Mitchel L. Zoler, PhD

Treatment for 6 weeks with teriparatide, a U.S.-approved drug that stimulates bone remodeling, led to significant, 1-year improvements in alveolar bone formation and clinical outcomes in a controlled, pilot study of 40 patients undergoing periodontal surgery.

Bone gain in the osseous defects of the 20 patients who were randomized to receive daily teriparatide injections became detectable early after treatment began and continued to improve during 12 months of follow-up, leading to a highly significant improvement in overall alveolar bone gain, compared with the 20 patients on placebo, Jill D. Bashutski, D.D.S., and her associates reported (N. Engl. J. Med. 2010 Oct. 16 [doi:10.1056/NEJMoa1005361]).

The teriparatide-treated patients also had significantly better 1-year improvements in periodontal probing depth and clinical attachment, reported Dr. Bashutski, a periodontist at the University of Michigan in Ann Arbor. The article's online publication was timed to coincide with Dr. Bashutski's presentation of the findings at the annual meeting of the American Society for Bone and Mineral Research in Toronto.

She and her associates used teriparatide, a recombinant agent that contains the first 34 amino acids of parathyroid hormone, because of its activity as an anabolic agent and prior evidence that it enhances bone remodeling and wound healing in areas of high bone turnover, such as fractures and surgical sites.

“We know that parathyroid hormone stimulates formation of preosteoblast cells, and these cells go on to eventually form bone.” The 6-week regimen of daily teriparatide injections produces “an initial incentive for bone formation to occur” during subsequent months, said Dr. Laurie K. McCauley, the principal investigator of the study and professor and chair of periodontics and oral medicine at the University of Michigan, in an interview.

The positive effects that teriparatide treatment had on the study outcomes of bone gain, probing depth, and clinical attachment were also all clinically significant, Dr. McCauley added. Teriparatide increased 1-year bone gain at a rate that was 10-fold higher than placebo. “That's huge,” she said.

The long-term sequence of events that teriparatide triggers likely explains how a 6-week course produced significant differences after 1 year, she said. “We know that most connective tissue healing goes on during the first 6 weeks. The thought was to augment that healing with this agent.”

The outcome from “this small trial provides preliminary evidence that an agent that stimulates bone formation might confer additional benefit over that achieved with standard care in patients with periodontitis,” commented Dr. Andrew Grey in an editorial that accompanied the article (N. Engl. J. Med. 2010 Oct. 16 [doi:10.1056/NEJMe1010459]). But many questions about this treatment remain, he said. “How durable is the effect of teriparatide? What is the optimal dosing regimen? Does teriparatide alter important [end points] such as tooth loss or the need for further operative intervention? Do antiresorptive agents, which cost considerably less than teriparatide, confer similar benefits?” asked Dr. Grey, an endocrinologist at the University of Auckland (New Zealand).

The study enrolled patients (aged 30-65 years) with severe periodontal disease at the University of Michigan from January 2005 to June 2009. All patients had normal levels of calcium and parathyroid hormone, a minimum vitamin D level of 16 ng/mL, and no osteoporosis. All patients underwent conventional surgery on an osseous defect. Starting 3 days before surgery, patients began daily treatment with either 20 mcg teriparatide or placebo, administered daily by subcutaneous injection, for 6 weeks. All patients also received a daily supplement of calcium and vitamin D.

Patients who were treated with teriparatide had significantly better resolution of their periodontal bone defects at 6, 9, and 12 months following baseline, compared with the placebo patients. At 12 months, the teriparatide-treated patients averaged a bone gain of 1.86 mm (29%), compared with baseline, whereas the placebo patients averaged a 0.16-mm (3%) gain from baseline.

Teriparatide treatment was also linked with a 2.42-mm (33%) average reduction in probing depth at the surgical site after 12 months, compared with baseline. The placebo group averaged a 1.32-mm (20%) reduction in probing depth from baseline, a statistically significant difference. Clinical attachment improved by 1.58 mm (22%) at 1 year, compared with baseline, in the teriparatide patients, significantly better than the 0.42-mm (7%) average attachment improvement in the placebo group. No improvements in probing depth occurred in the teriparatide and placebo patients in areas of severe, chronic periodontitis that did not undergo surgery.

At entry to the study, five patients in the teriparatide arm and nine in the placebo group had osteopenia on dual-energy x-ray absorptiometry examinations. At the 12-month follow-up, patients in both study arms showed no significant changes in bone density scores or in quality of life scores. Teriparatide treatment did not link with any pattern of adverse events that differed from the placebo group.

Although teriparatide is available for treating osteoporosis, its widespread use in patients who are undergoing periodontal surgery should await results from studies involving larger numbers of patients, Dr. McCauley said. She also cautioned against extrapolating the results to other types of bone surgery. Dr. McCauley said she would like to run studies on a delayed-release, topical formulation of teriparatide that would be implanted during surgery and would then release over the subsequent 6 weeks, precluding daily injections. Formulations of this type now exist, but have not reached the clinical-testing stage.

The study received partial funding from Eli Lilly & Co., the company that markets teriparatide (Forteo), but it was an investigator-initiated study. Dr. McCauley has received research grants and transportation support from Lilly. She has also received research grants and has been a consultant to Amgen Inc., but she has not received any honoraria or consulting fees. Dr. Bashutski said she has received travel expenses from the Colgate-Palmolive Co. Dr. Grey said that he has received travel expenses from Merck Sharp & Dohme (NZ) Ltd.

Improvements in periodontal probing depth and clinical attachment were significant.

Source DR. BASHUTSKI

Teriparatide increased 1-year bone gain at a rate that was 10-fold higher than placebo. 'That's huge.'

Source DR. McCAULEY

Treatment for 6 weeks with teriparatide, a U.S.-approved drug that stimulates bone remodeling, led to significant, 1-year improvements in alveolar bone formation and clinical outcomes in a controlled, pilot study of 40 patients undergoing periodontal surgery.

Bone gain in the osseous defects of the 20 patients who were randomized to receive daily teriparatide injections became detectable early after treatment began and continued to improve during 12 months of follow-up, leading to a highly significant improvement in overall alveolar bone gain, compared with the 20 patients on placebo, Jill D. Bashutski, D.D.S., and her associates reported (N. Engl. J. Med. 2010 Oct. 16 [doi:10.1056/NEJMoa1005361]).

The teriparatide-treated patients also had significantly better 1-year improvements in periodontal probing depth and clinical attachment, reported Dr. Bashutski, a periodontist at the University of Michigan in Ann Arbor. The article's online publication was timed to coincide with Dr. Bashutski's presentation of the findings at the annual meeting of the American Society for Bone and Mineral Research in Toronto.

She and her associates used teriparatide, a recombinant agent that contains the first 34 amino acids of parathyroid hormone, because of its activity as an anabolic agent and prior evidence that it enhances bone remodeling and wound healing in areas of high bone turnover, such as fractures and surgical sites.

“We know that parathyroid hormone stimulates formation of preosteoblast cells, and these cells go on to eventually form bone.” The 6-week regimen of daily teriparatide injections produces “an initial incentive for bone formation to occur” during subsequent months, said Dr. Laurie K. McCauley, the principal investigator of the study and professor and chair of periodontics and oral medicine at the University of Michigan, in an interview.

The positive effects that teriparatide treatment had on the study outcomes of bone gain, probing depth, and clinical attachment were also all clinically significant, Dr. McCauley added. Teriparatide increased 1-year bone gain at a rate that was 10-fold higher than placebo. “That's huge,” she said.

The long-term sequence of events that teriparatide triggers likely explains how a 6-week course produced significant differences after 1 year, she said. “We know that most connective tissue healing goes on during the first 6 weeks. The thought was to augment that healing with this agent.”

The outcome from “this small trial provides preliminary evidence that an agent that stimulates bone formation might confer additional benefit over that achieved with standard care in patients with periodontitis,” commented Dr. Andrew Grey in an editorial that accompanied the article (N. Engl. J. Med. 2010 Oct. 16 [doi:10.1056/NEJMe1010459]). But many questions about this treatment remain, he said. “How durable is the effect of teriparatide? What is the optimal dosing regimen? Does teriparatide alter important [end points] such as tooth loss or the need for further operative intervention? Do antiresorptive agents, which cost considerably less than teriparatide, confer similar benefits?” asked Dr. Grey, an endocrinologist at the University of Auckland (New Zealand).

The study enrolled patients (aged 30-65 years) with severe periodontal disease at the University of Michigan from January 2005 to June 2009. All patients had normal levels of calcium and parathyroid hormone, a minimum vitamin D level of 16 ng/mL, and no osteoporosis. All patients underwent conventional surgery on an osseous defect. Starting 3 days before surgery, patients began daily treatment with either 20 mcg teriparatide or placebo, administered daily by subcutaneous injection, for 6 weeks. All patients also received a daily supplement of calcium and vitamin D.

Patients who were treated with teriparatide had significantly better resolution of their periodontal bone defects at 6, 9, and 12 months following baseline, compared with the placebo patients. At 12 months, the teriparatide-treated patients averaged a bone gain of 1.86 mm (29%), compared with baseline, whereas the placebo patients averaged a 0.16-mm (3%) gain from baseline.

Teriparatide treatment was also linked with a 2.42-mm (33%) average reduction in probing depth at the surgical site after 12 months, compared with baseline. The placebo group averaged a 1.32-mm (20%) reduction in probing depth from baseline, a statistically significant difference. Clinical attachment improved by 1.58 mm (22%) at 1 year, compared with baseline, in the teriparatide patients, significantly better than the 0.42-mm (7%) average attachment improvement in the placebo group. No improvements in probing depth occurred in the teriparatide and placebo patients in areas of severe, chronic periodontitis that did not undergo surgery.

At entry to the study, five patients in the teriparatide arm and nine in the placebo group had osteopenia on dual-energy x-ray absorptiometry examinations. At the 12-month follow-up, patients in both study arms showed no significant changes in bone density scores or in quality of life scores. Teriparatide treatment did not link with any pattern of adverse events that differed from the placebo group.

Although teriparatide is available for treating osteoporosis, its widespread use in patients who are undergoing periodontal surgery should await results from studies involving larger numbers of patients, Dr. McCauley said. She also cautioned against extrapolating the results to other types of bone surgery. Dr. McCauley said she would like to run studies on a delayed-release, topical formulation of teriparatide that would be implanted during surgery and would then release over the subsequent 6 weeks, precluding daily injections. Formulations of this type now exist, but have not reached the clinical-testing stage.

The study received partial funding from Eli Lilly & Co., the company that markets teriparatide (Forteo), but it was an investigator-initiated study. Dr. McCauley has received research grants and transportation support from Lilly. She has also received research grants and has been a consultant to Amgen Inc., but she has not received any honoraria or consulting fees. Dr. Bashutski said she has received travel expenses from the Colgate-Palmolive Co. Dr. Grey said that he has received travel expenses from Merck Sharp & Dohme (NZ) Ltd.

Improvements in periodontal probing depth and clinical attachment were significant.

Source DR. BASHUTSKI

Teriparatide increased 1-year bone gain at a rate that was 10-fold higher than placebo. 'That's huge.'

Source DR. McCAULEY

Treatment for 6 weeks with teriparatide, a U.S.-approved drug that stimulates bone remodeling, led to significant, 1-year improvements in alveolar bone formation and clinical outcomes in a controlled, pilot study of 40 patients undergoing periodontal surgery.

Bone gain in the osseous defects of the 20 patients who were randomized to receive daily teriparatide injections became detectable early after treatment began and continued to improve during 12 months of follow-up, leading to a highly significant improvement in overall alveolar bone gain, compared with the 20 patients on placebo, Jill D. Bashutski, D.D.S., and her associates reported (N. Engl. J. Med. 2010 Oct. 16 [doi:10.1056/NEJMoa1005361]).

