have been using the index to compare the value of bone density measurements with the value of other risk factors in predicting future fractures. Using the index alone without measuring bone density seems to be pretty good at predicting hip fractures, and is modestly valuable in predicting other types of osteoporotic fractures.

Having “an index of risk factors may be useful, particularly in places where you don't have bone density testing, or if you're deciding whether or not” to measure a patient's bone density, said Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

Adding bone density measurement to other factors in the index strengthens the ability to predict hip fracture and mildly strengthens the ability to predict other fractures, but the opposite does not seem to be true. “It's not clear that adding risk factors, once you know the bone density, will substantially improve the clinical judgments you can make about treatment with medication,” he said.

SAN FRANCISCO — Preliminary evidence suggests that it's reasonable to give poststroke patients supplements of folate and vitamin B₁₂ to prevent fractures, Steven R. Cummings, M.D., said a meeting on osteoporosis sponsored by the University of California, San Francisco.

Supplementation also might reduce fracture risk in patients who are housebound or elderly, who might be deficient in these vitamins. “I don't yet think you can rely on this as a treatment for osteoporosis in other settings until we have more data,” added Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

He has applied for a grant to study whether these safe and inexpensive supplements might reduce fracture risk in all kinds of people, but results will not be available for at least 2 years, if he gets the grant.

Stroke doubles to quadruples the risk of subsequent hip fracture. A high homocysteine level is a risk factor for stroke and for osteoporosis in the elderly, even though it is not associated with decreased bone density, several large cohort studies have shown. Vitamin B₁₂ commonly is used with folate to suppress homocysteine concentrations.

In a Dutch study of more than 1,100 people in two cohorts, those with homocysteine levels in the highest quartile had nearly double the risk for hip fracture or nonspine fractures over a 6- to 8-year period compared with those with the lowest-quartile levels (N. Engl. J. Med. 2004;350:2033–41).

In a separate, double-blind study, approximately 559 Japanese patients who had had a stroke were randomized to 2 years of dietary supplementation with placebo or 5 mg folate/day and 1,500 mcg B₁₂/day. Homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group. The treatment group had 78% fewer hip fractures compared with the placebo group (JAMA 2005;293:1121–2).

“That is the biggest fracture reduction that I have seen yet in the field of osteoporosis. That is impressive,” Dr. Cummings said. The results are even more impressive considering that both groups showed about a 3% loss in metacarpal bone mineral density, and patients physically fell at similar rates (two per year in each group).

“These kinds of numbers make me think that this is almost too good to be true,” added Dr. Cummings. Because folate and vitamin B₁₂ are so safe and inexpensive, though, it's reasonable in the meantime to offer them to select groups of patients, he said.

No one knows how these agents might work to decrease fracture risk. “We assumed that all of the effect would be in bone density, but it's not,” he said.

Dr. Cummings and other researchers also have their eyes on another safe and inexpensive agent that might prevent and treat osteoporosis—nitrates.

A 1998 observational study found that women who took nitrates intermittently had 3%–5% higher bone mineral densities in hips and heels compared with women who did not take nitrates or took them continuously.

A separate study reported by investigators at the University of Toronto randomly assigned postmenopausal women with osteopenia or osteoporosis to take 5 mg or 20 mg of nitrates or placebo each day. After 4–6 months, measures of bone resorption decreased by 36% in the 5-mg group and by 45% in the 20-mg group, compared with placebo. “That's sort of like what you get from estrogen, and close to what you get with some bisphosphonates,” he said. Estrogen and bisphosphonates do not affect bone formation, but nitrates increased markers of bone formation by 16% and 23% compared with placebo in this study. “You might be doing double good for bone, suppressing resorption, and also stimulating bone formation” with nitrates he said.

SAN FRANCISCO — Preliminary evidence suggests that it's reasonable to give poststroke patients supplements of folate and vitamin B₁₂ to prevent fractures, Steven R. Cummings, M.D., said a meeting on osteoporosis sponsored by the University of California, San Francisco.

Supplementation also might reduce fracture risk in patients who are housebound or elderly, who might be deficient in these vitamins. “I don't yet think you can rely on this as a treatment for osteoporosis in other settings until we have more data,” added Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

He has applied for a grant to study whether these safe and inexpensive supplements might reduce fracture risk in all kinds of people, but results will not be available for at least 2 years, if he gets the grant.

