Osteoarthritis

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

The evidence to date is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from adverse-event reports from large, randomized, controlled trials; from a pair of small, randomized, controlled studies that specifically used bone density as an end point; and in two observational studies, said Dr. Josse, medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto.

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

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

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

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

The evidence to date is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from adverse-event reports from large, randomized, controlled trials; from a pair of small, randomized, controlled studies that specifically used bone density as an end point; and in two observational studies, said Dr. Josse, medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto.

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

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

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

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

The evidence to date is suggestive enough to prompt caution in the treatment of patients with a thiazolidinedione (TZD), Dr. Robert G. Josse said at a meeting sponsored by the American Diabetes Association.

The idea that treatment with pioglitazone (Actos) or rosiglitazone (Avandia) may cause osteoporosis and produce an increased rate of bone fractures is biologically plausible, and has been suggested in the results from adverse-event reports from large, randomized, controlled trials; from a pair of small, randomized, controlled studies that specifically used bone density as an end point; and in two observational studies, said Dr. Josse, medical director of the department of medicine at the osteoporosis center at St. Michael's Hospital in Toronto.

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

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

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

KANANASKIS, ALTA. — An investigational computer program considers more than just bone mineral density in determining fracture risk, summarizing its findings in a color-coded representation of the patient.

Developed by rheumatologist William Bensen, the Bone DESTINY software program predicts fractures more reliably than do bone mineral density (BMD) assessments alone. Using the Bone DESTINY program achieves prediction accuracy comparable with that attained by following the guidelines developed by Osteoporosis Canada (Can. Assoc. Radiol. J. 2005;56:178–88).

Bone DESTINY software is free to physicians but has not been released for general use yet. Its development has been funded by Dr. Bensen and McMaster University, Hamilton, Ont.

Bone DESTINY begins with bone density, then factors in age, steroid use, propensity to fall, history of previous falls, body mass index, and previous fragility fractures, said Dr. Maggie Larché, a rheumatologist at McMaster.

“These data are plugged into a handheld computer, which then generates a graphic with a color-coded representation of the patient's risk.” The program produces an accompanying text report.

In the first of two studies presented at the annual meeting of the Canadian Rheumatology Association, Dr. Larché and her colleagues at McMaster studied the predictive value of the software program in 14,812 postmenopausal women at least 60 years old. For each patient, treatment recommendations were produced based on BMD alone, Osteoporosis Canada guidelines, or Bone DESTINY results.

Among 7,049 patients aged 60–69 years, BMD analysis alone recommended treatment in 19%. By comparison, 20% were recommended for treatment according to OC guidelines, and 28% according to the software. In 5,252 patients aged 70–79 years, 29% were recommended for treatment based on BMD alone, 43% according to Bone DESTINY, and 51% according to OC guidelines. In 2,511 patients at least 80 years old, 47%, 72%, and 77% would be recommended for treatment according to BMD, OC guidelines, and Bone DESTINY results, respectively.

A second study compared predictive values of the three methods in 572 men and 3,914 women (aged 50 years and older) who had suffered at least one previous fragility fracture.

For all age groups, both Bone DESTINY and OC guidelines recommended treatment in 80% of the women to prevent another fracture; 35% of the women would have received treatment based on BMD alone, Dr. Larché reported.

The most significant difference, however, was observed in men, in whom Bone DESTINY recommended treatment in 73%, compared with 26% by BMD alone and 41% by OC guidelines.

Dr. Larché reported receiving honoraria and/or speakers fees from Amgen, Abbott, BMS, Pfizer, Schering, and GSK.

KANANASKIS, ALTA. — An investigational computer program considers more than just bone mineral density in determining fracture risk, summarizing its findings in a color-coded representation of the patient.

Developed by rheumatologist William Bensen, the Bone DESTINY software program predicts fractures more reliably than do bone mineral density (BMD) assessments alone. Using the Bone DESTINY program achieves prediction accuracy comparable with that attained by following the guidelines developed by Osteoporosis Canada (Can. Assoc. Radiol. J. 2005;56:178–88).

Bone DESTINY software is free to physicians but has not been released for general use yet. Its development has been funded by Dr. Bensen and McMaster University, Hamilton, Ont.

Bone DESTINY begins with bone density, then factors in age, steroid use, propensity to fall, history of previous falls, body mass index, and previous fragility fractures, said Dr. Maggie Larché, a rheumatologist at McMaster.

“These data are plugged into a handheld computer, which then generates a graphic with a color-coded representation of the patient's risk.” The program produces an accompanying text report.

In the first of two studies presented at the annual meeting of the Canadian Rheumatology Association, Dr. Larché and her colleagues at McMaster studied the predictive value of the software program in 14,812 postmenopausal women at least 60 years old. For each patient, treatment recommendations were produced based on BMD alone, Osteoporosis Canada guidelines, or Bone DESTINY results.

Among 7,049 patients aged 60–69 years, BMD analysis alone recommended treatment in 19%. By comparison, 20% were recommended for treatment according to OC guidelines, and 28% according to the software. In 5,252 patients aged 70–79 years, 29% were recommended for treatment based on BMD alone, 43% according to Bone DESTINY, and 51% according to OC guidelines. In 2,511 patients at least 80 years old, 47%, 72%, and 77% would be recommended for treatment according to BMD, OC guidelines, and Bone DESTINY results, respectively.

A second study compared predictive values of the three methods in 572 men and 3,914 women (aged 50 years and older) who had suffered at least one previous fragility fracture.

For all age groups, both Bone DESTINY and OC guidelines recommended treatment in 80% of the women to prevent another fracture; 35% of the women would have received treatment based on BMD alone, Dr. Larché reported.

The most significant difference, however, was observed in men, in whom Bone DESTINY recommended treatment in 73%, compared with 26% by BMD alone and 41% by OC guidelines.

Dr. Larché reported receiving honoraria and/or speakers fees from Amgen, Abbott, BMS, Pfizer, Schering, and GSK.

KANANASKIS, ALTA. — An investigational computer program considers more than just bone mineral density in determining fracture risk, summarizing its findings in a color-coded representation of the patient.

Developed by rheumatologist William Bensen, the Bone DESTINY software program predicts fractures more reliably than do bone mineral density (BMD) assessments alone. Using the Bone DESTINY program achieves prediction accuracy comparable with that attained by following the guidelines developed by Osteoporosis Canada (Can. Assoc. Radiol. J. 2005;56:178–88).

Bone DESTINY software is free to physicians but has not been released for general use yet. Its development has been funded by Dr. Bensen and McMaster University, Hamilton, Ont.

Bone DESTINY begins with bone density, then factors in age, steroid use, propensity to fall, history of previous falls, body mass index, and previous fragility fractures, said Dr. Maggie Larché, a rheumatologist at McMaster.

“These data are plugged into a handheld computer, which then generates a graphic with a color-coded representation of the patient's risk.” The program produces an accompanying text report.

In the first of two studies presented at the annual meeting of the Canadian Rheumatology Association, Dr. Larché and her colleagues at McMaster studied the predictive value of the software program in 14,812 postmenopausal women at least 60 years old. For each patient, treatment recommendations were produced based on BMD alone, Osteoporosis Canada guidelines, or Bone DESTINY results.

Among 7,049 patients aged 60–69 years, BMD analysis alone recommended treatment in 19%. By comparison, 20% were recommended for treatment according to OC guidelines, and 28% according to the software. In 5,252 patients aged 70–79 years, 29% were recommended for treatment based on BMD alone, 43% according to Bone DESTINY, and 51% according to OC guidelines. In 2,511 patients at least 80 years old, 47%, 72%, and 77% would be recommended for treatment according to BMD, OC guidelines, and Bone DESTINY results, respectively.

A second study compared predictive values of the three methods in 572 men and 3,914 women (aged 50 years and older) who had suffered at least one previous fragility fracture.

For all age groups, both Bone DESTINY and OC guidelines recommended treatment in 80% of the women to prevent another fracture; 35% of the women would have received treatment based on BMD alone, Dr. Larché reported.

The most significant difference, however, was observed in men, in whom Bone DESTINY recommended treatment in 73%, compared with 26% by BMD alone and 41% by OC guidelines.

Dr. Larché reported receiving honoraria and/or speakers fees from Amgen, Abbott, BMS, Pfizer, Schering, and GSK.

A genetic variant known to affect height and osteoarthritis risk has now been shown to increase the risk of nonvertebral fracture in older women, possibly because of the increased hip axis length seen in those with two copies of the gene.

“Our results suggest that the GDF5 variants target the long bones, since we find an association with hip axis length,” lead investigator Dr. Joyce van Meurs said in an interview. “This difference in hip axis length could cause a difference in fracture risk.”

Findings from the Rotterdam Study, a prospective population-based cohort of 6,114 individuals aged 55 years and over, showed that women who carried two copies of the gene were 32% more likely to experience nonvertebral fracture during the follow-up period than were noncarriers. Women with one copy of the gene had no increased risk; nor did men, regardless of their genotype, wrote Dr. van Meurs of the Erasmus Medical Centre, Rotterdam, the Netherlands, and her colleagues (Ann. Rheum. Dis. 2008 Nov. 24 [doi:10.1136/ard.2008.099655]).

The Rotterdam Study is an ongoing prospective cohort study that is examining the risks for cardiovascular, neurologic, ophthalmologic, and endocrine diseases in 15,000 subjects aged 45 years and older.

All of those in the genetic study were genotyped for rs143383. The polymorphism lies near the GDF5 gene. Mutations in this area have been linked with skeletal dysplasias, including shortening of the digits, and chondrodysplasias involving joint ankylosis.

In addition to genotyping, the subjects in the Rotterdam study underwent bone mineral density testing and radiologic assessment for osteoarthritis, and were measured for hip axis length and C-telopeptide levels. Fractures were assessed over a 10-year period.

Sixteen percent of the women and 14% of the men were homozygous carriers of rs143383; 48% of both sexes were heterozygous for the variant.

In the men there were no associations between the genotype and osteoarthritis at the hip, knee, or hand; fracture risk; or C-telopeptide levels. However, there were some significant associations among women.

Heterozygous women were 32% less likely to have osteoarthritis of the knee and hand than were noncarriers. Homozygous women were 34% less likely to have knee osteroarthritis and 48% less likely to have hand osteoarthritis than were noncarriers. Women with two copies of the gene also had significantly lower C-telopeptide levels than did noncarriers.

Among women, each copy of the gene was associated with a height increase of 0.55 cm; there was a similar, but nonsignificant, trend in men. The gene was not associated with weight or body mass index in either gender.

Nonvertebral fracture risk also was associated with rs143383 in women, but not in men. Women with two copies of the gene were 32% more likely than were noncarriers to experience a nonvertebral fracture over the follow-up period—a significant difference.

“Neither adjustment nor stratification for height and presence of osteoarthritis had an effect on the association with fracture risk,” the authors noted. “This implies that the association is not driven by any of the other observed associations, and genetic variation in the GDF5 gene seems to contribute independently to an increased fracture risk.”

The hip axis length in female homozygotes was significantly larger than that of either heterozygotes or noncarriers.

The Rotterdam Study is being funded by the European Union and national grants from the Netherlands. None of the authors declared a financial conflict with regard to the study.

A genetic variant known to affect height and osteoarthritis risk has now been shown to increase the risk of nonvertebral fracture in older women, possibly because of the increased hip axis length seen in those with two copies of the gene.

“Our results suggest that the GDF5 variants target the long bones, since we find an association with hip axis length,” lead investigator Dr. Joyce van Meurs said in an interview. “This difference in hip axis length could cause a difference in fracture risk.”