The teriparatide-treated patients also had significantly better 1-year improvements in periodontal probing depth and clinical attachment, reported Dr. Bashutski, a periodontist at the University of Michigan in Ann Arbor. The article's online publication was timed to coincide with Dr. Bashutski's presentation of the findings at the annual meeting of the American Society for Bone and Mineral Research in Toronto.

She and her associates used teriparatide, a recombinant agent that contains the first 34 amino acids of parathyroid hormone, because of its activity as an anabolic agent and prior evidence that it enhances bone remodeling and wound healing in areas of high bone turnover, such as fractures and surgical sites.

“We know that parathyroid hormone stimulates formation of preosteoblast cells, and these cells go on to eventually form bone.” The 6-week regimen of daily teriparatide injections produces “an initial incentive for bone formation to occur” during subsequent months, said Dr. Laurie K. McCauley, the principal investigator of the study and professor and chair of periodontics and oral medicine at the University of Michigan, in an interview.

The positive effects that teriparatide treatment had on the study outcomes of bone gain, probing depth, and clinical attachment were also all clinically significant, Dr. McCauley added. Teriparatide increased 1-year bone gain at a rate that was 10-fold higher than placebo. “That's huge,” she said.

The long-term sequence of events that teriparatide triggers likely explains how a 6-week course produced significant differences after 1 year, she said. “We know that most connective tissue healing goes on during the first 6 weeks. The thought was to augment that healing with this agent.”

The outcome from “this small trial provides preliminary evidence that an agent that stimulates bone formation might confer additional benefit over that achieved with standard care in patients with periodontitis,” commented Dr. Andrew Grey in an editorial that accompanied the article (N. Engl. J. Med. 2010 Oct. 16 [doi:10.1056/NEJMe1010459]). But many questions about this treatment remain, he said. “How durable is the effect of teriparatide? What is the optimal dosing regimen? Does teriparatide alter important [end points] such as tooth loss or the need for further operative intervention? Do antiresorptive agents, which cost considerably less than teriparatide, confer similar benefits?” asked Dr. Grey, an endocrinologist at the University of Auckland (New Zealand).

The study enrolled patients (aged 30-65 years) with severe periodontal disease at the University of Michigan from January 2005 to June 2009. All patients had normal levels of calcium and parathyroid hormone, a minimum vitamin D level of 16 ng/mL, and no osteoporosis. All patients underwent conventional surgery on an osseous defect. Starting 3 days before surgery, patients began daily treatment with either 20 mcg teriparatide or placebo, administered daily by subcutaneous injection, for 6 weeks. All patients also received a daily supplement of calcium and vitamin D.

Patients who were treated with teriparatide had significantly better resolution of their periodontal bone defects at 6, 9, and 12 months following baseline, compared with the placebo patients. At 12 months, the teriparatide-treated patients averaged a bone gain of 1.86 mm (29%), compared with baseline, whereas the placebo patients averaged a 0.16-mm (3%) gain from baseline.

Teriparatide treatment was also linked with a 2.42-mm (33%) average reduction in probing depth at the surgical site after 12 months, compared with baseline. The placebo group averaged a 1.32-mm (20%) reduction in probing depth from baseline, a statistically significant difference. Clinical attachment improved by 1.58 mm (22%) at 1 year, compared with baseline, in the teriparatide patients, significantly better than the 0.42-mm (7%) average attachment improvement in the placebo group. No improvements in probing depth occurred in the teriparatide and placebo patients in areas of severe, chronic periodontitis that did not undergo surgery.

At entry to the study, five patients in the teriparatide arm and nine in the placebo group had osteopenia on dual-energy x-ray absorptiometry examinations. At the 12-month follow-up, patients in both study arms showed no significant changes in bone density scores or in quality of life scores. Teriparatide treatment did not link with any pattern of adverse events that differed from the placebo group.

Although teriparatide is available for treating osteoporosis, its widespread use in patients who are undergoing periodontal surgery should await results from studies involving larger numbers of patients, Dr. McCauley said. She also cautioned against extrapolating the results to other types of bone surgery. Dr. McCauley said she would like to run studies on a delayed-release, topical formulation of teriparatide that would be implanted during surgery and would then release over the subsequent 6 weeks, precluding daily injections. Formulations of this type now exist, but have not reached the clinical-testing stage.

The study received partial funding from Eli Lilly & Co., the company that markets teriparatide (Forteo), but it was an investigator-initiated study. Dr. McCauley has received research grants and transportation support from Lilly. She has also received research grants and has been a consultant to Amgen Inc., but she has not received any honoraria or consulting fees. Dr. Bashutski said she has received travel expenses from the Colgate-Palmolive Co. Dr. Grey said that he has received travel expenses from Merck Sharp & Dohme (NZ) Ltd.

Improvements in periodontal probing depth and clinical attachment were significant.

Source DR. BASHUTSKI

Teriparatide increased 1-year bone gain at a rate that was 10-fold higher than placebo. 'That's huge.'

Source DR. McCAULEY

TORONTO – The stronger a patient's bones are when bisphosphonate treatment is stopped, the less likely the bones are to fracture later, based on an analysis of 437 patients.

In contrast, changes in bone mineral density following the end of bisphosphonate therapy had no significant link with subsequent fracture risk, Dr. Douglas C. Bauer said at the meeting.

The finding calls into doubt the common practice of running annual dual-energy x-ray absorptiometry examinations on patients who have withdrawn from bisphosphonate treatment.

Routine BMD measurement “1-2 years after stopping prolonged alendronate therapy may not be useful for predicting the patient's fracture risk,” said Dr. Bauer, professor of medicine, epidemiology, and biostatistics at the University of California, San Francisco. The BMD at the time of alendronate discontinuation “was highly predictive of who was going to fracture.”

Patients who stopped alendronate therapy with a total hip BMD T score of −1.4 or greater had a 9% rate of clinical fracture during 5 years of follow-up. Patients with a T score of −2.1 to −1.5 when they stopped bisphosphonate treatment had a 23% fracture rate during 5 years of follow-up, and those who stopped with a T score lower than −2.1 had a 33% fracture rate over the next 5 years. The between-group differences were statistically significant.

These data “are helpful as I try to decide which of my patients I should leave on a bisphosphonate,” commented Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York. “Patients below −2.1 were at very high risk of fracture, but even those in the middle tertile, with less than −1.5, were at a risk almost as high.” Dr. Bauer's data “provides me with some comfort [on whom] I can stop safely.”

Dr. Bauer and his associates used data collected in the FLEX (Fracture Intervention Trial Long-Term Extension) study, which randomized 1,099 postmenopausal women who had completed 5 years of alendronate treatment to either continue on alendronate for another 5 years or switch to placebo (JAMA 2006;296:2927-38). They focused on the 437 patients who switched to placebo, and assessed the BMD measures that were associated with fracture risk during follow-up.

Even among patients who had relatively substantial bone loss during 1 year of follow-up, the amount of lost BMD did not significantly correlate with their follow-up fracture rate. The researchers saw no significant link to fracture rate among the 21% of patients who lost at least 3% of their BMD during the first year of follow-up, or among the 8% of patients who lost at least 5% of their BMD during 1 year of follow-up.

When a patient starts bisphosphonate treatment, the BMD typically rises sharply for a couple of years, and then plateaus and remains stable, Dr. Bauer said. After patients stop bisphosphonate treatment, their BMD usually declines gradually. Prior analysis of the FLEX data showed that patients who failed to reach a BMD of at least −2.5 usually benefited with fewer fractures when they remained on treatment. The new findings suggest that patients with T scores of less than −1.5 may also benefit from continued treatment. However, when patients reach an adequate BMD (greater than −1.5), “it's not unreasonable to talk with the patient about the potential risks and benefits of a drug holiday,” Dr. Bauer said.

The FLEX study was funded by Merck, which markets alendronate (Fosamax). Dr. Bauer has received research funding from Amgen, Merck, and Novartis.

BMD at the time of alendronate discontinuation 'was highly predictive of who was going to fracture.'

Source DR. BAUER

TORONTO – The stronger a patient's bones are when bisphosphonate treatment is stopped, the less likely the bones are to fracture later, based on an analysis of 437 patients.

In contrast, changes in bone mineral density following the end of bisphosphonate therapy had no significant link with subsequent fracture risk, Dr. Douglas C. Bauer said at the meeting.

The finding calls into doubt the common practice of running annual dual-energy x-ray absorptiometry examinations on patients who have withdrawn from bisphosphonate treatment.

Routine BMD measurement “1-2 years after stopping prolonged alendronate therapy may not be useful for predicting the patient's fracture risk,” said Dr. Bauer, professor of medicine, epidemiology, and biostatistics at the University of California, San Francisco. The BMD at the time of alendronate discontinuation “was highly predictive of who was going to fracture.”

Patients who stopped alendronate therapy with a total hip BMD T score of −1.4 or greater had a 9% rate of clinical fracture during 5 years of follow-up. Patients with a T score of −2.1 to −1.5 when they stopped bisphosphonate treatment had a 23% fracture rate during 5 years of follow-up, and those who stopped with a T score lower than −2.1 had a 33% fracture rate over the next 5 years. The between-group differences were statistically significant.

These data “are helpful as I try to decide which of my patients I should leave on a bisphosphonate,” commented Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York. “Patients below −2.1 were at very high risk of fracture, but even those in the middle tertile, with less than −1.5, were at a risk almost as high.” Dr. Bauer's data “provides me with some comfort [on whom] I can stop safely.”

Dr. Bauer and his associates used data collected in the FLEX (Fracture Intervention Trial Long-Term Extension) study, which randomized 1,099 postmenopausal women who had completed 5 years of alendronate treatment to either continue on alendronate for another 5 years or switch to placebo (JAMA 2006;296:2927-38). They focused on the 437 patients who switched to placebo, and assessed the BMD measures that were associated with fracture risk during follow-up.

Even among patients who had relatively substantial bone loss during 1 year of follow-up, the amount of lost BMD did not significantly correlate with their follow-up fracture rate. The researchers saw no significant link to fracture rate among the 21% of patients who lost at least 3% of their BMD during the first year of follow-up, or among the 8% of patients who lost at least 5% of their BMD during 1 year of follow-up.

When a patient starts bisphosphonate treatment, the BMD typically rises sharply for a couple of years, and then plateaus and remains stable, Dr. Bauer said. After patients stop bisphosphonate treatment, their BMD usually declines gradually. Prior analysis of the FLEX data showed that patients who failed to reach a BMD of at least −2.5 usually benefited with fewer fractures when they remained on treatment. The new findings suggest that patients with T scores of less than −1.5 may also benefit from continued treatment. However, when patients reach an adequate BMD (greater than −1.5), “it's not unreasonable to talk with the patient about the potential risks and benefits of a drug holiday,” Dr. Bauer said.

The FLEX study was funded by Merck, which markets alendronate (Fosamax). Dr. Bauer has received research funding from Amgen, Merck, and Novartis.

BMD at the time of alendronate discontinuation 'was highly predictive of who was going to fracture.'

Source DR. BAUER

TORONTO – The stronger a patient's bones are when bisphosphonate treatment is stopped, the less likely the bones are to fracture later, based on an analysis of 437 patients.

In contrast, changes in bone mineral density following the end of bisphosphonate therapy had no significant link with subsequent fracture risk, Dr. Douglas C. Bauer said at the meeting.

The finding calls into doubt the common practice of running annual dual-energy x-ray absorptiometry examinations on patients who have withdrawn from bisphosphonate treatment.

Routine BMD measurement “1-2 years after stopping prolonged alendronate therapy may not be useful for predicting the patient's fracture risk,” said Dr. Bauer, professor of medicine, epidemiology, and biostatistics at the University of California, San Francisco. The BMD at the time of alendronate discontinuation “was highly predictive of who was going to fracture.”