Stroke doubles to quadruples the risk of subsequent hip fracture. A high homocysteine level is a risk factor for stroke and for osteoporosis in the elderly, even though it is not associated with decreased bone density, several large cohort studies have shown. Vitamin B₁₂ commonly is used with folate to suppress homocysteine concentrations.

In a Dutch study of more than 1,100 people in two cohorts, those with homocysteine levels in the highest quartile had nearly double the risk for hip fracture or nonspine fractures over a 6- to 8-year period compared with those with the lowest-quartile levels (N. Engl. J. Med. 2004;350:2033–41).

In a separate, double-blind study, approximately 559 Japanese patients who had had a stroke were randomized to 2 years of dietary supplementation with placebo or 5 mg folate/day and 1,500 mcg B₁₂/day. Homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group. The treatment group had 78% fewer hip fractures compared with the placebo group (JAMA 2005;293:1121–2).

“That is the biggest fracture reduction that I have seen yet in the field of osteoporosis. That is impressive,” Dr. Cummings said. The results are even more impressive considering that both groups showed about a 3% loss in metacarpal bone mineral density, and patients physically fell at similar rates (two per year in each group).

“These kinds of numbers make me think that this is almost too good to be true,” added Dr. Cummings. Because folate and vitamin B₁₂ are so safe and inexpensive, though, it's reasonable in the meantime to offer them to select groups of patients, he said.

No one knows how these agents might work to decrease fracture risk. “We assumed that all of the effect would be in bone density, but it's not,” he said.

Dr. Cummings and other researchers also have their eyes on another safe and inexpensive agent that might prevent and treat osteoporosis—nitrates.

A 1998 observational study found that women who took nitrates intermittently had 3%–5% higher bone mineral densities in hips and heels compared with women who did not take nitrates or took them continuously.

A separate study reported by investigators at the University of Toronto randomly assigned postmenopausal women with osteopenia or osteoporosis to take 5 mg or 20 mg of nitrates or placebo each day. After 4–6 months, measures of bone resorption decreased by 36% in the 5-mg group and by 45% in the 20-mg group, compared with placebo. “That's sort of like what you get from estrogen, and close to what you get with some bisphosphonates,” he said. Estrogen and bisphosphonates do not affect bone formation, but nitrates increased markers of bone formation by 16% and 23% compared with placebo in this study. “You might be doing double good for bone, suppressing resorption, and also stimulating bone formation” with nitrates he said.

SAN FRANCISCO — Preliminary evidence suggests that it's reasonable to give poststroke patients supplements of folate and vitamin B₁₂ to prevent fractures, Steven R. Cummings, M.D., said a meeting on osteoporosis sponsored by the University of California, San Francisco.

Supplementation also might reduce fracture risk in patients who are housebound or elderly, who might be deficient in these vitamins. “I don't yet think you can rely on this as a treatment for osteoporosis in other settings until we have more data,” added Dr. Cummings, professor emeritus of epidemiology and biostatistics at the university and director of clinical research at the California Pacific Medical Center Research Institute.

He has applied for a grant to study whether these safe and inexpensive supplements might reduce fracture risk in all kinds of people, but results will not be available for at least 2 years, if he gets the grant.

Stroke doubles to quadruples the risk of subsequent hip fracture. A high homocysteine level is a risk factor for stroke and for osteoporosis in the elderly, even though it is not associated with decreased bone density, several large cohort studies have shown. Vitamin B₁₂ commonly is used with folate to suppress homocysteine concentrations.

In a Dutch study of more than 1,100 people in two cohorts, those with homocysteine levels in the highest quartile had nearly double the risk for hip fracture or nonspine fractures over a 6- to 8-year period compared with those with the lowest-quartile levels (N. Engl. J. Med. 2004;350:2033–41).

In a separate, double-blind study, approximately 559 Japanese patients who had had a stroke were randomized to 2 years of dietary supplementation with placebo or 5 mg folate/day and 1,500 mcg B₁₂/day. Homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group. The treatment group had 78% fewer hip fractures compared with the placebo group (JAMA 2005;293:1121–2).

“That is the biggest fracture reduction that I have seen yet in the field of osteoporosis. That is impressive,” Dr. Cummings said. The results are even more impressive considering that both groups showed about a 3% loss in metacarpal bone mineral density, and patients physically fell at similar rates (two per year in each group).

“These kinds of numbers make me think that this is almost too good to be true,” added Dr. Cummings. Because folate and vitamin B₁₂ are so safe and inexpensive, though, it's reasonable in the meantime to offer them to select groups of patients, he said.