Findings from the Rotterdam Study, a prospective population-based cohort of 6,114 individuals aged 55 years and over, showed that women who carried two copies of the gene were 32% more likely to experience nonvertebral fracture during the follow-up period than were noncarriers. Women with one copy of the gene had no increased risk; nor did men, regardless of their genotype, wrote Dr. van Meurs of the Erasmus Medical Centre, Rotterdam, the Netherlands, and her colleagues (Ann. Rheum. Dis. 2008 Nov. 24 [doi:10.1136/ard.2008.099655]).

The Rotterdam Study is an ongoing prospective cohort study that is examining the risks for cardiovascular, neurologic, ophthalmologic, and endocrine diseases in 15,000 subjects aged 45 years and older.

All of those in the genetic study were genotyped for rs143383. The polymorphism lies near the GDF5 gene. Mutations in this area have been linked with skeletal dysplasias, including shortening of the digits, and chondrodysplasias involving joint ankylosis.

In addition to genotyping, the subjects in the Rotterdam study underwent bone mineral density testing and radiologic assessment for osteoarthritis, and were measured for hip axis length and C-telopeptide levels. Fractures were assessed over a 10-year period.

Sixteen percent of the women and 14% of the men were homozygous carriers of rs143383; 48% of both sexes were heterozygous for the variant.

In the men there were no associations between the genotype and osteoarthritis at the hip, knee, or hand; fracture risk; or C-telopeptide levels. However, there were some significant associations among women.

Heterozygous women were 32% less likely to have osteoarthritis of the knee and hand than were noncarriers. Homozygous women were 34% less likely to have knee osteroarthritis and 48% less likely to have hand osteoarthritis than were noncarriers. Women with two copies of the gene also had significantly lower C-telopeptide levels than did noncarriers.

Among women, each copy of the gene was associated with a height increase of 0.55 cm; there was a similar, but nonsignificant, trend in men. The gene was not associated with weight or body mass index in either gender.

Nonvertebral fracture risk also was associated with rs143383 in women, but not in men. Women with two copies of the gene were 32% more likely than were noncarriers to experience a nonvertebral fracture over the follow-up period—a significant difference.

“Neither adjustment nor stratification for height and presence of osteoarthritis had an effect on the association with fracture risk,” the authors noted. “This implies that the association is not driven by any of the other observed associations, and genetic variation in the GDF5 gene seems to contribute independently to an increased fracture risk.”

The hip axis length in female homozygotes was significantly larger than that of either heterozygotes or noncarriers.

The Rotterdam Study is being funded by the European Union and national grants from the Netherlands. None of the authors declared a financial conflict with regard to the study.

A genetic variant known to affect height and osteoarthritis risk has now been shown to increase the risk of nonvertebral fracture in older women, possibly because of the increased hip axis length seen in those with two copies of the gene.

“Our results suggest that the GDF5 variants target the long bones, since we find an association with hip axis length,” lead investigator Dr. Joyce van Meurs said in an interview. “This difference in hip axis length could cause a difference in fracture risk.”

Findings from the Rotterdam Study, a prospective population-based cohort of 6,114 individuals aged 55 years and over, showed that women who carried two copies of the gene were 32% more likely to experience nonvertebral fracture during the follow-up period than were noncarriers. Women with one copy of the gene had no increased risk; nor did men, regardless of their genotype, wrote Dr. van Meurs of the Erasmus Medical Centre, Rotterdam, the Netherlands, and her colleagues (Ann. Rheum. Dis. 2008 Nov. 24 [doi:10.1136/ard.2008.099655]).

The Rotterdam Study is an ongoing prospective cohort study that is examining the risks for cardiovascular, neurologic, ophthalmologic, and endocrine diseases in 15,000 subjects aged 45 years and older.

All of those in the genetic study were genotyped for rs143383. The polymorphism lies near the GDF5 gene. Mutations in this area have been linked with skeletal dysplasias, including shortening of the digits, and chondrodysplasias involving joint ankylosis.

In addition to genotyping, the subjects in the Rotterdam study underwent bone mineral density testing and radiologic assessment for osteoarthritis, and were measured for hip axis length and C-telopeptide levels. Fractures were assessed over a 10-year period.

Sixteen percent of the women and 14% of the men were homozygous carriers of rs143383; 48% of both sexes were heterozygous for the variant.

In the men there were no associations between the genotype and osteoarthritis at the hip, knee, or hand; fracture risk; or C-telopeptide levels. However, there were some significant associations among women.

Heterozygous women were 32% less likely to have osteoarthritis of the knee and hand than were noncarriers. Homozygous women were 34% less likely to have knee osteroarthritis and 48% less likely to have hand osteoarthritis than were noncarriers. Women with two copies of the gene also had significantly lower C-telopeptide levels than did noncarriers.

Among women, each copy of the gene was associated with a height increase of 0.55 cm; there was a similar, but nonsignificant, trend in men. The gene was not associated with weight or body mass index in either gender.

Nonvertebral fracture risk also was associated with rs143383 in women, but not in men. Women with two copies of the gene were 32% more likely than were noncarriers to experience a nonvertebral fracture over the follow-up period—a significant difference.

“Neither adjustment nor stratification for height and presence of osteoarthritis had an effect on the association with fracture risk,” the authors noted. “This implies that the association is not driven by any of the other observed associations, and genetic variation in the GDF5 gene seems to contribute independently to an increased fracture risk.”

The hip axis length in female homozygotes was significantly larger than that of either heterozygotes or noncarriers.

The Rotterdam Study is being funded by the European Union and national grants from the Netherlands. None of the authors declared a financial conflict with regard to the study.

All major low-trauma fractures, not just hip and vertebral fractures, are associated with increased mortality after age 60.

Moreover, even minor fractures—those that do not involve the pelvis, distal femur, proximal tibia, proximal humerus, or three or more ribs—raise mortality risk in the oldest patients, reported Dr. Dana Bliuc of St. Vincent's Hospital, Sydney, and associates.

The researchers assessed outcomes after low-trauma fractures in a population-based study of 4,005 men and women aged 60 years and older who were followed from 1989 through 2007. This population was almost entirely white, so the findings may not be generalizable to other ethnic groups.

A total of 952 women and 343 men sustained at least one low-trauma fracture. Death followed closely in 461 of the women and 197 of the men.

At any age, mortality was consistently higher in subjects who had sustained fractures than in the general population. Mortality was 2–4 times higher than normal for both sexes after hip fracture, approximately 2 times higher after vertebral fracture, approximately 1.5 times higher after major fracture, and approximately 1.3 times higher after minor fracture.

Mortality remained elevated for a full 5 years before returning to normal levels following all fractures. The exception was hip fractures, in which mortality remained high for up to 10 years, the investigators said (JAMA 2009;301:513–21).

Patients who sustained one fracture were at twofold to fourfold higher risk for subsequent fractures, and mortality risk rose the same amount again for another 5 years with every subsequent fracture they sustained.

“Nonhip, nonvertebral fractures, [which are] generally not even considered in these types of studies, not only constituted almost 50% of the fractures studied, but also were associated with 29% of the premature mortality,” Dr. Bluic and colleagues wrote.

“This study was not specifically designed to examine the underlying causes of mortality; however, examination of death certificates suggested no difference between causes of death in the fracture group and the general population, with cardiac, respiratory, cerebrovascular, and malignancy being the major causes.

It still remains to be determined exactly what is responsible for the increased mortality following fracture,” they added.

This study was supported in part by grants from Amgen Inc., Merck Sharp & Dohme, Sanofi-Aventis, Servier Laboratories, and Novartis.

All major low-trauma fractures, not just hip and vertebral fractures, are associated with increased mortality after age 60.

Moreover, even minor fractures—those that do not involve the pelvis, distal femur, proximal tibia, proximal humerus, or three or more ribs—raise mortality risk in the oldest patients, reported Dr. Dana Bliuc of St. Vincent's Hospital, Sydney, and associates.

The researchers assessed outcomes after low-trauma fractures in a population-based study of 4,005 men and women aged 60 years and older who were followed from 1989 through 2007. This population was almost entirely white, so the findings may not be generalizable to other ethnic groups.

A total of 952 women and 343 men sustained at least one low-trauma fracture. Death followed closely in 461 of the women and 197 of the men.

At any age, mortality was consistently higher in subjects who had sustained fractures than in the general population. Mortality was 2–4 times higher than normal for both sexes after hip fracture, approximately 2 times higher after vertebral fracture, approximately 1.5 times higher after major fracture, and approximately 1.3 times higher after minor fracture.

Mortality remained elevated for a full 5 years before returning to normal levels following all fractures. The exception was hip fractures, in which mortality remained high for up to 10 years, the investigators said (JAMA 2009;301:513–21).

Patients who sustained one fracture were at twofold to fourfold higher risk for subsequent fractures, and mortality risk rose the same amount again for another 5 years with every subsequent fracture they sustained.

“Nonhip, nonvertebral fractures, [which are] generally not even considered in these types of studies, not only constituted almost 50% of the fractures studied, but also were associated with 29% of the premature mortality,” Dr. Bluic and colleagues wrote.

“This study was not specifically designed to examine the underlying causes of mortality; however, examination of death certificates suggested no difference between causes of death in the fracture group and the general population, with cardiac, respiratory, cerebrovascular, and malignancy being the major causes.

It still remains to be determined exactly what is responsible for the increased mortality following fracture,” they added.

This study was supported in part by grants from Amgen Inc., Merck Sharp & Dohme, Sanofi-Aventis, Servier Laboratories, and Novartis.

All major low-trauma fractures, not just hip and vertebral fractures, are associated with increased mortality after age 60.

Moreover, even minor fractures—those that do not involve the pelvis, distal femur, proximal tibia, proximal humerus, or three or more ribs—raise mortality risk in the oldest patients, reported Dr. Dana Bliuc of St. Vincent's Hospital, Sydney, and associates.

The researchers assessed outcomes after low-trauma fractures in a population-based study of 4,005 men and women aged 60 years and older who were followed from 1989 through 2007. This population was almost entirely white, so the findings may not be generalizable to other ethnic groups.

A total of 952 women and 343 men sustained at least one low-trauma fracture. Death followed closely in 461 of the women and 197 of the men.

At any age, mortality was consistently higher in subjects who had sustained fractures than in the general population. Mortality was 2–4 times higher than normal for both sexes after hip fracture, approximately 2 times higher after vertebral fracture, approximately 1.5 times higher after major fracture, and approximately 1.3 times higher after minor fracture.

Mortality remained elevated for a full 5 years before returning to normal levels following all fractures. The exception was hip fractures, in which mortality remained high for up to 10 years, the investigators said (JAMA 2009;301:513–21).

Patients who sustained one fracture were at twofold to fourfold higher risk for subsequent fractures, and mortality risk rose the same amount again for another 5 years with every subsequent fracture they sustained.

“Nonhip, nonvertebral fractures, [which are] generally not even considered in these types of studies, not only constituted almost 50% of the fractures studied, but also were associated with 29% of the premature mortality,” Dr. Bluic and colleagues wrote.

“This study was not specifically designed to examine the underlying causes of mortality; however, examination of death certificates suggested no difference between causes of death in the fracture group and the general population, with cardiac, respiratory, cerebrovascular, and malignancy being the major causes.

It still remains to be determined exactly what is responsible for the increased mortality following fracture,” they added.

This study was supported in part by grants from Amgen Inc., Merck Sharp & Dohme, Sanofi-Aventis, Servier Laboratories, and Novartis.

CHICAGO — Many people who currently take or who have taken bisphosphonates are being denied essential dental procedures because of undue fears about bisphosphonate-induced osteonecrosis of the jaw, according to a specialist in oral pathology.