Patients who stopped alendronate therapy with a total hip BMD T score of −1.4 or greater had a 9% rate of clinical fracture during 5 years of follow-up. Patients with a T score of −2.1 to −1.5 when they stopped bisphosphonate treatment had a 23% fracture rate during 5 years of follow-up, and those who stopped with a T score lower than −2.1 had a 33% fracture rate over the next 5 years. The between-group differences were statistically significant.

These data “are helpful as I try to decide which of my patients I should leave on a bisphosphonate,” commented Dr. Elizabeth Shane, a professor of medicine at Columbia University in New York. “Patients below −2.1 were at very high risk of fracture, but even those in the middle tertile, with less than −1.5, were at a risk almost as high.” Dr. Bauer's data “provides me with some comfort [on whom] I can stop safely.”

Dr. Bauer and his associates used data collected in the FLEX (Fracture Intervention Trial Long-Term Extension) study, which randomized 1,099 postmenopausal women who had completed 5 years of alendronate treatment to either continue on alendronate for another 5 years or switch to placebo (JAMA 2006;296:2927-38). They focused on the 437 patients who switched to placebo, and assessed the BMD measures that were associated with fracture risk during follow-up.

Even among patients who had relatively substantial bone loss during 1 year of follow-up, the amount of lost BMD did not significantly correlate with their follow-up fracture rate. The researchers saw no significant link to fracture rate among the 21% of patients who lost at least 3% of their BMD during the first year of follow-up, or among the 8% of patients who lost at least 5% of their BMD during 1 year of follow-up.

When a patient starts bisphosphonate treatment, the BMD typically rises sharply for a couple of years, and then plateaus and remains stable, Dr. Bauer said. After patients stop bisphosphonate treatment, their BMD usually declines gradually. Prior analysis of the FLEX data showed that patients who failed to reach a BMD of at least −2.5 usually benefited with fewer fractures when they remained on treatment. The new findings suggest that patients with T scores of less than −1.5 may also benefit from continued treatment. However, when patients reach an adequate BMD (greater than −1.5), “it's not unreasonable to talk with the patient about the potential risks and benefits of a drug holiday,” Dr. Bauer said.

The FLEX study was funded by Merck, which markets alendronate (Fosamax). Dr. Bauer has received research funding from Amgen, Merck, and Novartis.

BMD at the time of alendronate discontinuation 'was highly predictive of who was going to fracture.'

Source DR. BAUER

Major Finding: Postmenopausal women with osteoporosis who received an annual injection of zoledronic acid for 6 years maintained their femoral neck bone mineral density significantly better than did those treated with the drug for 3 years followed by 3 years on placebo.

Data Source: Extension of the HORIZON Pivotal Fracture Trial, a randomized, multicenter extension trial with 1,233 women.

Disclosures: The HORIZON Pivotal Fracture Trial was funded by Novartis, which markets zoledronic acid (Aclasta). Dr. Black said that he has served as a consultant and done teaching for Amgen and Nycomed, and that he has received research contracts from Amgen, Merck, Novartis, and Roche/Genentech.

TORONTO — Patients who continued annual treatment with zoledronic acid for 6 years had significantly better bone mineral density and fewer morphometric vertebral fractures than did patients who received 3 years of treatment and then stopped, according to results of a controlled study with more than 1,200 subjects.

Six continuous years of annual zoledronic acid treatment also proved safe, making continued treatment with this bisphosphonate formulation an option for patients who might benefit, Dennis M. Black, Ph.D., said at the meeting.

“After 3 years, it might be beneficial for some women, particularly those at high vertebral fracture risk, to continue zoledronic acid for an additional 3 years,” said Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco.

“These new findings show that continued treatment with zoledronic acid for 6 years continues to maintain bone mass and reduced vertebral fracture risk with no change to its favorable safety profile compared with discontinuation of treatment after 3 years,” he said in a written statement.

On the other hand, the decision to continue bisphosphonate treatment long term must be individualized, he said.

It may be possible to identify women who would benefit from a drug holiday, he added.

In light of the new finding, zoledronic acid joins other bisphosphonates, such as alendronate, shown to prevent loss of bone density when the drug is continued after several years of treatment.

In a previous report, continuing treatment with alendronate for 5 years following an initial 5 years of treatment led to less bone density loss than in patients who switched from alendronate to placebo (JAMA 2006;296:2927-38).

The same alendronate study failed to show that continued bisphosphonate treatment led to a reduced rate of morphometric vertebral fractures, compared with stopping alendronate.

The new zoledronic acid findings came from an extension of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, which compared a single, annual infusion of zoledronic acid with placebo in postmenopausal women with osteoporosis during 3 years of treatment (N. Engl. J. Med. 2007;356:1809-22).

Dr. Black and his associates randomized 1,233 women who completed the zoledronic acid arm of the study to either continue with another 3 years of annual infusions of 5 mg zoledronic acid or switch to placebo.

The average age of the study subjects was 76 years, and approximately 55% had a femoral neck T score of less than −2.5.

At the conclusion of the study, the percent change in femoral neck bone mineral density, compared with the level at entry into the study, averaged 1% higher in patients who were treated with zoledronic acid, a statistically significant difference in the study's primary end point.

Femoral neck bone mineral density in the zoledronic acid–treated patients increased by an average of 1.4% over baseline 6 years earlier (when they started on the drug), compared with those who switched off the bisphosphonate after 3 years, a statistically significant difference.

The rate of morphometric vertebral fractures during the 3 years of the new study totaled 6% in the patients who were on placebo and 3% in those who were on zoledronic acid, a statistically significant difference.

The two treatment arms showed no significant difference in their rates of nonvertebral fractures. Continued zoledronic acid treatment also led to reduced blood levels of a marker of bone turnover compared with the patients who received placebo injections.

Six years of annual zoledronic acid treatment appeared safe, with no excess of adverse events or serious adverse events compared with the patients on 3 years of placebo. The researchers looked especially closely at cardiovascular events; the only significant, between-treatment difference was in new hypertensive adverse events, which occurred significantly more often in the patients who received placebo for 3 years.

The decision to continue bisphosphonate treatment long term must be individualized.

Source DR. BLACK

Major Finding: Postmenopausal women with osteoporosis who received an annual injection of zoledronic acid for 6 years maintained their femoral neck bone mineral density significantly better than did those treated with the drug for 3 years followed by 3 years on placebo.

Data Source: Extension of the HORIZON Pivotal Fracture Trial, a randomized, multicenter extension trial with 1,233 women.

Disclosures: The HORIZON Pivotal Fracture Trial was funded by Novartis, which markets zoledronic acid (Aclasta). Dr. Black said that he has served as a consultant and done teaching for Amgen and Nycomed, and that he has received research contracts from Amgen, Merck, Novartis, and Roche/Genentech.

TORONTO — Patients who continued annual treatment with zoledronic acid for 6 years had significantly better bone mineral density and fewer morphometric vertebral fractures than did patients who received 3 years of treatment and then stopped, according to results of a controlled study with more than 1,200 subjects.

Six continuous years of annual zoledronic acid treatment also proved safe, making continued treatment with this bisphosphonate formulation an option for patients who might benefit, Dennis M. Black, Ph.D., said at the meeting.

“After 3 years, it might be beneficial for some women, particularly those at high vertebral fracture risk, to continue zoledronic acid for an additional 3 years,” said Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco.

“These new findings show that continued treatment with zoledronic acid for 6 years continues to maintain bone mass and reduced vertebral fracture risk with no change to its favorable safety profile compared with discontinuation of treatment after 3 years,” he said in a written statement.

On the other hand, the decision to continue bisphosphonate treatment long term must be individualized, he said.

It may be possible to identify women who would benefit from a drug holiday, he added.

In light of the new finding, zoledronic acid joins other bisphosphonates, such as alendronate, shown to prevent loss of bone density when the drug is continued after several years of treatment.

In a previous report, continuing treatment with alendronate for 5 years following an initial 5 years of treatment led to less bone density loss than in patients who switched from alendronate to placebo (JAMA 2006;296:2927-38).

The same alendronate study failed to show that continued bisphosphonate treatment led to a reduced rate of morphometric vertebral fractures, compared with stopping alendronate.

The new zoledronic acid findings came from an extension of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, which compared a single, annual infusion of zoledronic acid with placebo in postmenopausal women with osteoporosis during 3 years of treatment (N. Engl. J. Med. 2007;356:1809-22).

Dr. Black and his associates randomized 1,233 women who completed the zoledronic acid arm of the study to either continue with another 3 years of annual infusions of 5 mg zoledronic acid or switch to placebo.

The average age of the study subjects was 76 years, and approximately 55% had a femoral neck T score of less than −2.5.

At the conclusion of the study, the percent change in femoral neck bone mineral density, compared with the level at entry into the study, averaged 1% higher in patients who were treated with zoledronic acid, a statistically significant difference in the study's primary end point.

Femoral neck bone mineral density in the zoledronic acid–treated patients increased by an average of 1.4% over baseline 6 years earlier (when they started on the drug), compared with those who switched off the bisphosphonate after 3 years, a statistically significant difference.

The rate of morphometric vertebral fractures during the 3 years of the new study totaled 6% in the patients who were on placebo and 3% in those who were on zoledronic acid, a statistically significant difference.

The two treatment arms showed no significant difference in their rates of nonvertebral fractures. Continued zoledronic acid treatment also led to reduced blood levels of a marker of bone turnover compared with the patients who received placebo injections.

Six years of annual zoledronic acid treatment appeared safe, with no excess of adverse events or serious adverse events compared with the patients on 3 years of placebo. The researchers looked especially closely at cardiovascular events; the only significant, between-treatment difference was in new hypertensive adverse events, which occurred significantly more often in the patients who received placebo for 3 years.

The decision to continue bisphosphonate treatment long term must be individualized.

Source DR. BLACK

Major Finding: Postmenopausal women with osteoporosis who received an annual injection of zoledronic acid for 6 years maintained their femoral neck bone mineral density significantly better than did those treated with the drug for 3 years followed by 3 years on placebo.

Data Source: Extension of the HORIZON Pivotal Fracture Trial, a randomized, multicenter extension trial with 1,233 women.

Disclosures: The HORIZON Pivotal Fracture Trial was funded by Novartis, which markets zoledronic acid (Aclasta). Dr. Black said that he has served as a consultant and done teaching for Amgen and Nycomed, and that he has received research contracts from Amgen, Merck, Novartis, and Roche/Genentech.

TORONTO — Patients who continued annual treatment with zoledronic acid for 6 years had significantly better bone mineral density and fewer morphometric vertebral fractures than did patients who received 3 years of treatment and then stopped, according to results of a controlled study with more than 1,200 subjects.

Six continuous years of annual zoledronic acid treatment also proved safe, making continued treatment with this bisphosphonate formulation an option for patients who might benefit, Dennis M. Black, Ph.D., said at the meeting.

“After 3 years, it might be beneficial for some women, particularly those at high vertebral fracture risk, to continue zoledronic acid for an additional 3 years,” said Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco.

“These new findings show that continued treatment with zoledronic acid for 6 years continues to maintain bone mass and reduced vertebral fracture risk with no change to its favorable safety profile compared with discontinuation of treatment after 3 years,” he said in a written statement.

On the other hand, the decision to continue bisphosphonate treatment long term must be individualized, he said.

It may be possible to identify women who would benefit from a drug holiday, he added.

In light of the new finding, zoledronic acid joins other bisphosphonates, such as alendronate, shown to prevent loss of bone density when the drug is continued after several years of treatment.

In a previous report, continuing treatment with alendronate for 5 years following an initial 5 years of treatment led to less bone density loss than in patients who switched from alendronate to placebo (JAMA 2006;296:2927-38).

The same alendronate study failed to show that continued bisphosphonate treatment led to a reduced rate of morphometric vertebral fractures, compared with stopping alendronate.