No one knows how these agents might work to decrease fracture risk. “We assumed that all of the effect would be in bone density, but it's not,” he said.

Dr. Cummings and other researchers also have their eyes on another safe and inexpensive agent that might prevent and treat osteoporosis—nitrates.

A 1998 observational study found that women who took nitrates intermittently had 3%–5% higher bone mineral densities in hips and heels compared with women who did not take nitrates or took them continuously.

A separate study reported by investigators at the University of Toronto randomly assigned postmenopausal women with osteopenia or osteoporosis to take 5 mg or 20 mg of nitrates or placebo each day. After 4–6 months, measures of bone resorption decreased by 36% in the 5-mg group and by 45% in the 20-mg group, compared with placebo. “That's sort of like what you get from estrogen, and close to what you get with some bisphosphonates,” he said. Estrogen and bisphosphonates do not affect bone formation, but nitrates increased markers of bone formation by 16% and 23% compared with placebo in this study. “You might be doing double good for bone, suppressing resorption, and also stimulating bone formation” with nitrates he said.

VIENNA — Strontium ranelate reduced the risk of new vertebral fractures by 41% over 3 years in a very-high-risk population of osteoporotic women with at least two prevalent vertebral fractures at baseline, Sergio Ortolani, M.D., reported at the annual European congress of rheumatology.

That's roughly as robust a relative risk reduction as seen in much lower-risk postmenopausal osteoporotic women with no previous vertebral fractures, noted Dr. Ortolani of the Center for Metabolic Bone Disease, Milan.

“It appears we have a new first-line treatment for postmenopausal osteoporosis,” he declared.

Dr. Ortolani presented a prespecified subgroup analysis drawn from two large phase-III multinational placebo-controlled randomized trials of strontium ranelate for the reduction of fracture risk in osteoporotic postmenopausal women. The Spinal Osteoporosis Therapeutic Intervention (SOTI) involved 1,649 women randomized to 2 g/day of oral strontium ranelate or placebo, while the Treatment of Peripheral Osteoporosis Study (TROPOS) included 5,091 women. Both Servier Laboratories-sponsored trials will run for 5 years, although the 3-year primary outcome data have been published.

Among 2,605 combined study participants without prior vertebral fractures at baseline, the 3-year incidence of new vertebral fractures was 14.4% with placebo and 7.5% with strontium ranelate, for a 48% relative risk reduction. Among the 734 participants with two or more prevalent vertebral fractures at enrollment, the absolute 3-year new vertebral fracture rates were far higher—42.7% in the placebo group, compared with 28.5% in those taking strontium ranelate—but the relative risk reduction conferred by strontium ranelate remained highly robust at 41%.

Strontium ranelate has a unique mode of action. It simultaneously increases bone formation and reduces bone resorption. The antiresorptive effect is less potent than with bisphosphonates; however, in combination with the simultaneous bone-forming effect, strontium ranelate becomes a highly effective antiosteoporosis medication, Dr. Ortolani said at the meeting sponsored by the European League Against Rheumatism.

The drug's chief adverse effect is diarrhea, which was limited to the first few months of therapy in the clinical trials. When the data from TROPOS and SOTI were pooled, there was a small but statistically significant increase in deep venous thrombosis in strontium ranelate-treated patients, but no increase in strokes or cardiovascular events. “The absolute incidence of DVT is much less than with raloxifene or estrogen replacement therapy,” Dr. Ortolani added.

Strontium ranelate is approved in several European countries and soon will be marketed throughout Europe. The Food and Drug Administration has requested that Servier conduct a U.S. clinical trial before filing for marketing approval in the United States, Dr. Ortolani said.

VIENNA — Strontium ranelate reduced the risk of new vertebral fractures by 41% over 3 years in a very-high-risk population of osteoporotic women with at least two prevalent vertebral fractures at baseline, Sergio Ortolani, M.D., reported at the annual European congress of rheumatology.

That's roughly as robust a relative risk reduction as seen in much lower-risk postmenopausal osteoporotic women with no previous vertebral fractures, noted Dr. Ortolani of the Center for Metabolic Bone Disease, Milan.

“It appears we have a new first-line treatment for postmenopausal osteoporosis,” he declared.