“The phenomenon of ONJ seen in patients who happen to be on a bisphosphonate can also be seen in patients who have never had a bisphosphonate, but whether the bisphosphonate is directly responsible for this occurrence has not been scientifically [proved],” said Ellen Eisenberg, D.M.D., head of oral and maxillofacial pathology at the University of Connecticut Health Center in Farmington.

Dr. Eisenberg, a pathologist and a consultant for Novartis, said she is unable to tell the difference between osteonecrosis of the jaw (ONJ) that has occurred in patients treated with radiation for head and neck cancer, in patients treated with intravenous or long-term oral bisphosphonates, or in patients who have not received either treatment.

“If you were to take something like 15 microscopic slides from dead bone of the jaw in such patients and ask me to tell what the difference is amongst them, I can tell you this: They all look the same,” she said.

The definitive diagnosis of bisphosphonate-associated ONJ requires exposed bone in the jaw for 8 weeks or longer. Although most cases involve a history of a surgical procedure in the mouth, most typically a tooth extraction, 40% of cases report sudden exposure of bone for no reason.

“The jaw is a high traffic area that is subject to extreme forces, and therefore it is very likely that a patient may not recall a particularly traumatic event. Nevertheless, that trauma occurred, and that preceded the exposure of the bone,” Dr. Eisenberg said at the annual Chicago Supportive Oncology Conference.

Dr. Eisenberg emphasized that the pathogenesis of ONJ is presumptive, based on the presumed alteration in the dynamic inhibition, resorption, and apposition of bone. “However, we do not know with any scientific certainty that this [presumed alteration] is, indeed, the cause,” she said.

Until results from definitive studies show that bisphosphonates, whether oral or intravenous, are indeed the cause of ONJ, it is imperative that any patient about to embark on bisphosphonate therapy get a thorough dental examination, so that any potential sites of infection or inflammatory disease can be eliminated, Dr. Eisenberg said.

Patients who develop ONJ have a host of comorbidities which may be cofactors in play. Right now, it is not scientifically sound to focus on just bisphosphonates as the cause, since there may be other reasons for developing ONJ, she maintained. For instance, patients with metastatic breast cancer or multiple myeloma suffer from widespread disease, with all of its implications, Dr. Eisenberg said.

Even older age can predispose an individual to develop ONJ, she added.

Dr. Eisenberg also suggested that a genetic polymorphism may predispose individuals to develop bisphosphonate-associated ONJ. “This is my suspicion, and it is purely conjecture, but I think that there is a subset of individuals who may be susceptible because their genetic profile predisposes them to the complication,” she said.

“What that genetic polymorphism is, I don't know, but we cannot dismiss the fact that only a very small proportion of people actually get ONJ. What is it that makes them vulnerable? Much more work needs to be done before we single out bisphosphonates as the sole cause.”

The conference is sponsored by the Journal of Supportive Oncology. The Journal of Supportive Oncology and this news organization are owned by Elsevier.

'We do not know with any scientific certainty that this [presumed alteration] is, indeed, the cause.” DR. EISENBERG

CHICAGO — Many people who currently take or who have taken bisphosphonates are being denied essential dental procedures because of undue fears about bisphosphonate-induced osteonecrosis of the jaw, according to a specialist in oral pathology.

“The phenomenon of ONJ seen in patients who happen to be on a bisphosphonate can also be seen in patients who have never had a bisphosphonate, but whether the bisphosphonate is directly responsible for this occurrence has not been scientifically [proved],” said Ellen Eisenberg, D.M.D., head of oral and maxillofacial pathology at the University of Connecticut Health Center in Farmington.

Dr. Eisenberg, a pathologist and a consultant for Novartis, said she is unable to tell the difference between osteonecrosis of the jaw (ONJ) that has occurred in patients treated with radiation for head and neck cancer, in patients treated with intravenous or long-term oral bisphosphonates, or in patients who have not received either treatment.

“If you were to take something like 15 microscopic slides from dead bone of the jaw in such patients and ask me to tell what the difference is amongst them, I can tell you this: They all look the same,” she said.

The definitive diagnosis of bisphosphonate-associated ONJ requires exposed bone in the jaw for 8 weeks or longer. Although most cases involve a history of a surgical procedure in the mouth, most typically a tooth extraction, 40% of cases report sudden exposure of bone for no reason.

“The jaw is a high traffic area that is subject to extreme forces, and therefore it is very likely that a patient may not recall a particularly traumatic event. Nevertheless, that trauma occurred, and that preceded the exposure of the bone,” Dr. Eisenberg said at the annual Chicago Supportive Oncology Conference.

Dr. Eisenberg emphasized that the pathogenesis of ONJ is presumptive, based on the presumed alteration in the dynamic inhibition, resorption, and apposition of bone. “However, we do not know with any scientific certainty that this [presumed alteration] is, indeed, the cause,” she said.

Until results from definitive studies show that bisphosphonates, whether oral or intravenous, are indeed the cause of ONJ, it is imperative that any patient about to embark on bisphosphonate therapy get a thorough dental examination, so that any potential sites of infection or inflammatory disease can be eliminated, Dr. Eisenberg said.

Patients who develop ONJ have a host of comorbidities which may be cofactors in play. Right now, it is not scientifically sound to focus on just bisphosphonates as the cause, since there may be other reasons for developing ONJ, she maintained. For instance, patients with metastatic breast cancer or multiple myeloma suffer from widespread disease, with all of its implications, Dr. Eisenberg said.

Even older age can predispose an individual to develop ONJ, she added.

Dr. Eisenberg also suggested that a genetic polymorphism may predispose individuals to develop bisphosphonate-associated ONJ. “This is my suspicion, and it is purely conjecture, but I think that there is a subset of individuals who may be susceptible because their genetic profile predisposes them to the complication,” she said.

“What that genetic polymorphism is, I don't know, but we cannot dismiss the fact that only a very small proportion of people actually get ONJ. What is it that makes them vulnerable? Much more work needs to be done before we single out bisphosphonates as the sole cause.”

The conference is sponsored by the Journal of Supportive Oncology. The Journal of Supportive Oncology and this news organization are owned by Elsevier.

'We do not know with any scientific certainty that this [presumed alteration] is, indeed, the cause.” DR. EISENBERG

CHICAGO — Many people who currently take or who have taken bisphosphonates are being denied essential dental procedures because of undue fears about bisphosphonate-induced osteonecrosis of the jaw, according to a specialist in oral pathology.

“The phenomenon of ONJ seen in patients who happen to be on a bisphosphonate can also be seen in patients who have never had a bisphosphonate, but whether the bisphosphonate is directly responsible for this occurrence has not been scientifically [proved],” said Ellen Eisenberg, D.M.D., head of oral and maxillofacial pathology at the University of Connecticut Health Center in Farmington.

Dr. Eisenberg, a pathologist and a consultant for Novartis, said she is unable to tell the difference between osteonecrosis of the jaw (ONJ) that has occurred in patients treated with radiation for head and neck cancer, in patients treated with intravenous or long-term oral bisphosphonates, or in patients who have not received either treatment.

“If you were to take something like 15 microscopic slides from dead bone of the jaw in such patients and ask me to tell what the difference is amongst them, I can tell you this: They all look the same,” she said.

The definitive diagnosis of bisphosphonate-associated ONJ requires exposed bone in the jaw for 8 weeks or longer. Although most cases involve a history of a surgical procedure in the mouth, most typically a tooth extraction, 40% of cases report sudden exposure of bone for no reason.

“The jaw is a high traffic area that is subject to extreme forces, and therefore it is very likely that a patient may not recall a particularly traumatic event. Nevertheless, that trauma occurred, and that preceded the exposure of the bone,” Dr. Eisenberg said at the annual Chicago Supportive Oncology Conference.

Dr. Eisenberg emphasized that the pathogenesis of ONJ is presumptive, based on the presumed alteration in the dynamic inhibition, resorption, and apposition of bone. “However, we do not know with any scientific certainty that this [presumed alteration] is, indeed, the cause,” she said.

Until results from definitive studies show that bisphosphonates, whether oral or intravenous, are indeed the cause of ONJ, it is imperative that any patient about to embark on bisphosphonate therapy get a thorough dental examination, so that any potential sites of infection or inflammatory disease can be eliminated, Dr. Eisenberg said.

Patients who develop ONJ have a host of comorbidities which may be cofactors in play. Right now, it is not scientifically sound to focus on just bisphosphonates as the cause, since there may be other reasons for developing ONJ, she maintained. For instance, patients with metastatic breast cancer or multiple myeloma suffer from widespread disease, with all of its implications, Dr. Eisenberg said.

Even older age can predispose an individual to develop ONJ, she added.

Dr. Eisenberg also suggested that a genetic polymorphism may predispose individuals to develop bisphosphonate-associated ONJ. “This is my suspicion, and it is purely conjecture, but I think that there is a subset of individuals who may be susceptible because their genetic profile predisposes them to the complication,” she said.

“What that genetic polymorphism is, I don't know, but we cannot dismiss the fact that only a very small proportion of people actually get ONJ. What is it that makes them vulnerable? Much more work needs to be done before we single out bisphosphonates as the sole cause.”

The conference is sponsored by the Journal of Supportive Oncology. The Journal of Supportive Oncology and this news organization are owned by Elsevier.

'We do not know with any scientific certainty that this [presumed alteration] is, indeed, the cause.” DR. EISENBERG

MONTREAL — Performance measures for the evaluation and management of osteoporosis have already been developed and soon could be making their way into clinical practice. But clinicians across specialties will need to collaborate to implement the measures and make certain that patients do not miss screening when they have a fragility fracture or other risk factors, according to several experts.

“I think we all have a consensus there is a need to improve the standard of quality of care in our patients with osteoporosis and osteoporotic fracture,” said Dr. Stuart L. Silverman, professor of clinical medicine at the University of California, Los Angeles, one of several speakers on this topic at the annual meeting of the American Society for Bone and Mineral Research.

Strategies must start at the national level but also involve specialty and primary care medical societies, hospitals, individual clinicians, and public education. Now that osteoporosis performance measures have been developed by both the Joint Commission and an American Medical Association-led coalition of societies, specialty and primary care medical societies need to develop fracture treatment advocacy statements, Dr. Silverman said.

The Joint Commission's Measures

Evidence-based monographs such as the Joint Commission's “Improving and Measuring Osteoporosis Management” are produced by expert panels with the goal of providing voluntary measures to attain in managing a disease. They are not considered standards until field-testing has ensured that measures are valid and can be obtained. The publishing of such measures as standards can “make many people feel they should be followed,” said Dr. Ethel S. Siris, professor of clinical medicine at Columbia University, New York.

“I have argued for the past couple of years that one of the reasons that we have not been more successful in getting more people evaluated and treated is because as a young field, we don't yet have an established standard of care,” Dr. Siris said.

Standards that can be established as “core measures” for hospitals and emergency departments can then become a part of the accreditation process for a hospital. Home health agencies, long-term care facilities, rehabilitation centers, and subacute care facilities, such as skilled nursing facilities, may be required to fulfill a core measure, but other care delivery settings, such as ambulatory care at a doctor's office, would not be required to maintain the standards.

Field-testing of the Joint Commission's performance measures, which were published in January, will require $380,000 over 2 years “to be validated and ultimately published as recommended standards,” she said.