The new zoledronic acid findings came from an extension of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, which compared a single, annual infusion of zoledronic acid with placebo in postmenopausal women with osteoporosis during 3 years of treatment (N. Engl. J. Med. 2007;356:1809-22).

Dr. Black and his associates randomized 1,233 women who completed the zoledronic acid arm of the study to either continue with another 3 years of annual infusions of 5 mg zoledronic acid or switch to placebo.

The average age of the study subjects was 76 years, and approximately 55% had a femoral neck T score of less than −2.5.

At the conclusion of the study, the percent change in femoral neck bone mineral density, compared with the level at entry into the study, averaged 1% higher in patients who were treated with zoledronic acid, a statistically significant difference in the study's primary end point.

Femoral neck bone mineral density in the zoledronic acid–treated patients increased by an average of 1.4% over baseline 6 years earlier (when they started on the drug), compared with those who switched off the bisphosphonate after 3 years, a statistically significant difference.

The rate of morphometric vertebral fractures during the 3 years of the new study totaled 6% in the patients who were on placebo and 3% in those who were on zoledronic acid, a statistically significant difference.

The two treatment arms showed no significant difference in their rates of nonvertebral fractures. Continued zoledronic acid treatment also led to reduced blood levels of a marker of bone turnover compared with the patients who received placebo injections.

Six years of annual zoledronic acid treatment appeared safe, with no excess of adverse events or serious adverse events compared with the patients on 3 years of placebo. The researchers looked especially closely at cardiovascular events; the only significant, between-treatment difference was in new hypertensive adverse events, which occurred significantly more often in the patients who received placebo for 3 years.

The decision to continue bisphosphonate treatment long term must be individualized.

Source DR. BLACK

Major Finding: During 12 years of follow-up, patients aged 65–75 years had a 13% revision rate following total hip replacement. Patients older than 75 years at the time of their initial hip replacement had a 9% rate of revision surgery during the same 12-year follow-up.

Data Source: Medicare records for 58,521 beneficiaries who had total hip replacement surgery during July 1995–June 1996 and who were followed through 2008.

Disclosures: Dr. Katz said that he had no disclosures.

BRUSSELS — When younger patients receive a total hip replacement, they are more likely to eventually need revision surgery, compared with older patients, according to findings from a 12-year follow-up study of more than 58,000 Medicare patients.

The finding makes sense and comes as no surprise, but the documentation of a link between younger age and increased revision rates has important implications for prosthesis design.

“As total hip replacement indications extend to increasingly younger populations, [the patients'] mortality risk will diminish, and a vast majority will remain at risk for revision for decades,” Dr. Jeffrey N. Katz said at the congress

“Research evaluating technical innovations to increase prosthesis longevity should recognize the competing risk of mortality. In a 75- or 80-year-old, revision is a rather infrequent event; their implant will likely outsurvive them. The older a patient is, the more likely the patient is to die with their original prosthesis intact,” said Dr. Katz, director of the orthopedic and arthritis center for outcomes research at Brigham and Women's Hospital, Boston.

“If a prosthesis manufacturer wants to increase the longevity of a prosthesis, the patients to target are those younger than 65. For patients who get through the perioperative period, the real issue is biomaterials: How likely are the biomaterials to wear out over time?” he noted.

Currently, about 280,000 total hip replacements are performed in the United States annually (more than 90% because of osteoarthritis), along with 40,000 revision hip surgeries each year. Revisions alone cost more than $1 billion annually.

Dr. Katz and his associates studied the 58,521 Medicare beneficiaries who underwent a total hip replacement during July 1995–June 1996. Two-thirds were women, and 60% were aged 65–75 years, with the remaining patients older than 75 years. The researchers had complete follow-up records for all patients for the subsequent 12 years, through 2008.

During follow-up, 60% of the patients who were older than 75 years at the time of surgery died; during the 12-year follow-up, the survivors had a revision rate of 9%. Among patients aged 65–75 years at the time of their initial hip surgery, 30% died during follow-up, with the survivors having a 13% revision rate. In both age groups, men had a higher revision rate than did women.

“Younger patients are more active and heavier,” Dr. Katz said in an interview at the congress, which was organized by the Osteoarthritis Research Society International.

“Younger patients probably wear [prosthetic] joints out faster, and – given the same amount of wear – they are offered [revision] surgery more frequently. … We don't have data for 45- to 65-year-olds, but by extension, their mortality is unlikely over the following 20 years, while a revision is likely,” Dr. Katz said.

'In a 75- or 80-year-old, revision is a rather infrequent event; their implant will likely outsurvive them.'

Source DR. KATZ

Major Finding: During 12 years of follow-up, patients aged 65–75 years had a 13% revision rate following total hip replacement. Patients older than 75 years at the time of their initial hip replacement had a 9% rate of revision surgery during the same 12-year follow-up.

Data Source: Medicare records for 58,521 beneficiaries who had total hip replacement surgery during July 1995–June 1996 and who were followed through 2008.

Disclosures: Dr. Katz said that he had no disclosures.

BRUSSELS — When younger patients receive a total hip replacement, they are more likely to eventually need revision surgery, compared with older patients, according to findings from a 12-year follow-up study of more than 58,000 Medicare patients.

The finding makes sense and comes as no surprise, but the documentation of a link between younger age and increased revision rates has important implications for prosthesis design.

“As total hip replacement indications extend to increasingly younger populations, [the patients'] mortality risk will diminish, and a vast majority will remain at risk for revision for decades,” Dr. Jeffrey N. Katz said at the congress

“Research evaluating technical innovations to increase prosthesis longevity should recognize the competing risk of mortality. In a 75- or 80-year-old, revision is a rather infrequent event; their implant will likely outsurvive them. The older a patient is, the more likely the patient is to die with their original prosthesis intact,” said Dr. Katz, director of the orthopedic and arthritis center for outcomes research at Brigham and Women's Hospital, Boston.

“If a prosthesis manufacturer wants to increase the longevity of a prosthesis, the patients to target are those younger than 65. For patients who get through the perioperative period, the real issue is biomaterials: How likely are the biomaterials to wear out over time?” he noted.

Currently, about 280,000 total hip replacements are performed in the United States annually (more than 90% because of osteoarthritis), along with 40,000 revision hip surgeries each year. Revisions alone cost more than $1 billion annually.

Dr. Katz and his associates studied the 58,521 Medicare beneficiaries who underwent a total hip replacement during July 1995–June 1996. Two-thirds were women, and 60% were aged 65–75 years, with the remaining patients older than 75 years. The researchers had complete follow-up records for all patients for the subsequent 12 years, through 2008.

During follow-up, 60% of the patients who were older than 75 years at the time of surgery died; during the 12-year follow-up, the survivors had a revision rate of 9%. Among patients aged 65–75 years at the time of their initial hip surgery, 30% died during follow-up, with the survivors having a 13% revision rate. In both age groups, men had a higher revision rate than did women.

“Younger patients are more active and heavier,” Dr. Katz said in an interview at the congress, which was organized by the Osteoarthritis Research Society International.

“Younger patients probably wear [prosthetic] joints out faster, and – given the same amount of wear – they are offered [revision] surgery more frequently. … We don't have data for 45- to 65-year-olds, but by extension, their mortality is unlikely over the following 20 years, while a revision is likely,” Dr. Katz said.

'In a 75- or 80-year-old, revision is a rather infrequent event; their implant will likely outsurvive them.'

Source DR. KATZ

Major Finding: During 12 years of follow-up, patients aged 65–75 years had a 13% revision rate following total hip replacement. Patients older than 75 years at the time of their initial hip replacement had a 9% rate of revision surgery during the same 12-year follow-up.

Data Source: Medicare records for 58,521 beneficiaries who had total hip replacement surgery during July 1995–June 1996 and who were followed through 2008.

Disclosures: Dr. Katz said that he had no disclosures.

BRUSSELS — When younger patients receive a total hip replacement, they are more likely to eventually need revision surgery, compared with older patients, according to findings from a 12-year follow-up study of more than 58,000 Medicare patients.

The finding makes sense and comes as no surprise, but the documentation of a link between younger age and increased revision rates has important implications for prosthesis design.

“As total hip replacement indications extend to increasingly younger populations, [the patients'] mortality risk will diminish, and a vast majority will remain at risk for revision for decades,” Dr. Jeffrey N. Katz said at the congress

“Research evaluating technical innovations to increase prosthesis longevity should recognize the competing risk of mortality. In a 75- or 80-year-old, revision is a rather infrequent event; their implant will likely outsurvive them. The older a patient is, the more likely the patient is to die with their original prosthesis intact,” said Dr. Katz, director of the orthopedic and arthritis center for outcomes research at Brigham and Women's Hospital, Boston.

“If a prosthesis manufacturer wants to increase the longevity of a prosthesis, the patients to target are those younger than 65. For patients who get through the perioperative period, the real issue is biomaterials: How likely are the biomaterials to wear out over time?” he noted.

Currently, about 280,000 total hip replacements are performed in the United States annually (more than 90% because of osteoarthritis), along with 40,000 revision hip surgeries each year. Revisions alone cost more than $1 billion annually.

Dr. Katz and his associates studied the 58,521 Medicare beneficiaries who underwent a total hip replacement during July 1995–June 1996. Two-thirds were women, and 60% were aged 65–75 years, with the remaining patients older than 75 years. The researchers had complete follow-up records for all patients for the subsequent 12 years, through 2008.

During follow-up, 60% of the patients who were older than 75 years at the time of surgery died; during the 12-year follow-up, the survivors had a revision rate of 9%. Among patients aged 65–75 years at the time of their initial hip surgery, 30% died during follow-up, with the survivors having a 13% revision rate. In both age groups, men had a higher revision rate than did women.

“Younger patients are more active and heavier,” Dr. Katz said in an interview at the congress, which was organized by the Osteoarthritis Research Society International.

“Younger patients probably wear [prosthetic] joints out faster, and – given the same amount of wear – they are offered [revision] surgery more frequently. … We don't have data for 45- to 65-year-olds, but by extension, their mortality is unlikely over the following 20 years, while a revision is likely,” Dr. Katz said.

'In a 75- or 80-year-old, revision is a rather infrequent event; their implant will likely outsurvive them.'

Source DR. KATZ

BRUSSELS — Vitamin K deficiency may increase the risk for developing knee osteoarthritis and for forming knee cartilage lesions, judging from the findings of a 30-month study of nearly 1,200 people at risk for knee osteoarthritis.

This apparent role of low vitamin K levels in susceptibility to knee pathology raised the question of whether vitamin K supplementation for deficient individuals might be a “simple, effective preventive agent,” Dr. Tuhina Neogi said at the congress.

“The next step is an intervention trial,” said Dr. Neogi, a rheumatologist at Boston University. “Taken together, there is enough biological plausibility that vitamin K could play a role. … If [dietary supplementation] proves effective, it would be something easy for people to do for themselves.”

Results from prior studies showed that low vitamin K intake and low blood levels were linked with prevalent radiographic features of hand and knee osteoarthritis. The new study made the first longitudinal examination of a potential link between plasma levels of vitamin K at baseline and incident osteoarthritis and associated pathology.

The investigators examined data that was collected from 1,180 people who had an elevated risk for knee osteoarthritis at entry but had not yet developed the disease. They averaged 62 years of age; 62% were women, and their average body mass index was about 30 kg/m

The researchers made incidence osteoarthritis the primary end point, defined as development of a knee Kellgren-Lawrence (KL) grade of 2 or higher (including knee replacement). All people included in the analysis had a KL grade less than 2 at baseline. During 30 months of follow-up, 15% of the participants developed osteoarthritis.