Dr. Ortolani presented a prespecified subgroup analysis drawn from two large phase-III multinational placebo-controlled randomized trials of strontium ranelate for the reduction of fracture risk in osteoporotic postmenopausal women. The Spinal Osteoporosis Therapeutic Intervention (SOTI) involved 1,649 women randomized to 2 g/day of oral strontium ranelate or placebo, while the Treatment of Peripheral Osteoporosis Study (TROPOS) included 5,091 women. Both Servier Laboratories-sponsored trials will run for 5 years, although the 3-year primary outcome data have been published.

Among 2,605 combined study participants without prior vertebral fractures at baseline, the 3-year incidence of new vertebral fractures was 14.4% with placebo and 7.5% with strontium ranelate, for a 48% relative risk reduction. Among the 734 participants with two or more prevalent vertebral fractures at enrollment, the absolute 3-year new vertebral fracture rates were far higher—42.7% in the placebo group, compared with 28.5% in those taking strontium ranelate—but the relative risk reduction conferred by strontium ranelate remained highly robust at 41%.

Strontium ranelate has a unique mode of action. It simultaneously increases bone formation and reduces bone resorption. The antiresorptive effect is less potent than with bisphosphonates; however, in combination with the simultaneous bone-forming effect, strontium ranelate becomes a highly effective antiosteoporosis medication, Dr. Ortolani said at the meeting sponsored by the European League Against Rheumatism.

The drug's chief adverse effect is diarrhea, which was limited to the first few months of therapy in the clinical trials. When the data from TROPOS and SOTI were pooled, there was a small but statistically significant increase in deep venous thrombosis in strontium ranelate-treated patients, but no increase in strokes or cardiovascular events. “The absolute incidence of DVT is much less than with raloxifene or estrogen replacement therapy,” Dr. Ortolani added.

Strontium ranelate is approved in several European countries and soon will be marketed throughout Europe. The Food and Drug Administration has requested that Servier conduct a U.S. clinical trial before filing for marketing approval in the United States, Dr. Ortolani said.

VIENNA — Strontium ranelate reduced the risk of new vertebral fractures by 41% over 3 years in a very-high-risk population of osteoporotic women with at least two prevalent vertebral fractures at baseline, Sergio Ortolani, M.D., reported at the annual European congress of rheumatology.

That's roughly as robust a relative risk reduction as seen in much lower-risk postmenopausal osteoporotic women with no previous vertebral fractures, noted Dr. Ortolani of the Center for Metabolic Bone Disease, Milan.

“It appears we have a new first-line treatment for postmenopausal osteoporosis,” he declared.

Dr. Ortolani presented a prespecified subgroup analysis drawn from two large phase-III multinational placebo-controlled randomized trials of strontium ranelate for the reduction of fracture risk in osteoporotic postmenopausal women. The Spinal Osteoporosis Therapeutic Intervention (SOTI) involved 1,649 women randomized to 2 g/day of oral strontium ranelate or placebo, while the Treatment of Peripheral Osteoporosis Study (TROPOS) included 5,091 women. Both Servier Laboratories-sponsored trials will run for 5 years, although the 3-year primary outcome data have been published.

Among 2,605 combined study participants without prior vertebral fractures at baseline, the 3-year incidence of new vertebral fractures was 14.4% with placebo and 7.5% with strontium ranelate, for a 48% relative risk reduction. Among the 734 participants with two or more prevalent vertebral fractures at enrollment, the absolute 3-year new vertebral fracture rates were far higher—42.7% in the placebo group, compared with 28.5% in those taking strontium ranelate—but the relative risk reduction conferred by strontium ranelate remained highly robust at 41%.

Strontium ranelate has a unique mode of action. It simultaneously increases bone formation and reduces bone resorption. The antiresorptive effect is less potent than with bisphosphonates; however, in combination with the simultaneous bone-forming effect, strontium ranelate becomes a highly effective antiosteoporosis medication, Dr. Ortolani said at the meeting sponsored by the European League Against Rheumatism.

The drug's chief adverse effect is diarrhea, which was limited to the first few months of therapy in the clinical trials. When the data from TROPOS and SOTI were pooled, there was a small but statistically significant increase in deep venous thrombosis in strontium ranelate-treated patients, but no increase in strokes or cardiovascular events. “The absolute incidence of DVT is much less than with raloxifene or estrogen replacement therapy,” Dr. Ortolani added.

Strontium ranelate is approved in several European countries and soon will be marketed throughout Europe. The Food and Drug Administration has requested that Servier conduct a U.S. clinical trial before filing for marketing approval in the United States, Dr. Ortolani said.