Society-Backed Measures

The American Medical Association's Physician Consortium for Performance Improvement (PCPI) partnered with the American Academy of Family Physicians, the American Academy of Orthopaedic Surgeons, the American Association of Clinical Endocrinologists, the American College of Rheumatology, the Endocrine Society, and the National Committee for Quality Assurance to approve six osteoporosis performance measures in 2006. Of the 6 measures, 5 are identical or similar to 5 of the 10 measures that have been proposed by the Joint Commission. (See box.)

The PCPI measures focus primarily on outpatient management, whereas the Joint Commission document includes inpatient measures, said Dr. Kenneth G. Saag of the University of Alabama at Birmingham.

Orthopedists' Perspective

Orthopedists “have a central role in the evaluation and management of patients who sustain fragility fractures. But the problem is that we don't really fulfill the role that we could,” said Dr. Joseph D. Zuckerman of the New York University Hospital for Joint Diseases, speaking on behalf of the American Academy of Orthopaedic Surgeons.

It has been tough to get orthopedists to “buy into” evaluating and managing fragility fracture patients for osteoporosis, said Dr. Zuckerman, who chaired the AAOS Council on Education from 1999 to 2005. “They just didn't accept it as an essential part of the practice of orthopedic surgery.”

Orthopedists have cited a lack of expertise, general interest, and available consultants, as well as concerns about malpractice liability and the viewpoint of it being a medical and not a surgical problem, he said.

“We are really in the best position to initiate screening and fracture treatments, but that can only be done in a context where we have a partner or partners to work with, whether it is a rheumatologist or a primary care physician with interest in this.”

Studies have shown how orthopedists can team with other clinicians in caring for these patients. In one study, an orthopedist's participation in a standardized protocol for ordering bone mineral density testing led to a BMD evaluation in 93% of patients and initiation of treatment in 74%. In comparison, the act of sending a letter to a primary care physician that advised him or her of guidelines for osteoporosis screening had almost no impact (J. Bone Joint Surg. Am. 2008;90:953–61).

Challenges Ahead

It is hoped “that there can be some blending or melding [of the two sets of performance measures] so that we can talk about similar outcomes or processes and numerators, and similar target populations,” Dr. Silverman said.

He added that he thought that because the “measures were based on referring to fracture only,” the target population of the measures may need to change, perhaps to those defined in the new National Osteoporosis Foundation (NOF) guidelines as having low bone mass and high risk on the World Health Organization Fracture Risk Assessment Tool (FRAX).

“Should we change the wording in some of these performance measures to include these target populations as well?” Dr. Silverman asked.

The implementation of the measures as standards faces potential problems because they are not mandatory and the financial incentives for reporting them may not be worth the cost and time that is required, Dr. Silverman said. Not only may the data be hard to locate across different electronic health record systems, but the lack of reimbursement to individual hospitals for diagnosis-related groups that have been assigned for treating and diagnosing a fracture may make the measures harder to implement. The NOF has raised only $60,000 of the $380,000 that will be required to validate the Joint Commission's measures, he added.

All of the speakers disclosed relationships with companies that manufacture osteoporosis medications, including speakers bureau, consulting fees, performing paid research, and/or being on an advisory committee or other paid committee.

Proposed Osteoporosis Performance Measures

Many measures proposed by the Joint Commission are similar to those suggested by the AMA's Physician Consortium for Performance Improvement (PCPI):

▸ Screening women at risk. How many women patients aged 60–64 years with one or more risk factors, and those older than 65 years, have had at least one central DXA exam?

PCPI measurement: What percentage of female patients aged 65 years and older have had a central DXA exam ordered or performed at least once since age 60 or pharmacologic therapy prescribed within 12 months?

▸ Secondary causes. For all patients with a new diagnosis of osteoporosis, how many have had an appropriate, minimal laboratory investigation ordered or performed prior to discharge within 3 months of the initial diagnosis?

PCPI measurement: What percentage of patients aged 18 years and older with one of the following conditions or therapies has had a central DXA ordered or performed or pharmacologic therapy prescribed within 12 months: use of oral glucocorticoid therapy for greater than 3 months; aromatase therapy for breast cancer; hypogonadism; fracture history; transplant history; obesity surgery; malabsorption disease?

▸ BMD testing of glucocorticoid patients. How many patients older than 18 years who have taken oral glucocorticoids for at least 3 months have had a DXA exam ordered or performed since the initiation of therapy?

▸ Dietary education. How many patients with a diagnosis of osteoporosis or their caregivers have received information about calcium and vitamin D within the past year?

PCPI measurement: What percentage of patients, regardless of age, with a diagnosis of osteoporosis have either received both calcium and vitamin D or had documented counseling regarding both calcium and vitamin D intake, and exercise at least once within 12 months?

▸ Osteoporosis activity counseling. How many patients have received documented, age-appropriate activity information or referral for activity counseling within 36 months?

▸ Pharmacotherapy. How many patients at least 50 years old with a diagnosis of osteoporosis have been provided with pharmacotherapy within the most recent 12 months?

PCPI measurement: What percentage of patients aged 50 years and older with a diagnosis of osteoporosis were prescribed pharmacologic therapy within 12 months?

▸ Risk assessment or treatment for osteoporosis after fracture in an acute care setting. What percentage of patients aged 50 years or older with new fracture in an emergency department or a mental hospital have received a central DXA exam or a prescription for pharmacotherapy for osteoporosis prevention or treatment? (This is a potential core measure that “would have teeth,” Dr. Siris said.)

PCPI measurement: In what percentage of patients aged 50 years and older treated for a hip, spine, or distal radial fracture is there documentation of communication with the physician managing the patient's ongoing care that a fracture occurred and that the patient was or should be tested or treated for osteoporosis? (Dr. Saag noted that this is the only measure that differs from the Joint Commission's recommendations.)

▸ Risk assessment or treatment for osteoporosis after fracture in a nonacute care setting. What percentage of patients aged 50 years or older who have a documented history of a fracture within the past 3 months have received a central DXA exam or a prescription for pharmacotherapy for osteoporosis prevention or treatment?

PCPI measurement: What percentage of patients aged 50 years and older with a fracture of the hip, spine, or distal radius have had a central DXA exam ordered or performed or pharmacologic therapy prescribed?

▸ Smoking and alcohol counseling. How many patients with a diagnosis of osteoporosis or fracture have received counseling for excess alcohol consumption or smoking cessation? (This is a potential core measure.)

▸ Fall risk and personal safety education. How many patients aged 50 years or older with a new diagnosis of osteoporosis or fracture (or their caregivers) have received documented fall risk and safety education to minimize the risk of falls within 3 months of the event?

MONTREAL — Performance measures for the evaluation and management of osteoporosis have already been developed and soon could be making their way into clinical practice. But clinicians across specialties will need to collaborate to implement the measures and make certain that patients do not miss screening when they have a fragility fracture or other risk factors, according to several experts.

“I think we all have a consensus there is a need to improve the standard of quality of care in our patients with osteoporosis and osteoporotic fracture,” said Dr. Stuart L. Silverman, professor of clinical medicine at the University of California, Los Angeles, one of several speakers on this topic at the annual meeting of the American Society for Bone and Mineral Research.

Strategies must start at the national level but also involve specialty and primary care medical societies, hospitals, individual clinicians, and public education. Now that osteoporosis performance measures have been developed by both the Joint Commission and an American Medical Association-led coalition of societies, specialty and primary care medical societies need to develop fracture treatment advocacy statements, Dr. Silverman said.

The Joint Commission's Measures

Evidence-based monographs such as the Joint Commission's “Improving and Measuring Osteoporosis Management” are produced by expert panels with the goal of providing voluntary measures to attain in managing a disease. They are not considered standards until field-testing has ensured that measures are valid and can be obtained. The publishing of such measures as standards can “make many people feel they should be followed,” said Dr. Ethel S. Siris, professor of clinical medicine at Columbia University, New York.

“I have argued for the past couple of years that one of the reasons that we have not been more successful in getting more people evaluated and treated is because as a young field, we don't yet have an established standard of care,” Dr. Siris said.

Standards that can be established as “core measures” for hospitals and emergency departments can then become a part of the accreditation process for a hospital. Home health agencies, long-term care facilities, rehabilitation centers, and subacute care facilities, such as skilled nursing facilities, may be required to fulfill a core measure, but other care delivery settings, such as ambulatory care at a doctor's office, would not be required to maintain the standards.

Field-testing of the Joint Commission's performance measures, which were published in January, will require $380,000 over 2 years “to be validated and ultimately published as recommended standards,” she said.

Society-Backed Measures

The American Medical Association's Physician Consortium for Performance Improvement (PCPI) partnered with the American Academy of Family Physicians, the American Academy of Orthopaedic Surgeons, the American Association of Clinical Endocrinologists, the American College of Rheumatology, the Endocrine Society, and the National Committee for Quality Assurance to approve six osteoporosis performance measures in 2006. Of the 6 measures, 5 are identical or similar to 5 of the 10 measures that have been proposed by the Joint Commission. (See box.)

The PCPI measures focus primarily on outpatient management, whereas the Joint Commission document includes inpatient measures, said Dr. Kenneth G. Saag of the University of Alabama at Birmingham.

Orthopedists' Perspective

Orthopedists “have a central role in the evaluation and management of patients who sustain fragility fractures. But the problem is that we don't really fulfill the role that we could,” said Dr. Joseph D. Zuckerman of the New York University Hospital for Joint Diseases, speaking on behalf of the American Academy of Orthopaedic Surgeons.

It has been tough to get orthopedists to “buy into” evaluating and managing fragility fracture patients for osteoporosis, said Dr. Zuckerman, who chaired the AAOS Council on Education from 1999 to 2005. “They just didn't accept it as an essential part of the practice of orthopedic surgery.”

Orthopedists have cited a lack of expertise, general interest, and available consultants, as well as concerns about malpractice liability and the viewpoint of it being a medical and not a surgical problem, he said.

“We are really in the best position to initiate screening and fracture treatments, but that can only be done in a context where we have a partner or partners to work with, whether it is a rheumatologist or a primary care physician with interest in this.”

Studies have shown how orthopedists can team with other clinicians in caring for these patients. In one study, an orthopedist's participation in a standardized protocol for ordering bone mineral density testing led to a BMD evaluation in 93% of patients and initiation of treatment in 74%. In comparison, the act of sending a letter to a primary care physician that advised him or her of guidelines for osteoporosis screening had almost no impact (J. Bone Joint Surg. Am. 2008;90:953–61).

Challenges Ahead

It is hoped “that there can be some blending or melding [of the two sets of performance measures] so that we can talk about similar outcomes or processes and numerators, and similar target populations,” Dr. Silverman said.

He added that he thought that because the “measures were based on referring to fracture only,” the target population of the measures may need to change, perhaps to those defined in the new National Osteoporosis Foundation (NOF) guidelines as having low bone mass and high risk on the World Health Organization Fracture Risk Assessment Tool (FRAX).

“Should we change the wording in some of these performance measures to include these target populations as well?” Dr. Silverman asked.

The implementation of the measures as standards faces potential problems because they are not mandatory and the financial incentives for reporting them may not be worth the cost and time that is required, Dr. Silverman said. Not only may the data be hard to locate across different electronic health record systems, but the lack of reimbursement to individual hospitals for diagnosis-related groups that have been assigned for treating and diagnosing a fracture may make the measures harder to implement. The NOF has raised only $60,000 of the $380,000 that will be required to validate the Joint Commission's measures, he added.

All of the speakers disclosed relationships with companies that manufacture osteoporosis medications, including speakers bureau, consulting fees, performing paid research, and/or being on an advisory committee or other paid committee.