In an analysis of whether or not participants developed knee osteoarthritis, those with vitamin K deficiency at baseline had a 43% increased risk, after adjustment for age, sex, BMI, bone mineral density, and vitamin D level at baseline. This increased risk just missed reaching statistical significance. Dr. Neogi suggested that this may have been a power issue, with too few vitamin K–deficient participants in the database.

An additional analysis that took into account the extent of knee osteoarthritis showed statistically significant links with vitamin K deficiency.

Those who developed osteoarthritis in both knees had a significant, nearly threefold increased risk of having vitamin K deficiency at baseline, compared with those who developed osteoarthritis in one knee during follow-up. Those who had both knees affected at follow-up had a significant, twofold increased risk of vitamin deficiency, compared with people who did not develop any knee osteoarthritis, she reported at the congress, which was organized by the Osteoarthritis Research Society International.

The vitamin K–deficient participants also had a statistically significant, nearly threefold increased risk of developing new cartilage lesions on their knee MRI scans that were consistent with developing osteoarthritis. They also had a 77% increased risk for showing osteophytes on their follow-up MRI scans, but this difference was not statistically significant

Dr. Neogi said that she had no disclosures.

BRUSSELS — Vitamin K deficiency may increase the risk for developing knee osteoarthritis and for forming knee cartilage lesions, judging from the findings of a 30-month study of nearly 1,200 people at risk for knee osteoarthritis.

This apparent role of low vitamin K levels in susceptibility to knee pathology raised the question of whether vitamin K supplementation for deficient individuals might be a “simple, effective preventive agent,” Dr. Tuhina Neogi said at the congress.

“The next step is an intervention trial,” said Dr. Neogi, a rheumatologist at Boston University. “Taken together, there is enough biological plausibility that vitamin K could play a role. … If [dietary supplementation] proves effective, it would be something easy for people to do for themselves.”

Results from prior studies showed that low vitamin K intake and low blood levels were linked with prevalent radiographic features of hand and knee osteoarthritis. The new study made the first longitudinal examination of a potential link between plasma levels of vitamin K at baseline and incident osteoarthritis and associated pathology.

The investigators examined data that was collected from 1,180 people who had an elevated risk for knee osteoarthritis at entry but had not yet developed the disease. They averaged 62 years of age; 62% were women, and their average body mass index was about 30 kg/m

The researchers made incidence osteoarthritis the primary end point, defined as development of a knee Kellgren-Lawrence (KL) grade of 2 or higher (including knee replacement). All people included in the analysis had a KL grade less than 2 at baseline. During 30 months of follow-up, 15% of the participants developed osteoarthritis.

In an analysis of whether or not participants developed knee osteoarthritis, those with vitamin K deficiency at baseline had a 43% increased risk, after adjustment for age, sex, BMI, bone mineral density, and vitamin D level at baseline. This increased risk just missed reaching statistical significance. Dr. Neogi suggested that this may have been a power issue, with too few vitamin K–deficient participants in the database.

An additional analysis that took into account the extent of knee osteoarthritis showed statistically significant links with vitamin K deficiency.

Those who developed osteoarthritis in both knees had a significant, nearly threefold increased risk of having vitamin K deficiency at baseline, compared with those who developed osteoarthritis in one knee during follow-up. Those who had both knees affected at follow-up had a significant, twofold increased risk of vitamin deficiency, compared with people who did not develop any knee osteoarthritis, she reported at the congress, which was organized by the Osteoarthritis Research Society International.

The vitamin K–deficient participants also had a statistically significant, nearly threefold increased risk of developing new cartilage lesions on their knee MRI scans that were consistent with developing osteoarthritis. They also had a 77% increased risk for showing osteophytes on their follow-up MRI scans, but this difference was not statistically significant

Dr. Neogi said that she had no disclosures.

BRUSSELS — Vitamin K deficiency may increase the risk for developing knee osteoarthritis and for forming knee cartilage lesions, judging from the findings of a 30-month study of nearly 1,200 people at risk for knee osteoarthritis.

This apparent role of low vitamin K levels in susceptibility to knee pathology raised the question of whether vitamin K supplementation for deficient individuals might be a “simple, effective preventive agent,” Dr. Tuhina Neogi said at the congress.

“The next step is an intervention trial,” said Dr. Neogi, a rheumatologist at Boston University. “Taken together, there is enough biological plausibility that vitamin K could play a role. … If [dietary supplementation] proves effective, it would be something easy for people to do for themselves.”

Results from prior studies showed that low vitamin K intake and low blood levels were linked with prevalent radiographic features of hand and knee osteoarthritis. The new study made the first longitudinal examination of a potential link between plasma levels of vitamin K at baseline and incident osteoarthritis and associated pathology.

The investigators examined data that was collected from 1,180 people who had an elevated risk for knee osteoarthritis at entry but had not yet developed the disease. They averaged 62 years of age; 62% were women, and their average body mass index was about 30 kg/m

The researchers made incidence osteoarthritis the primary end point, defined as development of a knee Kellgren-Lawrence (KL) grade of 2 or higher (including knee replacement). All people included in the analysis had a KL grade less than 2 at baseline. During 30 months of follow-up, 15% of the participants developed osteoarthritis.

In an analysis of whether or not participants developed knee osteoarthritis, those with vitamin K deficiency at baseline had a 43% increased risk, after adjustment for age, sex, BMI, bone mineral density, and vitamin D level at baseline. This increased risk just missed reaching statistical significance. Dr. Neogi suggested that this may have been a power issue, with too few vitamin K–deficient participants in the database.

An additional analysis that took into account the extent of knee osteoarthritis showed statistically significant links with vitamin K deficiency.

Those who developed osteoarthritis in both knees had a significant, nearly threefold increased risk of having vitamin K deficiency at baseline, compared with those who developed osteoarthritis in one knee during follow-up. Those who had both knees affected at follow-up had a significant, twofold increased risk of vitamin deficiency, compared with people who did not develop any knee osteoarthritis, she reported at the congress, which was organized by the Osteoarthritis Research Society International.

The vitamin K–deficient participants also had a statistically significant, nearly threefold increased risk of developing new cartilage lesions on their knee MRI scans that were consistent with developing osteoarthritis. They also had a 77% increased risk for showing osteophytes on their follow-up MRI scans, but this difference was not statistically significant

Dr. Neogi said that she had no disclosures.

Major Finding: Bone trabecular integrity, assessed by fractal signature analysis of plain radiographs, correctly predicted about 85% of the joint space change in patients with knee OA.

Data Source: Review of radiographs taken from 60 patients with OA and 67 controls at baseline and at 12 and 24 months' follow-up.

Disclosures: Dr. Kraus said that she had no relevant disclosures. One coauthor is an employee of Optasia Medical; Optasia provided the software used for the radiograph analyses. Another coauthor is an employee of Pfizer; Pfizer supplied the database used in the study.

BRUSSELS — Analysis of plain x-ray images of knee joints from 60 patients with osteoarthritis confirmed that a novel method for assessing bone trabecular structure adjacent to knee joints provides a reliable prediction of future disease progression.

Assessment of bone trabecular integrity by fractal signature analysis “provides an osteoarthritis imaging biomarker that is a prognostic marker of knee osteoarthritis progression,” Dr. Virginia Byers Kraus said at the congress.

Baseline bone trabecular integrity predicted roughly 85% of the change in joint space area during 2 years of follow-up in patients with osteoarthritis (OA). The new study, which used x-rays from 60 patients with OA and 67 controls, is the second report to document the prognostic accuracy of fractal signature analysis of bone trabecular integrity in OA patients.

The first report, also from Dr. Kraus and her associates, came out last year, and involved 138 OA patients who were followed for 3 years (Arthritis Rheum. 2009;60:3711–22).

“The next step is to compare fractal signature analysis head to head with MRI and look at its ability to predict MRI changes” in OA patients, and “its ability to identify OA in the preradiographic stage,” she said in an interview.

Fractal signature analysis of bone trabecular integrity using x-ray images “gives you the ability to more fully phenotype patients than we've been able to, and it is less costly than MRI,” said Dr. Kraus, a rheumatologist and professor of medicine at Duke University in Durham, N.C. “It's very promising for identifying patients at high risk for progression in [an intervention] trial, and possibly to screen patients in the clinic.”

Fractal signature analysis evaluates the complexity of detail of a two-dimensional image. Past studies have successfully used the method to assess osteoporosis and arthritis of the spine, hip, wrists, hands, and knees before and after surgery. Fractal signature analysis has the major advantage of not being very sensitive to image-acquisition quality.

Although fractal signature analysis involves a complex statistical analysis of x-ray image data of bone structure adjacent to a patient's knee joint, Dr. Kraus and her associates incorporated that analysis into “KneeAnalyzer” software developed by Optasia Medical, a British company. Now that the software exists, “it is easy to use. It's just a tool to get at bone trabecular integrity. I think it can easily be widely adopted,” she said.

The new study used data collected in a nontherapeutic methods trial sponsored by Pfizer Inc. The data set included 60 women with knee OA whose average age wa 58 years and whose average body mass index was 35.6 kg/m

The researchers assessed bone trabecular integrity using fractal signature analysis on radiographs taken at baseline and at 12 and 24 months. The baseline measurements in the vertical dimension of bone trabecular integrity predicted changes in joint space area at 12 and 24 months, and in joint space width at 24 months. Baseline measures in the horizontal dimension were not predictive. The predicted changes based on baseline bone trabecular integrity accounted for 85%–87% of the actual change in joint space area over 24 months, Dr. Kraus reported at the congress, which was organized by the Osteoarthritis Research Society International.

Major Finding: Bone trabecular integrity, assessed by fractal signature analysis of plain radiographs, correctly predicted about 85% of the joint space change in patients with knee OA.

Data Source: Review of radiographs taken from 60 patients with OA and 67 controls at baseline and at 12 and 24 months' follow-up.

Disclosures: Dr. Kraus said that she had no relevant disclosures. One coauthor is an employee of Optasia Medical; Optasia provided the software used for the radiograph analyses. Another coauthor is an employee of Pfizer; Pfizer supplied the database used in the study.

BRUSSELS — Analysis of plain x-ray images of knee joints from 60 patients with osteoarthritis confirmed that a novel method for assessing bone trabecular structure adjacent to knee joints provides a reliable prediction of future disease progression.

Assessment of bone trabecular integrity by fractal signature analysis “provides an osteoarthritis imaging biomarker that is a prognostic marker of knee osteoarthritis progression,” Dr. Virginia Byers Kraus said at the congress.

Baseline bone trabecular integrity predicted roughly 85% of the change in joint space area during 2 years of follow-up in patients with osteoarthritis (OA). The new study, which used x-rays from 60 patients with OA and 67 controls, is the second report to document the prognostic accuracy of fractal signature analysis of bone trabecular integrity in OA patients.

The first report, also from Dr. Kraus and her associates, came out last year, and involved 138 OA patients who were followed for 3 years (Arthritis Rheum. 2009;60:3711–22).

“The next step is to compare fractal signature analysis head to head with MRI and look at its ability to predict MRI changes” in OA patients, and “its ability to identify OA in the preradiographic stage,” she said in an interview.

Fractal signature analysis of bone trabecular integrity using x-ray images “gives you the ability to more fully phenotype patients than we've been able to, and it is less costly than MRI,” said Dr. Kraus, a rheumatologist and professor of medicine at Duke University in Durham, N.C. “It's very promising for identifying patients at high risk for progression in [an intervention] trial, and possibly to screen patients in the clinic.”

Fractal signature analysis evaluates the complexity of detail of a two-dimensional image. Past studies have successfully used the method to assess osteoporosis and arthritis of the spine, hip, wrists, hands, and knees before and after surgery. Fractal signature analysis has the major advantage of not being very sensitive to image-acquisition quality.

Although fractal signature analysis involves a complex statistical analysis of x-ray image data of bone structure adjacent to a patient's knee joint, Dr. Kraus and her associates incorporated that analysis into “KneeAnalyzer” software developed by Optasia Medical, a British company. Now that the software exists, “it is easy to use. It's just a tool to get at bone trabecular integrity. I think it can easily be widely adopted,” she said.

The new study used data collected in a nontherapeutic methods trial sponsored by Pfizer Inc. The data set included 60 women with knee OA whose average age wa 58 years and whose average body mass index was 35.6 kg/m

The researchers assessed bone trabecular integrity using fractal signature analysis on radiographs taken at baseline and at 12 and 24 months. The baseline measurements in the vertical dimension of bone trabecular integrity predicted changes in joint space area at 12 and 24 months, and in joint space width at 24 months. Baseline measures in the horizontal dimension were not predictive. The predicted changes based on baseline bone trabecular integrity accounted for 85%–87% of the actual change in joint space area over 24 months, Dr. Kraus reported at the congress, which was organized by the Osteoarthritis Research Society International.

Major Finding: Bone trabecular integrity, assessed by fractal signature analysis of plain radiographs, correctly predicted about 85% of the joint space change in patients with knee OA.

Data Source: Review of radiographs taken from 60 patients with OA and 67 controls at baseline and at 12 and 24 months' follow-up.

Disclosures: Dr. Kraus said that she had no relevant disclosures. One coauthor is an employee of Optasia Medical; Optasia provided the software used for the radiograph analyses. Another coauthor is an employee of Pfizer; Pfizer supplied the database used in the study.

BRUSSELS — Analysis of plain x-ray images of knee joints from 60 patients with osteoarthritis confirmed that a novel method for assessing bone trabecular structure adjacent to knee joints provides a reliable prediction of future disease progression.

Assessment of bone trabecular integrity by fractal signature analysis “provides an osteoarthritis imaging biomarker that is a prognostic marker of knee osteoarthritis progression,” Dr. Virginia Byers Kraus said at the congress.

Baseline bone trabecular integrity predicted roughly 85% of the change in joint space area during 2 years of follow-up in patients with osteoarthritis (OA). The new study, which used x-rays from 60 patients with OA and 67 controls, is the second report to document the prognostic accuracy of fractal signature analysis of bone trabecular integrity in OA patients.

The first report, also from Dr. Kraus and her associates, came out last year, and involved 138 OA patients who were followed for 3 years (Arthritis Rheum. 2009;60:3711–22).

“The next step is to compare fractal signature analysis head to head with MRI and look at its ability to predict MRI changes” in OA patients, and “its ability to identify OA in the preradiographic stage,” she said in an interview.

Fractal signature analysis of bone trabecular integrity using x-ray images “gives you the ability to more fully phenotype patients than we've been able to, and it is less costly than MRI,” said Dr. Kraus, a rheumatologist and professor of medicine at Duke University in Durham, N.C. “It's very promising for identifying patients at high risk for progression in [an intervention] trial, and possibly to screen patients in the clinic.”

Fractal signature analysis evaluates the complexity of detail of a two-dimensional image. Past studies have successfully used the method to assess osteoporosis and arthritis of the spine, hip, wrists, hands, and knees before and after surgery. Fractal signature analysis has the major advantage of not being very sensitive to image-acquisition quality.

Although fractal signature analysis involves a complex statistical analysis of x-ray image data of bone structure adjacent to a patient's knee joint, Dr. Kraus and her associates incorporated that analysis into “KneeAnalyzer” software developed by Optasia Medical, a British company. Now that the software exists, “it is easy to use. It's just a tool to get at bone trabecular integrity. I think it can easily be widely adopted,” she said.

The new study used data collected in a nontherapeutic methods trial sponsored by Pfizer Inc. The data set included 60 women with knee OA whose average age wa 58 years and whose average body mass index was 35.6 kg/m

The researchers assessed bone trabecular integrity using fractal signature analysis on radiographs taken at baseline and at 12 and 24 months. The baseline measurements in the vertical dimension of bone trabecular integrity predicted changes in joint space area at 12 and 24 months, and in joint space width at 24 months. Baseline measures in the horizontal dimension were not predictive. The predicted changes based on baseline bone trabecular integrity accounted for 85%–87% of the actual change in joint space area over 24 months, Dr. Kraus reported at the congress, which was organized by the Osteoarthritis Research Society International.

BRUSSELS — Statin therapy may exert yet another beneficial clinical effect – preventing development of knee osteoarthritis and slowing its progression – based on an analysis of more than 3,000 people who were enrolled in a prospective cohort study.

In an analysis of people in the Rotterdam Study, statin use was significantly linked with a more-than-50% reduced rate of knee osteoarthritis (OA) incidence, and a more-than-50% reduced rate of knee OA progression after adjustment for several baseline risk factors, Dr. Stefan Clockaerts said at the congress. In contrast, statin use had no significant impact on the incidence or progression of hip OA.

The findings suggest that knee OA may be at least partly a metabolic disease, said Dr. Clockaerts of Erasmus University, Rotterdam, the Netherlands, and the University of Antwerp (Belgium).

“We think that there is a difference in the pathogenesis of hip and knee osteoarthritis, and that several systemic factors – such as cholesterol, body mass index, and diabetes – appear to influence knee osteoarthritis” but not deterioration of the hip, Dr. Clockaerts said in an interview.

“Our idea is that metabolic alterations are more important for knee osteoarthritis than for hip osteoarthritis.”

For example, Dr. Clockaerts cited prior reports that cholesterol may have a damaging effect on cartilage, and it may increase the formation and activity of bone marrow lesions. “Cholesterol is probably not good for knee osteoarthritis,” he said. Synovial fluid contains cholesterol, and statin treatment would reduce the level.

An additional hypothesis is that vascular pathology may contribute to the OA disease process, and that the beneficial effects of statin treatment on atherosclerosis and vascular function may also link statins and knee OA. The anti-inflammatory effect of statins most likely also plays a role.

“The systemic and intra-articular anti-inflammatory effects of statins are the most plausible explanations for the effect,” Dr. Clockaerts said.

The Rotterdam Study began in 1990 and enrolled 7,983 men and women aged 55 years or older into a longitudinal cohort study.

The analysis by Dr. Clockaerts and his associates focused on participants with knee and hip x-rays that were available from baseline and follow-up and were evaluable for scoring on the Kellgren-Lawrence (KL) scale. They excluded study participants with a history of rheumatoid arthritis, gout, ankylosing spondylitis, or a leg fracture that was treated with a prosthesis.

Information on statin use came from computerized pharmacy records for the Rotterdam suburb where participants lived. The analysis considered to be a statin user anyone who received a statin prescription for at least 100 days for at least 50% of the drug's recommended daily dosage.

They identified incident OA of the knee or hip in people with a baseline KL score of 0 or 1 that subsequently became 2 or greater.

They defined a case of OA progression to be a person with a baseline KL score of 1, 2, or 3 whose score later increased by at least 1 point. Average follow-up was 6 years.

The analysis showed that among 3,056 people who were evaluable for incident knee OA, statin users had a statistically significant, 57% reduced rate of knee OA, compared with nonusers, after adjustment for baseline age, diabetes, BMI, total cholesterol:HDL cholesterol ratio, and bone mineral density, said Dr. Clockaerts at the congress, which was presented by the Osteoarthritis Research Society International. (See box.)

Progression of knee osteoarthritis among 1,412 people with a baseline KL score of 1–3 occurred 53% less often in the statin users, compared with nonusers after adjustment for age, BMI, and BMD, which was a statistically significant difference.

The analysis did not look at the impact of specific statin types.

A similar analysis showed no significant interaction of statin use and the incidence of new-onset or progressing hip OA in more than 4,000 people who were evaluable for one of these end points, according to Dr. Clockaerts.

Further studies should directly test a statin's effect in an animal model for OA, such as the STR/ort mouse, which also shows metabolic derangements, he said.

Dr. Clockaerts said that he had no disclosures.

Vitals

Source Elsevier Global Medical News

BRUSSELS — Statin therapy may exert yet another beneficial clinical effect – preventing development of knee osteoarthritis and slowing its progression – based on an analysis of more than 3,000 people who were enrolled in a prospective cohort study.

In an analysis of people in the Rotterdam Study, statin use was significantly linked with a more-than-50% reduced rate of knee osteoarthritis (OA) incidence, and a more-than-50% reduced rate of knee OA progression after adjustment for several baseline risk factors, Dr. Stefan Clockaerts said at the congress. In contrast, statin use had no significant impact on the incidence or progression of hip OA.

The findings suggest that knee OA may be at least partly a metabolic disease, said Dr. Clockaerts of Erasmus University, Rotterdam, the Netherlands, and the University of Antwerp (Belgium).

“We think that there is a difference in the pathogenesis of hip and knee osteoarthritis, and that several systemic factors – such as cholesterol, body mass index, and diabetes – appear to influence knee osteoarthritis” but not deterioration of the hip, Dr. Clockaerts said in an interview.

“Our idea is that metabolic alterations are more important for knee osteoarthritis than for hip osteoarthritis.”

For example, Dr. Clockaerts cited prior reports that cholesterol may have a damaging effect on cartilage, and it may increase the formation and activity of bone marrow lesions. “Cholesterol is probably not good for knee osteoarthritis,” he said. Synovial fluid contains cholesterol, and statin treatment would reduce the level.

An additional hypothesis is that vascular pathology may contribute to the OA disease process, and that the beneficial effects of statin treatment on atherosclerosis and vascular function may also link statins and knee OA. The anti-inflammatory effect of statins most likely also plays a role.

“The systemic and intra-articular anti-inflammatory effects of statins are the most plausible explanations for the effect,” Dr. Clockaerts said.

The Rotterdam Study began in 1990 and enrolled 7,983 men and women aged 55 years or older into a longitudinal cohort study.

The analysis by Dr. Clockaerts and his associates focused on participants with knee and hip x-rays that were available from baseline and follow-up and were evaluable for scoring on the Kellgren-Lawrence (KL) scale. They excluded study participants with a history of rheumatoid arthritis, gout, ankylosing spondylitis, or a leg fracture that was treated with a prosthesis.

Information on statin use came from computerized pharmacy records for the Rotterdam suburb where participants lived. The analysis considered to be a statin user anyone who received a statin prescription for at least 100 days for at least 50% of the drug's recommended daily dosage.

They identified incident OA of the knee or hip in people with a baseline KL score of 0 or 1 that subsequently became 2 or greater.

They defined a case of OA progression to be a person with a baseline KL score of 1, 2, or 3 whose score later increased by at least 1 point. Average follow-up was 6 years.

The analysis showed that among 3,056 people who were evaluable for incident knee OA, statin users had a statistically significant, 57% reduced rate of knee OA, compared with nonusers, after adjustment for baseline age, diabetes, BMI, total cholesterol:HDL cholesterol ratio, and bone mineral density, said Dr. Clockaerts at the congress, which was presented by the Osteoarthritis Research Society International. (See box.)

Progression of knee osteoarthritis among 1,412 people with a baseline KL score of 1–3 occurred 53% less often in the statin users, compared with nonusers after adjustment for age, BMI, and BMD, which was a statistically significant difference.

The analysis did not look at the impact of specific statin types.

A similar analysis showed no significant interaction of statin use and the incidence of new-onset or progressing hip OA in more than 4,000 people who were evaluable for one of these end points, according to Dr. Clockaerts.

Further studies should directly test a statin's effect in an animal model for OA, such as the STR/ort mouse, which also shows metabolic derangements, he said.

Dr. Clockaerts said that he had no disclosures.

Vitals

Source Elsevier Global Medical News

BRUSSELS — Statin therapy may exert yet another beneficial clinical effect – preventing development of knee osteoarthritis and slowing its progression – based on an analysis of more than 3,000 people who were enrolled in a prospective cohort study.