Proposed Osteoporosis Performance Measures

Many measures proposed by the Joint Commission are similar to those suggested by the AMA's Physician Consortium for Performance Improvement (PCPI):

▸ Screening women at risk. How many women patients aged 60–64 years with one or more risk factors, and those older than 65 years, have had at least one central DXA exam?

PCPI measurement: What percentage of female patients aged 65 years and older have had a central DXA exam ordered or performed at least once since age 60 or pharmacologic therapy prescribed within 12 months?

▸ Secondary causes. For all patients with a new diagnosis of osteoporosis, how many have had an appropriate, minimal laboratory investigation ordered or performed prior to discharge within 3 months of the initial diagnosis?

PCPI measurement: What percentage of patients aged 18 years and older with one of the following conditions or therapies has had a central DXA ordered or performed or pharmacologic therapy prescribed within 12 months: use of oral glucocorticoid therapy for greater than 3 months; aromatase therapy for breast cancer; hypogonadism; fracture history; transplant history; obesity surgery; malabsorption disease?

▸ BMD testing of glucocorticoid patients. How many patients older than 18 years who have taken oral glucocorticoids for at least 3 months have had a DXA exam ordered or performed since the initiation of therapy?

▸ Dietary education. How many patients with a diagnosis of osteoporosis or their caregivers have received information about calcium and vitamin D within the past year?

PCPI measurement: What percentage of patients, regardless of age, with a diagnosis of osteoporosis have either received both calcium and vitamin D or had documented counseling regarding both calcium and vitamin D intake, and exercise at least once within 12 months?

▸ Osteoporosis activity counseling. How many patients have received documented, age-appropriate activity information or referral for activity counseling within 36 months?

▸ Pharmacotherapy. How many patients at least 50 years old with a diagnosis of osteoporosis have been provided with pharmacotherapy within the most recent 12 months?

PCPI measurement: What percentage of patients aged 50 years and older with a diagnosis of osteoporosis were prescribed pharmacologic therapy within 12 months?

▸ Risk assessment or treatment for osteoporosis after fracture in an acute care setting. What percentage of patients aged 50 years or older with new fracture in an emergency department or a mental hospital have received a central DXA exam or a prescription for pharmacotherapy for osteoporosis prevention or treatment? (This is a potential core measure that “would have teeth,” Dr. Siris said.)

PCPI measurement: In what percentage of patients aged 50 years and older treated for a hip, spine, or distal radial fracture is there documentation of communication with the physician managing the patient's ongoing care that a fracture occurred and that the patient was or should be tested or treated for osteoporosis? (Dr. Saag noted that this is the only measure that differs from the Joint Commission's recommendations.)

▸ Risk assessment or treatment for osteoporosis after fracture in a nonacute care setting. What percentage of patients aged 50 years or older who have a documented history of a fracture within the past 3 months have received a central DXA exam or a prescription for pharmacotherapy for osteoporosis prevention or treatment?

PCPI measurement: What percentage of patients aged 50 years and older with a fracture of the hip, spine, or distal radius have had a central DXA exam ordered or performed or pharmacologic therapy prescribed?

▸ Smoking and alcohol counseling. How many patients with a diagnosis of osteoporosis or fracture have received counseling for excess alcohol consumption or smoking cessation? (This is a potential core measure.)

▸ Fall risk and personal safety education. How many patients aged 50 years or older with a new diagnosis of osteoporosis or fracture (or their caregivers) have received documented fall risk and safety education to minimize the risk of falls within 3 months of the event?

MONTREAL — Performance measures for the evaluation and management of osteoporosis have already been developed and soon could be making their way into clinical practice. But clinicians across specialties will need to collaborate to implement the measures and make certain that patients do not miss screening when they have a fragility fracture or other risk factors, according to several experts.

“I think we all have a consensus there is a need to improve the standard of quality of care in our patients with osteoporosis and osteoporotic fracture,” said Dr. Stuart L. Silverman, professor of clinical medicine at the University of California, Los Angeles, one of several speakers on this topic at the annual meeting of the American Society for Bone and Mineral Research.

Strategies must start at the national level but also involve specialty and primary care medical societies, hospitals, individual clinicians, and public education. Now that osteoporosis performance measures have been developed by both the Joint Commission and an American Medical Association-led coalition of societies, specialty and primary care medical societies need to develop fracture treatment advocacy statements, Dr. Silverman said.

The Joint Commission's Measures

Evidence-based monographs such as the Joint Commission's “Improving and Measuring Osteoporosis Management” are produced by expert panels with the goal of providing voluntary measures to attain in managing a disease. They are not considered standards until field-testing has ensured that measures are valid and can be obtained. The publishing of such measures as standards can “make many people feel they should be followed,” said Dr. Ethel S. Siris, professor of clinical medicine at Columbia University, New York.

“I have argued for the past couple of years that one of the reasons that we have not been more successful in getting more people evaluated and treated is because as a young field, we don't yet have an established standard of care,” Dr. Siris said.

Standards that can be established as “core measures” for hospitals and emergency departments can then become a part of the accreditation process for a hospital. Home health agencies, long-term care facilities, rehabilitation centers, and subacute care facilities, such as skilled nursing facilities, may be required to fulfill a core measure, but other care delivery settings, such as ambulatory care at a doctor's office, would not be required to maintain the standards.

Field-testing of the Joint Commission's performance measures, which were published in January, will require $380,000 over 2 years “to be validated and ultimately published as recommended standards,” she said.

Society-Backed Measures

The American Medical Association's Physician Consortium for Performance Improvement (PCPI) partnered with the American Academy of Family Physicians, the American Academy of Orthopaedic Surgeons, the American Association of Clinical Endocrinologists, the American College of Rheumatology, the Endocrine Society, and the National Committee for Quality Assurance to approve six osteoporosis performance measures in 2006. Of the 6 measures, 5 are identical or similar to 5 of the 10 measures that have been proposed by the Joint Commission. (See box.)

The PCPI measures focus primarily on outpatient management, whereas the Joint Commission document includes inpatient measures, said Dr. Kenneth G. Saag of the University of Alabama at Birmingham.

Orthopedists' Perspective

Orthopedists “have a central role in the evaluation and management of patients who sustain fragility fractures. But the problem is that we don't really fulfill the role that we could,” said Dr. Joseph D. Zuckerman of the New York University Hospital for Joint Diseases, speaking on behalf of the American Academy of Orthopaedic Surgeons.

It has been tough to get orthopedists to “buy into” evaluating and managing fragility fracture patients for osteoporosis, said Dr. Zuckerman, who chaired the AAOS Council on Education from 1999 to 2005. “They just didn't accept it as an essential part of the practice of orthopedic surgery.”

Orthopedists have cited a lack of expertise, general interest, and available consultants, as well as concerns about malpractice liability and the viewpoint of it being a medical and not a surgical problem, he said.

“We are really in the best position to initiate screening and fracture treatments, but that can only be done in a context where we have a partner or partners to work with, whether it is a rheumatologist or a primary care physician with interest in this.”

Studies have shown how orthopedists can team with other clinicians in caring for these patients. In one study, an orthopedist's participation in a standardized protocol for ordering bone mineral density testing led to a BMD evaluation in 93% of patients and initiation of treatment in 74%. In comparison, the act of sending a letter to a primary care physician that advised him or her of guidelines for osteoporosis screening had almost no impact (J. Bone Joint Surg. Am. 2008;90:953–61).

Challenges Ahead

It is hoped “that there can be some blending or melding [of the two sets of performance measures] so that we can talk about similar outcomes or processes and numerators, and similar target populations,” Dr. Silverman said.

He added that he thought that because the “measures were based on referring to fracture only,” the target population of the measures may need to change, perhaps to those defined in the new National Osteoporosis Foundation (NOF) guidelines as having low bone mass and high risk on the World Health Organization Fracture Risk Assessment Tool (FRAX).

“Should we change the wording in some of these performance measures to include these target populations as well?” Dr. Silverman asked.

The implementation of the measures as standards faces potential problems because they are not mandatory and the financial incentives for reporting them may not be worth the cost and time that is required, Dr. Silverman said. Not only may the data be hard to locate across different electronic health record systems, but the lack of reimbursement to individual hospitals for diagnosis-related groups that have been assigned for treating and diagnosing a fracture may make the measures harder to implement. The NOF has raised only $60,000 of the $380,000 that will be required to validate the Joint Commission's measures, he added.

All of the speakers disclosed relationships with companies that manufacture osteoporosis medications, including speakers bureau, consulting fees, performing paid research, and/or being on an advisory committee or other paid committee.

Proposed Osteoporosis Performance Measures

Many measures proposed by the Joint Commission are similar to those suggested by the AMA's Physician Consortium for Performance Improvement (PCPI):

▸ Screening women at risk. How many women patients aged 60–64 years with one or more risk factors, and those older than 65 years, have had at least one central DXA exam?

PCPI measurement: What percentage of female patients aged 65 years and older have had a central DXA exam ordered or performed at least once since age 60 or pharmacologic therapy prescribed within 12 months?

▸ Secondary causes. For all patients with a new diagnosis of osteoporosis, how many have had an appropriate, minimal laboratory investigation ordered or performed prior to discharge within 3 months of the initial diagnosis?

PCPI measurement: What percentage of patients aged 18 years and older with one of the following conditions or therapies has had a central DXA ordered or performed or pharmacologic therapy prescribed within 12 months: use of oral glucocorticoid therapy for greater than 3 months; aromatase therapy for breast cancer; hypogonadism; fracture history; transplant history; obesity surgery; malabsorption disease?

▸ BMD testing of glucocorticoid patients. How many patients older than 18 years who have taken oral glucocorticoids for at least 3 months have had a DXA exam ordered or performed since the initiation of therapy?

▸ Dietary education. How many patients with a diagnosis of osteoporosis or their caregivers have received information about calcium and vitamin D within the past year?

PCPI measurement: What percentage of patients, regardless of age, with a diagnosis of osteoporosis have either received both calcium and vitamin D or had documented counseling regarding both calcium and vitamin D intake, and exercise at least once within 12 months?

▸ Osteoporosis activity counseling. How many patients have received documented, age-appropriate activity information or referral for activity counseling within 36 months?

▸ Pharmacotherapy. How many patients at least 50 years old with a diagnosis of osteoporosis have been provided with pharmacotherapy within the most recent 12 months?

PCPI measurement: What percentage of patients aged 50 years and older with a diagnosis of osteoporosis were prescribed pharmacologic therapy within 12 months?

▸ Risk assessment or treatment for osteoporosis after fracture in an acute care setting. What percentage of patients aged 50 years or older with new fracture in an emergency department or a mental hospital have received a central DXA exam or a prescription for pharmacotherapy for osteoporosis prevention or treatment? (This is a potential core measure that “would have teeth,” Dr. Siris said.)

PCPI measurement: In what percentage of patients aged 50 years and older treated for a hip, spine, or distal radial fracture is there documentation of communication with the physician managing the patient's ongoing care that a fracture occurred and that the patient was or should be tested or treated for osteoporosis? (Dr. Saag noted that this is the only measure that differs from the Joint Commission's recommendations.)

▸ Risk assessment or treatment for osteoporosis after fracture in a nonacute care setting. What percentage of patients aged 50 years or older who have a documented history of a fracture within the past 3 months have received a central DXA exam or a prescription for pharmacotherapy for osteoporosis prevention or treatment?

PCPI measurement: What percentage of patients aged 50 years and older with a fracture of the hip, spine, or distal radius have had a central DXA exam ordered or performed or pharmacologic therapy prescribed?

▸ Smoking and alcohol counseling. How many patients with a diagnosis of osteoporosis or fracture have received counseling for excess alcohol consumption or smoking cessation? (This is a potential core measure.)