In an analysis of people in the Rotterdam Study, statin use was significantly linked with a more-than-50% reduced rate of knee osteoarthritis (OA) incidence, and a more-than-50% reduced rate of knee OA progression after adjustment for several baseline risk factors, Dr. Stefan Clockaerts said at the congress. In contrast, statin use had no significant impact on the incidence or progression of hip OA.

The findings suggest that knee OA may be at least partly a metabolic disease, said Dr. Clockaerts of Erasmus University, Rotterdam, the Netherlands, and the University of Antwerp (Belgium).

“We think that there is a difference in the pathogenesis of hip and knee osteoarthritis, and that several systemic factors – such as cholesterol, body mass index, and diabetes – appear to influence knee osteoarthritis” but not deterioration of the hip, Dr. Clockaerts said in an interview.

“Our idea is that metabolic alterations are more important for knee osteoarthritis than for hip osteoarthritis.”

For example, Dr. Clockaerts cited prior reports that cholesterol may have a damaging effect on cartilage, and it may increase the formation and activity of bone marrow lesions. “Cholesterol is probably not good for knee osteoarthritis,” he said. Synovial fluid contains cholesterol, and statin treatment would reduce the level.

An additional hypothesis is that vascular pathology may contribute to the OA disease process, and that the beneficial effects of statin treatment on atherosclerosis and vascular function may also link statins and knee OA. The anti-inflammatory effect of statins most likely also plays a role.

“The systemic and intra-articular anti-inflammatory effects of statins are the most plausible explanations for the effect,” Dr. Clockaerts said.

The Rotterdam Study began in 1990 and enrolled 7,983 men and women aged 55 years or older into a longitudinal cohort study.

The analysis by Dr. Clockaerts and his associates focused on participants with knee and hip x-rays that were available from baseline and follow-up and were evaluable for scoring on the Kellgren-Lawrence (KL) scale. They excluded study participants with a history of rheumatoid arthritis, gout, ankylosing spondylitis, or a leg fracture that was treated with a prosthesis.

Information on statin use came from computerized pharmacy records for the Rotterdam suburb where participants lived. The analysis considered to be a statin user anyone who received a statin prescription for at least 100 days for at least 50% of the drug's recommended daily dosage.

They identified incident OA of the knee or hip in people with a baseline KL score of 0 or 1 that subsequently became 2 or greater.

They defined a case of OA progression to be a person with a baseline KL score of 1, 2, or 3 whose score later increased by at least 1 point. Average follow-up was 6 years.

The analysis showed that among 3,056 people who were evaluable for incident knee OA, statin users had a statistically significant, 57% reduced rate of knee OA, compared with nonusers, after adjustment for baseline age, diabetes, BMI, total cholesterol:HDL cholesterol ratio, and bone mineral density, said Dr. Clockaerts at the congress, which was presented by the Osteoarthritis Research Society International. (See box.)

Progression of knee osteoarthritis among 1,412 people with a baseline KL score of 1–3 occurred 53% less often in the statin users, compared with nonusers after adjustment for age, BMI, and BMD, which was a statistically significant difference.

The analysis did not look at the impact of specific statin types.

A similar analysis showed no significant interaction of statin use and the incidence of new-onset or progressing hip OA in more than 4,000 people who were evaluable for one of these end points, according to Dr. Clockaerts.

Further studies should directly test a statin's effect in an animal model for OA, such as the STR/ort mouse, which also shows metabolic derangements, he said.

Dr. Clockaerts said that he had no disclosures.

Vitals

Source Elsevier Global Medical News

Major Finding: A single, 150-mg intra-articular injection of anakinra an average of 15 days after knee injury led to a statistically and clinically significant 10.5-point improvement in the KOOS activity of daily living score 4 days after injection. Patients receiving a placebo injection showed no significant improvement.

Data Source: Randomized, placebo-controlled pilot study with 11 patients.

Disclosures: Dr. Kraus's study did not have commercial funding. She said she had no relevant financial conflicts.

BRUSSELS — The clinical response seen to injection of a targeted anti-inflammatory drug into an acutely damaged knee joint within a few weeks of injury in a controlled pilot study with 11 patients provided a step toward the development of a new approach to treating traumatic joint injury.

“We should start to treat joint injury much more emergently, like an acute myocardial infarction.” Acute joint injury “is a critical event where early intervention might improve long-term outcome,” including heading off the eventual development of osteoarthritis, Dr. Virginia Byers Kraus said at the meeting.

“Blocking sterile inflammation early in acute, joint injury may be a means to stop development of chronic tissue injury and post-traumatic osteoarthritis,” said Dr. Kraus, professor of medicine at Duke University in Durham, N.C. “The early phase of acute joint injury represents a window of opportunity for providing treatment to promote healing and to prevent a subsequent cascade of joint destructive processes.

The study enrolled 11 patients younger than 40 within the first month following an MRI-confirmed tear of their anterior cruciate ligament in one knee. Following randomization, six patients received a single, 150-mg intra-articular injection of anakinra, which is an interleukin-1 (IL-1) receptor antagonist that blocks the effects of IL-1, a primary proinflammatory cytokine. The other five patients received saline injections. Anakinra (Kineret) has U.S. approval for the treatment of rheumatoid arthritis by subcutaneous injection, but carries no approval for the treatment of osteoarthritis or for intra-articular injection.

The age of the 11 patients averaged 24 years (range, 18–29 years). They received their injections an average of 15 days after their injury (range, 6–27 days).

Four days after treatment, patients who received an anakinra injection had significant and clinically meaningful improvements in several measures on the Knee Injury and Osteoarthritis Outcome Score (KOOS), improvements not seen in placebo patients, she reported.

The KOOS pain subscore fell by an average of 3.8 points in anakinra-treated patients, a statistically significant 23% relative improvement, compared with no significant change in placebo patients. The KOOS activities of daily living subscore showed a similar pattern, falling by a statistically significant 10.5 points in the anakinra-treated group, a 46% relative improvement compared with baseline.

Prior results showed that a change of 8–10 points in this measure corresponded to a clinically significant change after reconstruction of the anterior cruciate ligament, Dr. Kraus said at the congress, sponsored by the Osteoarthritis Research Society International.

The total KOOS score improved by an average of 20 points in the drug-treated patients, a significant 24% relative improvement, compared with no significant change in the placebo patients.

The anakinra-treated patients also showed strong trends toward further improvements in total KOOS score and activity subscore when they underwent another assessment 14 days after their injection, while the placebo patients continued to show no substantial changes.

Major Finding: A single, 150-mg intra-articular injection of anakinra an average of 15 days after knee injury led to a statistically and clinically significant 10.5-point improvement in the KOOS activity of daily living score 4 days after injection. Patients receiving a placebo injection showed no significant improvement.

Data Source: Randomized, placebo-controlled pilot study with 11 patients.

Disclosures: Dr. Kraus's study did not have commercial funding. She said she had no relevant financial conflicts.

BRUSSELS — The clinical response seen to injection of a targeted anti-inflammatory drug into an acutely damaged knee joint within a few weeks of injury in a controlled pilot study with 11 patients provided a step toward the development of a new approach to treating traumatic joint injury.

“We should start to treat joint injury much more emergently, like an acute myocardial infarction.” Acute joint injury “is a critical event where early intervention might improve long-term outcome,” including heading off the eventual development of osteoarthritis, Dr. Virginia Byers Kraus said at the meeting.

“Blocking sterile inflammation early in acute, joint injury may be a means to stop development of chronic tissue injury and post-traumatic osteoarthritis,” said Dr. Kraus, professor of medicine at Duke University in Durham, N.C. “The early phase of acute joint injury represents a window of opportunity for providing treatment to promote healing and to prevent a subsequent cascade of joint destructive processes.

The study enrolled 11 patients younger than 40 within the first month following an MRI-confirmed tear of their anterior cruciate ligament in one knee. Following randomization, six patients received a single, 150-mg intra-articular injection of anakinra, which is an interleukin-1 (IL-1) receptor antagonist that blocks the effects of IL-1, a primary proinflammatory cytokine. The other five patients received saline injections. Anakinra (Kineret) has U.S. approval for the treatment of rheumatoid arthritis by subcutaneous injection, but carries no approval for the treatment of osteoarthritis or for intra-articular injection.

The age of the 11 patients averaged 24 years (range, 18–29 years). They received their injections an average of 15 days after their injury (range, 6–27 days).

Four days after treatment, patients who received an anakinra injection had significant and clinically meaningful improvements in several measures on the Knee Injury and Osteoarthritis Outcome Score (KOOS), improvements not seen in placebo patients, she reported.

The KOOS pain subscore fell by an average of 3.8 points in anakinra-treated patients, a statistically significant 23% relative improvement, compared with no significant change in placebo patients. The KOOS activities of daily living subscore showed a similar pattern, falling by a statistically significant 10.5 points in the anakinra-treated group, a 46% relative improvement compared with baseline.

Prior results showed that a change of 8–10 points in this measure corresponded to a clinically significant change after reconstruction of the anterior cruciate ligament, Dr. Kraus said at the congress, sponsored by the Osteoarthritis Research Society International.

The total KOOS score improved by an average of 20 points in the drug-treated patients, a significant 24% relative improvement, compared with no significant change in the placebo patients.

The anakinra-treated patients also showed strong trends toward further improvements in total KOOS score and activity subscore when they underwent another assessment 14 days after their injection, while the placebo patients continued to show no substantial changes.

Major Finding: A single, 150-mg intra-articular injection of anakinra an average of 15 days after knee injury led to a statistically and clinically significant 10.5-point improvement in the KOOS activity of daily living score 4 days after injection. Patients receiving a placebo injection showed no significant improvement.

Data Source: Randomized, placebo-controlled pilot study with 11 patients.

Disclosures: Dr. Kraus's study did not have commercial funding. She said she had no relevant financial conflicts.

BRUSSELS — The clinical response seen to injection of a targeted anti-inflammatory drug into an acutely damaged knee joint within a few weeks of injury in a controlled pilot study with 11 patients provided a step toward the development of a new approach to treating traumatic joint injury.

“We should start to treat joint injury much more emergently, like an acute myocardial infarction.” Acute joint injury “is a critical event where early intervention might improve long-term outcome,” including heading off the eventual development of osteoarthritis, Dr. Virginia Byers Kraus said at the meeting.

“Blocking sterile inflammation early in acute, joint injury may be a means to stop development of chronic tissue injury and post-traumatic osteoarthritis,” said Dr. Kraus, professor of medicine at Duke University in Durham, N.C. “The early phase of acute joint injury represents a window of opportunity for providing treatment to promote healing and to prevent a subsequent cascade of joint destructive processes.

The study enrolled 11 patients younger than 40 within the first month following an MRI-confirmed tear of their anterior cruciate ligament in one knee. Following randomization, six patients received a single, 150-mg intra-articular injection of anakinra, which is an interleukin-1 (IL-1) receptor antagonist that blocks the effects of IL-1, a primary proinflammatory cytokine. The other five patients received saline injections. Anakinra (Kineret) has U.S. approval for the treatment of rheumatoid arthritis by subcutaneous injection, but carries no approval for the treatment of osteoarthritis or for intra-articular injection.

The age of the 11 patients averaged 24 years (range, 18–29 years). They received their injections an average of 15 days after their injury (range, 6–27 days).

Four days after treatment, patients who received an anakinra injection had significant and clinically meaningful improvements in several measures on the Knee Injury and Osteoarthritis Outcome Score (KOOS), improvements not seen in placebo patients, she reported.

The KOOS pain subscore fell by an average of 3.8 points in anakinra-treated patients, a statistically significant 23% relative improvement, compared with no significant change in placebo patients. The KOOS activities of daily living subscore showed a similar pattern, falling by a statistically significant 10.5 points in the anakinra-treated group, a 46% relative improvement compared with baseline.