▸ Fall risk and personal safety education. How many patients aged 50 years or older with a new diagnosis of osteoporosis or fracture (or their caregivers) have received documented fall risk and safety education to minimize the risk of falls within 3 months of the event?

MONTREAL — The clinical risk factors of age and bone mineral density at the hip appear to predict the probability of a hip fracture or a major osteoporotic fracture significantly better than the World Health Organization's more complex Fracture Risk Assessment Tool, according to an analysis of data from a prospective study of 6,252 older white women.

The results suggest that “the addition of [complex] clinical risk factor information to age and BMD alone does not enhance the prediction of these fractures in older women,” said Dr. Kristine E. Ensrud, professor of medicine at the University of Minnesota, Minneapolis.

The FRAX algorithm is designed to predict only the 10-year probability of a hip fracture or a major osteoporotic fracture. It builds a risk profile based on nine clinical risk factors (age, sex, prior history of fracture, oral glucocorticoid use, presence of rheumatoid arthritis, parental history of hip fracture, smoking status, alcohol consumption, and body mass index).

Dr. Ensrud and her colleagues used data from 6,252 participants in the Study of Osteoporotic Fractures, which enrolled women during 1986–1988. Hip BMD measurements and all of the FRAX clinical risk factors were available for these women, who had an average age of 71 years. Incident fractures were confirmed in 98% of cases reported during the study's 10-year follow-up period.

A combination of age and hip BMD had significantly greater ability to predict the 10-year risk of a hip fracture than did the FRAX algorithm alone, based on area-under-the-curve (AUC) statistics that the investigators calculated from receiver operating characteristic curves that were built with data from the study. However, the AUC statistic that was derived from the age-plus-hip-BMD model (0.76) was similar to that obtained with FRAX plus hip BMD (0.75). The AUC statistic for FRAX alone was 0.71. (An AUC of 0.50 reflects a predictive ability equal to chance.)

Similarly, age plus hip BMD had a significantly greater ability to predict both major osteoporotic fractures (hip, clinical spine, wrist, or humerus) and clinical fractures (defined as nonvertebral or clinical vertebral fractures) than did the FRAX algorithm alone, Dr. Ensrud reported at the annual meeting of the American Society for Bone and Mineral Research.

To refine their analysis further, Dr. Ensrud and her associates compared the proportion of women across the models who were classified in the highest decile of fracture risk and who actually experienced a fracture outcome. This type of assessment enhances the clinical usefulness of a risk prediction model because it contains a higher proportion of women who actually experienced the outcome in question, she said.

This simple model of age and prior fracture history (rather than hip BMD) also predicted the 10-year risk of hip, osteoporotic, and clinical fractures just as well as the FRAX algorithm alone did. This finding suggests that “in a setting where BMD is not available, the addition of [complex] clinical risk factor information to age and prior fracture history alone does not enhance the prediction of these fractures in older women,” Dr. Ensrud said.

The study was funded by the National Institute on Aging.

MONTREAL — The clinical risk factors of age and bone mineral density at the hip appear to predict the probability of a hip fracture or a major osteoporotic fracture significantly better than the World Health Organization's more complex Fracture Risk Assessment Tool, according to an analysis of data from a prospective study of 6,252 older white women.

The results suggest that “the addition of [complex] clinical risk factor information to age and BMD alone does not enhance the prediction of these fractures in older women,” said Dr. Kristine E. Ensrud, professor of medicine at the University of Minnesota, Minneapolis.

The FRAX algorithm is designed to predict only the 10-year probability of a hip fracture or a major osteoporotic fracture. It builds a risk profile based on nine clinical risk factors (age, sex, prior history of fracture, oral glucocorticoid use, presence of rheumatoid arthritis, parental history of hip fracture, smoking status, alcohol consumption, and body mass index).

Dr. Ensrud and her colleagues used data from 6,252 participants in the Study of Osteoporotic Fractures, which enrolled women during 1986–1988. Hip BMD measurements and all of the FRAX clinical risk factors were available for these women, who had an average age of 71 years. Incident fractures were confirmed in 98% of cases reported during the study's 10-year follow-up period.

A combination of age and hip BMD had significantly greater ability to predict the 10-year risk of a hip fracture than did the FRAX algorithm alone, based on area-under-the-curve (AUC) statistics that the investigators calculated from receiver operating characteristic curves that were built with data from the study. However, the AUC statistic that was derived from the age-plus-hip-BMD model (0.76) was similar to that obtained with FRAX plus hip BMD (0.75). The AUC statistic for FRAX alone was 0.71. (An AUC of 0.50 reflects a predictive ability equal to chance.)

Similarly, age plus hip BMD had a significantly greater ability to predict both major osteoporotic fractures (hip, clinical spine, wrist, or humerus) and clinical fractures (defined as nonvertebral or clinical vertebral fractures) than did the FRAX algorithm alone, Dr. Ensrud reported at the annual meeting of the American Society for Bone and Mineral Research.

To refine their analysis further, Dr. Ensrud and her associates compared the proportion of women across the models who were classified in the highest decile of fracture risk and who actually experienced a fracture outcome. This type of assessment enhances the clinical usefulness of a risk prediction model because it contains a higher proportion of women who actually experienced the outcome in question, she said.

This simple model of age and prior fracture history (rather than hip BMD) also predicted the 10-year risk of hip, osteoporotic, and clinical fractures just as well as the FRAX algorithm alone did. This finding suggests that “in a setting where BMD is not available, the addition of [complex] clinical risk factor information to age and prior fracture history alone does not enhance the prediction of these fractures in older women,” Dr. Ensrud said.

The study was funded by the National Institute on Aging.

MONTREAL — The clinical risk factors of age and bone mineral density at the hip appear to predict the probability of a hip fracture or a major osteoporotic fracture significantly better than the World Health Organization's more complex Fracture Risk Assessment Tool, according to an analysis of data from a prospective study of 6,252 older white women.

The results suggest that “the addition of [complex] clinical risk factor information to age and BMD alone does not enhance the prediction of these fractures in older women,” said Dr. Kristine E. Ensrud, professor of medicine at the University of Minnesota, Minneapolis.

The FRAX algorithm is designed to predict only the 10-year probability of a hip fracture or a major osteoporotic fracture. It builds a risk profile based on nine clinical risk factors (age, sex, prior history of fracture, oral glucocorticoid use, presence of rheumatoid arthritis, parental history of hip fracture, smoking status, alcohol consumption, and body mass index).

Dr. Ensrud and her colleagues used data from 6,252 participants in the Study of Osteoporotic Fractures, which enrolled women during 1986–1988. Hip BMD measurements and all of the FRAX clinical risk factors were available for these women, who had an average age of 71 years. Incident fractures were confirmed in 98% of cases reported during the study's 10-year follow-up period.

A combination of age and hip BMD had significantly greater ability to predict the 10-year risk of a hip fracture than did the FRAX algorithm alone, based on area-under-the-curve (AUC) statistics that the investigators calculated from receiver operating characteristic curves that were built with data from the study. However, the AUC statistic that was derived from the age-plus-hip-BMD model (0.76) was similar to that obtained with FRAX plus hip BMD (0.75). The AUC statistic for FRAX alone was 0.71. (An AUC of 0.50 reflects a predictive ability equal to chance.)

Similarly, age plus hip BMD had a significantly greater ability to predict both major osteoporotic fractures (hip, clinical spine, wrist, or humerus) and clinical fractures (defined as nonvertebral or clinical vertebral fractures) than did the FRAX algorithm alone, Dr. Ensrud reported at the annual meeting of the American Society for Bone and Mineral Research.

To refine their analysis further, Dr. Ensrud and her associates compared the proportion of women across the models who were classified in the highest decile of fracture risk and who actually experienced a fracture outcome. This type of assessment enhances the clinical usefulness of a risk prediction model because it contains a higher proportion of women who actually experienced the outcome in question, she said.

This simple model of age and prior fracture history (rather than hip BMD) also predicted the 10-year risk of hip, osteoporotic, and clinical fractures just as well as the FRAX algorithm alone did. This finding suggests that “in a setting where BMD is not available, the addition of [complex] clinical risk factor information to age and prior fracture history alone does not enhance the prediction of these fractures in older women,” Dr. Ensrud said.

The study was funded by the National Institute on Aging.

MONTREAL — A history of unresponsiveness to bisphosphonate therapies does not appear to diminish the bone-building effects of teriparatide in women with osteoporosis, judging from the findings of a small, uncontrolled, 18-month study.

The anabolic effects of teriparatide (Forteo), an injectable form of recombinant human parathyroid hormone, on bone mineral density (BMD) were apparent by 6 months into treatment and were accompanied by significant changes in biomarkers of bone turnover and positive changes in bone structure on MicroCT imaging, Dr. Burkhard Muche said at the annual meeting of the American Society for Bone and Mineral Research.

The results suggest that patients who are resistant to oral bisphosphonate therapy could use teriparatide in treatment cycles lasting at least 6 months, followed by an antiresorptive agent such as raloxifene (Evista), strontium ranelate, or an intravenous bisphosphonate, in order to optimize the beneficial effects of the anabolic agent, said Dr. Muche of the department of metabolic diseases/osteology at Immanuel-Krankenhaus, Berlin.

Of 25 women in the study with a mean age of 69 years, 14 had a new fragility fracture and 11 had a significant decline in BMD of greater than 3.5%, despite previous treatment with oral bisphosphonates lasting at least 12 months. Half had taken risedronate (Actonel) and half had taken alendronate (Fosamax) for a mean of 3.5 years (range of 1–7 years). The women also received 500 mg of calcium and 400 IU of vitamin D3 each day.

The investigators detected significant increases in BMD at the lumbar spine after 6, 12, and 18 months of teriparatide. By 18 months, the women had a mean 9% increase in BMD at the lumbar spine. No significant changes developed in the total BMD of the femoral neck or the hip.

Intermittent asymptomatic hypercalcemia occurred in four patients.

Levels of the bone formation marker bone alkaline phosphatase significantly increased from 15 ng/L at baseline to 28 ng/L at 6 months, but then decreased through 18 months. Concentrations of a marker of bone resorption, beta C-terminal telopeptide of type I collagen (α-CTX), followed the same trend.

Dr. Muche and his colleagues obtained paired bone biopsies from the dorsal iliac crest at baseline, from the opposite side at 6 months, and again from the original side at 18 months. Parameters of bone structure on MicroCT imaging increased early during the course of treatment.

Dr. Muche received a travel grant from Lilly Germany, which funded the study. Eli Lilly & Co. makes teriparatide.

MONTREAL — A history of unresponsiveness to bisphosphonate therapies does not appear to diminish the bone-building effects of teriparatide in women with osteoporosis, judging from the findings of a small, uncontrolled, 18-month study.

The anabolic effects of teriparatide (Forteo), an injectable form of recombinant human parathyroid hormone, on bone mineral density (BMD) were apparent by 6 months into treatment and were accompanied by significant changes in biomarkers of bone turnover and positive changes in bone structure on MicroCT imaging, Dr. Burkhard Muche said at the annual meeting of the American Society for Bone and Mineral Research.

The results suggest that patients who are resistant to oral bisphosphonate therapy could use teriparatide in treatment cycles lasting at least 6 months, followed by an antiresorptive agent such as raloxifene (Evista), strontium ranelate, or an intravenous bisphosphonate, in order to optimize the beneficial effects of the anabolic agent, said Dr. Muche of the department of metabolic diseases/osteology at Immanuel-Krankenhaus, Berlin.

Of 25 women in the study with a mean age of 69 years, 14 had a new fragility fracture and 11 had a significant decline in BMD of greater than 3.5%, despite previous treatment with oral bisphosphonates lasting at least 12 months. Half had taken risedronate (Actonel) and half had taken alendronate (Fosamax) for a mean of 3.5 years (range of 1–7 years). The women also received 500 mg of calcium and 400 IU of vitamin D3 each day.

The investigators detected significant increases in BMD at the lumbar spine after 6, 12, and 18 months of teriparatide. By 18 months, the women had a mean 9% increase in BMD at the lumbar spine. No significant changes developed in the total BMD of the femoral neck or the hip.

Intermittent asymptomatic hypercalcemia occurred in four patients.

Levels of the bone formation marker bone alkaline phosphatase significantly increased from 15 ng/L at baseline to 28 ng/L at 6 months, but then decreased through 18 months. Concentrations of a marker of bone resorption, beta C-terminal telopeptide of type I collagen (α-CTX), followed the same trend.

Dr. Muche and his colleagues obtained paired bone biopsies from the dorsal iliac crest at baseline, from the opposite side at 6 months, and again from the original side at 18 months. Parameters of bone structure on MicroCT imaging increased early during the course of treatment.

Dr. Muche received a travel grant from Lilly Germany, which funded the study. Eli Lilly & Co. makes teriparatide.

MONTREAL — A history of unresponsiveness to bisphosphonate therapies does not appear to diminish the bone-building effects of teriparatide in women with osteoporosis, judging from the findings of a small, uncontrolled, 18-month study.

The anabolic effects of teriparatide (Forteo), an injectable form of recombinant human parathyroid hormone, on bone mineral density (BMD) were apparent by 6 months into treatment and were accompanied by significant changes in biomarkers of bone turnover and positive changes in bone structure on MicroCT imaging, Dr. Burkhard Muche said at the annual meeting of the American Society for Bone and Mineral Research.

The results suggest that patients who are resistant to oral bisphosphonate therapy could use teriparatide in treatment cycles lasting at least 6 months, followed by an antiresorptive agent such as raloxifene (Evista), strontium ranelate, or an intravenous bisphosphonate, in order to optimize the beneficial effects of the anabolic agent, said Dr. Muche of the department of metabolic diseases/osteology at Immanuel-Krankenhaus, Berlin.

Of 25 women in the study with a mean age of 69 years, 14 had a new fragility fracture and 11 had a significant decline in BMD of greater than 3.5%, despite previous treatment with oral bisphosphonates lasting at least 12 months. Half had taken risedronate (Actonel) and half had taken alendronate (Fosamax) for a mean of 3.5 years (range of 1–7 years). The women also received 500 mg of calcium and 400 IU of vitamin D3 each day.

The investigators detected significant increases in BMD at the lumbar spine after 6, 12, and 18 months of teriparatide. By 18 months, the women had a mean 9% increase in BMD at the lumbar spine. No significant changes developed in the total BMD of the femoral neck or the hip.

Intermittent asymptomatic hypercalcemia occurred in four patients.

Levels of the bone formation marker bone alkaline phosphatase significantly increased from 15 ng/L at baseline to 28 ng/L at 6 months, but then decreased through 18 months. Concentrations of a marker of bone resorption, beta C-terminal telopeptide of type I collagen (α-CTX), followed the same trend.

Dr. Muche and his colleagues obtained paired bone biopsies from the dorsal iliac crest at baseline, from the opposite side at 6 months, and again from the original side at 18 months. Parameters of bone structure on MicroCT imaging increased early during the course of treatment.

Dr. Muche received a travel grant from Lilly Germany, which funded the study. Eli Lilly & Co. makes teriparatide.

SAN FRANCISCO — When it comes to alternative therapies for osteoporosis, data are sparse and most do not point to efficacy.

Speaking at the annual meeting of the International Society for Clinical Densitometry, Rogene Tesar, Ph.D., reported available data based on her review:

▸ Strontium. The form that is studied most of 20 supplement compounds is strontium ranelate, which consists of about 340 mg strontium in 1 g of compound.

The Food and Drug Administration is considering approval of strontium ranelate for the treatment of osteoporosis because in two large phase III studies it promoted bone formation, decreased resorption, and reduced fracture risk in postmenopausal women, said Dr. Tesar, who is in private practice in Austin, Texas. The Spinal Osteoporosis Therapeutic Intervention (SOTI) trial of 1,649 patients with a previous vertebral fracture found a 41% reduction in vertebral fracture risk after 3 years of taking strontium ranelate 2 g/day, compared with placebo. Bone mineral density (BMD) increased in the spine by 14% and in the hip by 8% in the strontium group, compared with placebo. The Treatment of Peripheral Osteoporosis (TROPOS) study of 5,091 patients with low hip BMD showed a 39% reduction in vertebral fractures and a 16% reduction in non-vertebral fractures, compared with placebo, over a 3-year period.

A related product, OsteoValin, has strontium carbonate as its main ingredient and is licensed in Europe as a prescription drug to treat osteoporosis. OsteoValin is available in the U.S. over the counter for around $27 for 30 capsules, Dr. Tesar said. Efficacy data, however, are based on only six patients and no control group. In addition, the product is not regulated well enough to ensure its quality and safety.

▸ Soy isoflavones. Although there is solid evidence for prevention of bone loss in animals given soy isoflavones, human data are mixed, Dr. Tesar said.

A double-blind, randomized, placebo-controlled study of 203 women within a decade of menopause reported in 2005 that high-dose isoflavones (80 mg) produced a mild but significant preservation of hip BMD over 1 year. A separate randomized, placebo-controlled study found that 2 years of soy milk with isoflavones prevented spine bone loss in postmenopausal women. The study concluded that two glasses of soy milk containing 76 mg isoflavones per day prevent lumbar spine bone loss.

▸ Vitamin K2. Positive evidence comes mainly from Japan, where a vitamin K2 compound called menatetrenone is standard treatment for osteopenia, Dr. Tesar said. A 2-year study of 241 osteoporotic women reported in 2000 that those taking 45 mg/day of a menatetrenone product called Gla-kay, plus calcium lactate, lost 1% of lumbar spine BMD, compared with a 3% loss in patients taking calcium supplements alone. A separate 2-year study of 172 postmenopausal women found a slight (0.1%) increase in lumbar spine density with vitamin K2 and a more marked (5%) increase with vitamin K2 plus vitamin D3.

▸ Tai Chi. A 1-year study of 34 postmenopausal women in 2002 found generalized bone loss in the 17 women who did 3.5 hours/week of tai chi and in the 17 who did not exercise, but the tai chi group had a lower rate of bone loss. A separate randomized study of 132 menopausal, sedentary women in 2004 also showed a lower rate of bone loss in those who practiced tai chi for 45 minutes a day, 5 days a week, compared with sedentary controls.

There is evidence for prevention of bone loss in animals given soy isoflavones, but human data are mixed. DR. TESAR

SAN FRANCISCO — When it comes to alternative therapies for osteoporosis, data are sparse and most do not point to efficacy.

Speaking at the annual meeting of the International Society for Clinical Densitometry, Rogene Tesar, Ph.D., reported available data based on her review:

▸ Strontium. The form that is studied most of 20 supplement compounds is strontium ranelate, which consists of about 340 mg strontium in 1 g of compound.

The Food and Drug Administration is considering approval of strontium ranelate for the treatment of osteoporosis because in two large phase III studies it promoted bone formation, decreased resorption, and reduced fracture risk in postmenopausal women, said Dr. Tesar, who is in private practice in Austin, Texas. The Spinal Osteoporosis Therapeutic Intervention (SOTI) trial of 1,649 patients with a previous vertebral fracture found a 41% reduction in vertebral fracture risk after 3 years of taking strontium ranelate 2 g/day, compared with placebo. Bone mineral density (BMD) increased in the spine by 14% and in the hip by 8% in the strontium group, compared with placebo. The Treatment of Peripheral Osteoporosis (TROPOS) study of 5,091 patients with low hip BMD showed a 39% reduction in vertebral fractures and a 16% reduction in non-vertebral fractures, compared with placebo, over a 3-year period.

A related product, OsteoValin, has strontium carbonate as its main ingredient and is licensed in Europe as a prescription drug to treat osteoporosis. OsteoValin is available in the U.S. over the counter for around $27 for 30 capsules, Dr. Tesar said. Efficacy data, however, are based on only six patients and no control group. In addition, the product is not regulated well enough to ensure its quality and safety.

▸ Soy isoflavones. Although there is solid evidence for prevention of bone loss in animals given soy isoflavones, human data are mixed, Dr. Tesar said.

A double-blind, randomized, placebo-controlled study of 203 women within a decade of menopause reported in 2005 that high-dose isoflavones (80 mg) produced a mild but significant preservation of hip BMD over 1 year. A separate randomized, placebo-controlled study found that 2 years of soy milk with isoflavones prevented spine bone loss in postmenopausal women. The study concluded that two glasses of soy milk containing 76 mg isoflavones per day prevent lumbar spine bone loss.

▸ Vitamin K2. Positive evidence comes mainly from Japan, where a vitamin K2 compound called menatetrenone is standard treatment for osteopenia, Dr. Tesar said. A 2-year study of 241 osteoporotic women reported in 2000 that those taking 45 mg/day of a menatetrenone product called Gla-kay, plus calcium lactate, lost 1% of lumbar spine BMD, compared with a 3% loss in patients taking calcium supplements alone. A separate 2-year study of 172 postmenopausal women found a slight (0.1%) increase in lumbar spine density with vitamin K2 and a more marked (5%) increase with vitamin K2 plus vitamin D3.

▸ Tai Chi. A 1-year study of 34 postmenopausal women in 2002 found generalized bone loss in the 17 women who did 3.5 hours/week of tai chi and in the 17 who did not exercise, but the tai chi group had a lower rate of bone loss. A separate randomized study of 132 menopausal, sedentary women in 2004 also showed a lower rate of bone loss in those who practiced tai chi for 45 minutes a day, 5 days a week, compared with sedentary controls.

There is evidence for prevention of bone loss in animals given soy isoflavones, but human data are mixed. DR. TESAR

SAN FRANCISCO — When it comes to alternative therapies for osteoporosis, data are sparse and most do not point to efficacy.

Speaking at the annual meeting of the International Society for Clinical Densitometry, Rogene Tesar, Ph.D., reported available data based on her review:

▸ Strontium. The form that is studied most of 20 supplement compounds is strontium ranelate, which consists of about 340 mg strontium in 1 g of compound.

The Food and Drug Administration is considering approval of strontium ranelate for the treatment of osteoporosis because in two large phase III studies it promoted bone formation, decreased resorption, and reduced fracture risk in postmenopausal women, said Dr. Tesar, who is in private practice in Austin, Texas. The Spinal Osteoporosis Therapeutic Intervention (SOTI) trial of 1,649 patients with a previous vertebral fracture found a 41% reduction in vertebral fracture risk after 3 years of taking strontium ranelate 2 g/day, compared with placebo. Bone mineral density (BMD) increased in the spine by 14% and in the hip by 8% in the strontium group, compared with placebo. The Treatment of Peripheral Osteoporosis (TROPOS) study of 5,091 patients with low hip BMD showed a 39% reduction in vertebral fractures and a 16% reduction in non-vertebral fractures, compared with placebo, over a 3-year period.

A related product, OsteoValin, has strontium carbonate as its main ingredient and is licensed in Europe as a prescription drug to treat osteoporosis. OsteoValin is available in the U.S. over the counter for around $27 for 30 capsules, Dr. Tesar said. Efficacy data, however, are based on only six patients and no control group. In addition, the product is not regulated well enough to ensure its quality and safety.

▸ Soy isoflavones. Although there is solid evidence for prevention of bone loss in animals given soy isoflavones, human data are mixed, Dr. Tesar said.

A double-blind, randomized, placebo-controlled study of 203 women within a decade of menopause reported in 2005 that high-dose isoflavones (80 mg) produced a mild but significant preservation of hip BMD over 1 year. A separate randomized, placebo-controlled study found that 2 years of soy milk with isoflavones prevented spine bone loss in postmenopausal women. The study concluded that two glasses of soy milk containing 76 mg isoflavones per day prevent lumbar spine bone loss.

▸ Vitamin K2. Positive evidence comes mainly from Japan, where a vitamin K2 compound called menatetrenone is standard treatment for osteopenia, Dr. Tesar said. A 2-year study of 241 osteoporotic women reported in 2000 that those taking 45 mg/day of a menatetrenone product called Gla-kay, plus calcium lactate, lost 1% of lumbar spine BMD, compared with a 3% loss in patients taking calcium supplements alone. A separate 2-year study of 172 postmenopausal women found a slight (0.1%) increase in lumbar spine density with vitamin K2 and a more marked (5%) increase with vitamin K2 plus vitamin D3.

▸ Tai Chi. A 1-year study of 34 postmenopausal women in 2002 found generalized bone loss in the 17 women who did 3.5 hours/week of tai chi and in the 17 who did not exercise, but the tai chi group had a lower rate of bone loss. A separate randomized study of 132 menopausal, sedentary women in 2004 also showed a lower rate of bone loss in those who practiced tai chi for 45 minutes a day, 5 days a week, compared with sedentary controls.

There is evidence for prevention of bone loss in animals given soy isoflavones, but human data are mixed. DR. TESAR

MONTREAL — Consumption of vitamin C at sufficiently high levels is associated with nearly a 50% decrease in the risk of hip and nonvertebral osteoporotic fractures in elderly men and women, according to a 15- to 17-year follow-up of patients in the Framingham Osteoporosis Study.

Previous studies of menopausal and postmenopausal women have shown that dietary intake of vitamin C is associated with increased bone mineral density (BMD), and that a high vitamin C serum level is associated with a decreased prevalence of fracture. Poor dietary intake of vitamin C also has been associated with an increased risk of hip fracture, Marian T. Hannan, D.Sc., said at the annual meeting of the American Society for Bone and Mineral Research.

Vitamin C, an antioxidant, plays an important role in the formation of collagen, which is a major component of connective tissue. Published evidence suggests that oxidative stress may result in increased osteoclast formation, resulting in greater bone resorption, said Dr. Hannan, who presented the study on behalf of Shivani Sahni of Tufts University, Boston. (Ms. Sahni performed the research as a part of her thesis but could not attend the meeting.)

Of 5,209 men and women in the original Framingham Heart Study cohort, the investigators identified 958 individuals who had participated in the beginning of the osteoporosis study in 1988–1989, had answered a food-frequency questionnaire, and had no history of a hip fracture. These individuals had a mean age of 75 years and experienced 100 hip fractures and 180 nonvertebral osteoporotic fractures during the follow-up period, Dr. Hannan reported.

For the study, participants were divided into three groups based on their intake of vitamin C. The relative risk of hip fracture was significantly lower for individuals who had the highest total intake of both dietary and supplemental vitamin C (a median of 305 mg/day) than it was for people with the lowest total intake (median of 97 mg/day). This translated into a 44% decrease in relative risk of hip fracture, according to Dr. Hannan of Harvard Medical School's Institute for Aging Research, Boston.

Those with the highest total intake of vitamin C also had a 36% lower relative risk of having a nonvertebral osteoporotic fracture than did individuals with the lowest total intake.

When the investigators looked at supplemental vitamin C intake alone, the highest users (median of 260 mg/day) had a 70% lower relative risk of hip fracture than did nonusers. Supplements accounted for about 28% of the individuals' total vitamin C intake, Dr. Hannan said.

The investigators found no effect for dietary intake of vitamin C alone.

All of the comparisons were adjusted for age, sex, body mass index, height, smoking status, estrogen use in women, physical activity, alcohol use, multivitamin use, femoral neck BMD, and total intake of energy, calcium, vitamin D, and potassium.

One audience member suggested that the discrepancy between the effects of supplemental and dietary vitamin C intake could mean that there are residual confounding effects from factors that were not accounted for in the study, such that supplemental use of vitamin C may be a marker for people who care more about their health and take better care of themselves. This is a problem that can only be answered with a randomized, controlled trial, Dr. Hannan noted.

“We were intrigued by the lack of a BMD effect on [the association between] vitamin C and fracture, and we believe that it implies that vitamin C may affect a different pathway or other fracture risk factors, for example, fall risk factors or mobility risk factors,” Dr. Hannan said.

Future research should investigate “alternative mechanisms for vitamin C that are independent of BMD … [and] evaluate whether an increase in the recommended dietary intake for vitamin C should take into account the preventive effects seen in this study” and in other types of studies, as well as the protective effects that vitamin C has in other chronic diseases.

MONTREAL — Consumption of vitamin C at sufficiently high levels is associated with nearly a 50% decrease in the risk of hip and nonvertebral osteoporotic fractures in elderly men and women, according to a 15- to 17-year follow-up of patients in the Framingham Osteoporosis Study.

Previous studies of menopausal and postmenopausal women have shown that dietary intake of vitamin C is associated with increased bone mineral density (BMD), and that a high vitamin C serum level is associated with a decreased prevalence of fracture. Poor dietary intake of vitamin C also has been associated with an increased risk of hip fracture, Marian T. Hannan, D.Sc., said at the annual meeting of the American Society for Bone and Mineral Research.

Vitamin C, an antioxidant, plays an important role in the formation of collagen, which is a major component of connective tissue. Published evidence suggests that oxidative stress may result in increased osteoclast formation, resulting in greater bone resorption, said Dr. Hannan, who presented the study on behalf of Shivani Sahni of Tufts University, Boston. (Ms. Sahni performed the research as a part of her thesis but could not attend the meeting.)

Of 5,209 men and women in the original Framingham Heart Study cohort, the investigators identified 958 individuals who had participated in the beginning of the osteoporosis study in 1988–1989, had answered a food-frequency questionnaire, and had no history of a hip fracture. These individuals had a mean age of 75 years and experienced 100 hip fractures and 180 nonvertebral osteoporotic fractures during the follow-up period, Dr. Hannan reported.

For the study, participants were divided into three groups based on their intake of vitamin C. The relative risk of hip fracture was significantly lower for individuals who had the highest total intake of both dietary and supplemental vitamin C (a median of 305 mg/day) than it was for people with the lowest total intake (median of 97 mg/day). This translated into a 44% decrease in relative risk of hip fracture, according to Dr. Hannan of Harvard Medical School's Institute for Aging Research, Boston.

Those with the highest total intake of vitamin C also had a 36% lower relative risk of having a nonvertebral osteoporotic fracture than did individuals with the lowest total intake.

When the investigators looked at supplemental vitamin C intake alone, the highest users (median of 260 mg/day) had a 70% lower relative risk of hip fracture than did nonusers. Supplements accounted for about 28% of the individuals' total vitamin C intake, Dr. Hannan said.

The investigators found no effect for dietary intake of vitamin C alone.

All of the comparisons were adjusted for age, sex, body mass index, height, smoking status, estrogen use in women, physical activity, alcohol use, multivitamin use, femoral neck BMD, and total intake of energy, calcium, vitamin D, and potassium.

One audience member suggested that the discrepancy between the effects of supplemental and dietary vitamin C intake could mean that there are residual confounding effects from factors that were not accounted for in the study, such that supplemental use of vitamin C may be a marker for people who care more about their health and take better care of themselves. This is a problem that can only be answered with a randomized, controlled trial, Dr. Hannan noted.

“We were intrigued by the lack of a BMD effect on [the association between] vitamin C and fracture, and we believe that it implies that vitamin C may affect a different pathway or other fracture risk factors, for example, fall risk factors or mobility risk factors,” Dr. Hannan said.

Future research should investigate “alternative mechanisms for vitamin C that are independent of BMD … [and] evaluate whether an increase in the recommended dietary intake for vitamin C should take into account the preventive effects seen in this study” and in other types of studies, as well as the protective effects that vitamin C has in other chronic diseases.

MONTREAL — Consumption of vitamin C at sufficiently high levels is associated with nearly a 50% decrease in the risk of hip and nonvertebral osteoporotic fractures in elderly men and women, according to a 15- to 17-year follow-up of patients in the Framingham Osteoporosis Study.

Previous studies of menopausal and postmenopausal women have shown that dietary intake of vitamin C is associated with increased bone mineral density (BMD), and that a high vitamin C serum level is associated with a decreased prevalence of fracture. Poor dietary intake of vitamin C also has been associated with an increased risk of hip fracture, Marian T. Hannan, D.Sc., said at the annual meeting of the American Society for Bone and Mineral Research.

Vitamin C, an antioxidant, plays an important role in the formation of collagen, which is a major component of connective tissue. Published evidence suggests that oxidative stress may result in increased osteoclast formation, resulting in greater bone resorption, said Dr. Hannan, who presented the study on behalf of Shivani Sahni of Tufts University, Boston. (Ms. Sahni performed the research as a part of her thesis but could not attend the meeting.)

Of 5,209 men and women in the original Framingham Heart Study cohort, the investigators identified 958 individuals who had participated in the beginning of the osteoporosis study in 1988–1989, had answered a food-frequency questionnaire, and had no history of a hip fracture. These individuals had a mean age of 75 years and experienced 100 hip fractures and 180 nonvertebral osteoporotic fractures during the follow-up period, Dr. Hannan reported.

For the study, participants were divided into three groups based on their intake of vitamin C. The relative risk of hip fracture was significantly lower for individuals who had the highest total intake of both dietary and supplemental vitamin C (a median of 305 mg/day) than it was for people with the lowest total intake (median of 97 mg/day). This translated into a 44% decrease in relative risk of hip fracture, according to Dr. Hannan of Harvard Medical School's Institute for Aging Research, Boston.

Those with the highest total intake of vitamin C also had a 36% lower relative risk of having a nonvertebral osteoporotic fracture than did individuals with the lowest total intake.

When the investigators looked at supplemental vitamin C intake alone, the highest users (median of 260 mg/day) had a 70% lower relative risk of hip fracture than did nonusers. Supplements accounted for about 28% of the individuals' total vitamin C intake, Dr. Hannan said.

The investigators found no effect for dietary intake of vitamin C alone.

All of the comparisons were adjusted for age, sex, body mass index, height, smoking status, estrogen use in women, physical activity, alcohol use, multivitamin use, femoral neck BMD, and total intake of energy, calcium, vitamin D, and potassium.

One audience member suggested that the discrepancy between the effects of supplemental and dietary vitamin C intake could mean that there are residual confounding effects from factors that were not accounted for in the study, such that supplemental use of vitamin C may be a marker for people who care more about their health and take better care of themselves. This is a problem that can only be answered with a randomized, controlled trial, Dr. Hannan noted.

“We were intrigued by the lack of a BMD effect on [the association between] vitamin C and fracture, and we believe that it implies that vitamin C may affect a different pathway or other fracture risk factors, for example, fall risk factors or mobility risk factors,” Dr. Hannan said.

Future research should investigate “alternative mechanisms for vitamin C that are independent of BMD … [and] evaluate whether an increase in the recommended dietary intake for vitamin C should take into account the preventive effects seen in this study” and in other types of studies, as well as the protective effects that vitamin C has in other chronic diseases.