Prior results showed that a change of 8–10 points in this measure corresponded to a clinically significant change after reconstruction of the anterior cruciate ligament, Dr. Kraus said at the congress, sponsored by the Osteoarthritis Research Society International.

The total KOOS score improved by an average of 20 points in the drug-treated patients, a significant 24% relative improvement, compared with no significant change in the placebo patients.

The anakinra-treated patients also showed strong trends toward further improvements in total KOOS score and activity subscore when they underwent another assessment 14 days after their injection, while the placebo patients continued to show no substantial changes.

BRUSSELS — The use of magnetic resonance imaging may enable earlier recognition of knee osteoarthritis, and should be incorporated into recommended diagnostic criteria, a panel of 16 osteoarthritis experts concluded.

Using MRI to define knee osteoarthritis (OA) may allow detection of the disease before radiographic changes occur. But despite a growing body of literature on the role of MRI in OA, little uniformity exists for its diagnostic application, perhaps because of the absence of criteria for an MRI-based structural diagnosis of OA, the group said.

The Osteoarthritis Research Society International (OARSI) organized the 16-member panel, the OA Imaging Working Group, to develop an MRI-based definition of structural OA. The working group sought to identify structural changes on MRI that defined a structural diagnosis of knee OA, Dr. David J. Hunter and the other members of the working group wrote in a poster presented at the congress, which was organized by OARSI.

The working group began with a literature review through April 2009, a process that yielded 25 studies that met the group's inclusion criteria and evaluated MRI diagnostic performance. Through a multiphase process of discussion and voting, the group agreed on a set of nine propositions and two OA definitions based on MRI criteria. (See boxes.) These constitute “statements of preamble and context setting.” The two definitions “offer an opportunity for formal testing against other diagnostic constructs,” said Dr. Hunter of the University of Sydney and his associates in the working group.

The working group noted that the American College of Rheumatology in 1986 first released the current standard criteria for diagnosing OA, which deal only with radiographic imaging (Arthritis Rheum. 1986;29:1039–49). The European League Against Rheumatism published more current recommendations this year, but focused on a clinical diagnosis that did not involve imaging (Ann. Rheum. Dis. 2010;69:483–9).

The working group aimed to “include MRI as a means to define the disease with the intent that one may be able to identify early, pre-radiographic disease, thus enabling recruitment of study populations where structure modification (or structure maintenance) may be realistic in a more preventive manner.”

The group stressed that “the propositions have been developed for structural OA, not for a clinical diagnosis, not for early OA, and not to facilitate staging of the disease.”

An osteoarthritis specialist who was not involved with the working group cautioned that waiting for MRI structural changes that are specific for OA may still miss a truly early diagnosis, before irreversible pathology occurred.

“There are early changes [seen with MRI] that are not picked up on radiographs, but we don't yet have a standardized, validated definition of an earlier stage” on MRI, Dr. Tuhina Neogi, a rheumatologist at Boston University, said in an interview.

Dr. Hunter said that he has received research support from AstraZeneca, DJO Inc. (DonJoy), Eli Lilly & Co., Merck & Co., Pfizer Inc., Stryker Corp., and Wyeth. Eight of the other members of the working group also provided disclosures, whereas the remaining seven members said they had no disclosures. Dr. Neogi had no disclosures.

The OARSI Panel's Propositions

The following are nine propositions on MRI diagnosis of knee OA:

1. MRI changes of OA may occur in the absence of radiographic findings of OA.

2. MRI may add to the diagnosis and should be incorporated into the ACR diagnostic criteria including x-ray, clinical, and laboratory parameters.

3. MRI may be included in clinical studies according to the criteria detailed above, but should not be a primary diagnostic tool.

4. Certain MRI changes that occur in isolation are not diagnostic of OA. These include cartilage loss, change in cartilage composition, cystic change and development of bone marrow lesions, ligamentous and tendinous damage, meniscal damage, and effusion and synovitis.

5. No single finding is diagnostic of knee OA.

6. MRI findings indicative of knee OA may include abnormalities in all tissues of the joint (bone, cartilage, meniscus, synovium, ligament, and capsule).

7. Given the multiple tissue abnormalities detected by MRI in OA, diagnostic criteria are likely to involve several possible combinations of features.

8. Definite osteophyte production is indicative of OA.

9. Joint space narrowing as assessed by (nonweight-bearing) MRI cannot be used as a diagnostic criterion.

Two MRI-Based Definitions

The panel arrived at the following two definitions for MRI findings that were diagnostic of knee osteoarthritis:

1. Tibiofemoral OA should have either both features from group A (below), or one feature from group A and at least two features from group B. Examination of the patient must also rule out joint trauma within the last 6 months (by history) as well as inflammatory arthritis (diagnosed by radiographs, history, and laboratory findings).

▸ Group A: Definite osteophyte formation; full thickness cartilage loss.

▸ Group B: Subchondral marrow lesion or cyst not associated with meniscal or ligamentous attachments; meniscal subluxation, maceration, or degenerative (horizontal) tear; partial-thickness cartilage loss (without full thickness loss).

2. Patellofemoral OA requires the following features involving the patella or the anterior femur:

▸ Definite osteophyte formation.

▸ Partial- or full-thickness cartilage loss.

BRUSSELS — The use of magnetic resonance imaging may enable earlier recognition of knee osteoarthritis, and should be incorporated into recommended diagnostic criteria, a panel of 16 osteoarthritis experts concluded.

Using MRI to define knee osteoarthritis (OA) may allow detection of the disease before radiographic changes occur. But despite a growing body of literature on the role of MRI in OA, little uniformity exists for its diagnostic application, perhaps because of the absence of criteria for an MRI-based structural diagnosis of OA, the group said.

The Osteoarthritis Research Society International (OARSI) organized the 16-member panel, the OA Imaging Working Group, to develop an MRI-based definition of structural OA. The working group sought to identify structural changes on MRI that defined a structural diagnosis of knee OA, Dr. David J. Hunter and the other members of the working group wrote in a poster presented at the congress, which was organized by OARSI.

The working group began with a literature review through April 2009, a process that yielded 25 studies that met the group's inclusion criteria and evaluated MRI diagnostic performance. Through a multiphase process of discussion and voting, the group agreed on a set of nine propositions and two OA definitions based on MRI criteria. (See boxes.) These constitute “statements of preamble and context setting.” The two definitions “offer an opportunity for formal testing against other diagnostic constructs,” said Dr. Hunter of the University of Sydney and his associates in the working group.

The working group noted that the American College of Rheumatology in 1986 first released the current standard criteria for diagnosing OA, which deal only with radiographic imaging (Arthritis Rheum. 1986;29:1039–49). The European League Against Rheumatism published more current recommendations this year, but focused on a clinical diagnosis that did not involve imaging (Ann. Rheum. Dis. 2010;69:483–9).

The working group aimed to “include MRI as a means to define the disease with the intent that one may be able to identify early, pre-radiographic disease, thus enabling recruitment of study populations where structure modification (or structure maintenance) may be realistic in a more preventive manner.”

The group stressed that “the propositions have been developed for structural OA, not for a clinical diagnosis, not for early OA, and not to facilitate staging of the disease.”

An osteoarthritis specialist who was not involved with the working group cautioned that waiting for MRI structural changes that are specific for OA may still miss a truly early diagnosis, before irreversible pathology occurred.

“There are early changes [seen with MRI] that are not picked up on radiographs, but we don't yet have a standardized, validated definition of an earlier stage” on MRI, Dr. Tuhina Neogi, a rheumatologist at Boston University, said in an interview.

Dr. Hunter said that he has received research support from AstraZeneca, DJO Inc. (DonJoy), Eli Lilly & Co., Merck & Co., Pfizer Inc., Stryker Corp., and Wyeth. Eight of the other members of the working group also provided disclosures, whereas the remaining seven members said they had no disclosures. Dr. Neogi had no disclosures.

The OARSI Panel's Propositions

The following are nine propositions on MRI diagnosis of knee OA:

1. MRI changes of OA may occur in the absence of radiographic findings of OA.

2. MRI may add to the diagnosis and should be incorporated into the ACR diagnostic criteria including x-ray, clinical, and laboratory parameters.

3. MRI may be included in clinical studies according to the criteria detailed above, but should not be a primary diagnostic tool.

4. Certain MRI changes that occur in isolation are not diagnostic of OA. These include cartilage loss, change in cartilage composition, cystic change and development of bone marrow lesions, ligamentous and tendinous damage, meniscal damage, and effusion and synovitis.

5. No single finding is diagnostic of knee OA.

6. MRI findings indicative of knee OA may include abnormalities in all tissues of the joint (bone, cartilage, meniscus, synovium, ligament, and capsule).

7. Given the multiple tissue abnormalities detected by MRI in OA, diagnostic criteria are likely to involve several possible combinations of features.

8. Definite osteophyte production is indicative of OA.

9. Joint space narrowing as assessed by (nonweight-bearing) MRI cannot be used as a diagnostic criterion.

Two MRI-Based Definitions

The panel arrived at the following two definitions for MRI findings that were diagnostic of knee osteoarthritis:

1. Tibiofemoral OA should have either both features from group A (below), or one feature from group A and at least two features from group B. Examination of the patient must also rule out joint trauma within the last 6 months (by history) as well as inflammatory arthritis (diagnosed by radiographs, history, and laboratory findings).

▸ Group A: Definite osteophyte formation; full thickness cartilage loss.

▸ Group B: Subchondral marrow lesion or cyst not associated with meniscal or ligamentous attachments; meniscal subluxation, maceration, or degenerative (horizontal) tear; partial-thickness cartilage loss (without full thickness loss).

2. Patellofemoral OA requires the following features involving the patella or the anterior femur:

▸ Definite osteophyte formation.

▸ Partial- or full-thickness cartilage loss.

BRUSSELS — The use of magnetic resonance imaging may enable earlier recognition of knee osteoarthritis, and should be incorporated into recommended diagnostic criteria, a panel of 16 osteoarthritis experts concluded.

Using MRI to define knee osteoarthritis (OA) may allow detection of the disease before radiographic changes occur. But despite a growing body of literature on the role of MRI in OA, little uniformity exists for its diagnostic application, perhaps because of the absence of criteria for an MRI-based structural diagnosis of OA, the group said.

The Osteoarthritis Research Society International (OARSI) organized the 16-member panel, the OA Imaging Working Group, to develop an MRI-based definition of structural OA. The working group sought to identify structural changes on MRI that defined a structural diagnosis of knee OA, Dr. David J. Hunter and the other members of the working group wrote in a poster presented at the congress, which was organized by OARSI.

The working group began with a literature review through April 2009, a process that yielded 25 studies that met the group's inclusion criteria and evaluated MRI diagnostic performance. Through a multiphase process of discussion and voting, the group agreed on a set of nine propositions and two OA definitions based on MRI criteria. (See boxes.) These constitute “statements of preamble and context setting.” The two definitions “offer an opportunity for formal testing against other diagnostic constructs,” said Dr. Hunter of the University of Sydney and his associates in the working group.

The working group noted that the American College of Rheumatology in 1986 first released the current standard criteria for diagnosing OA, which deal only with radiographic imaging (Arthritis Rheum. 1986;29:1039–49). The European League Against Rheumatism published more current recommendations this year, but focused on a clinical diagnosis that did not involve imaging (Ann. Rheum. Dis. 2010;69:483–9).

The working group aimed to “include MRI as a means to define the disease with the intent that one may be able to identify early, pre-radiographic disease, thus enabling recruitment of study populations where structure modification (or structure maintenance) may be realistic in a more preventive manner.”

The group stressed that “the propositions have been developed for structural OA, not for a clinical diagnosis, not for early OA, and not to facilitate staging of the disease.”

An osteoarthritis specialist who was not involved with the working group cautioned that waiting for MRI structural changes that are specific for OA may still miss a truly early diagnosis, before irreversible pathology occurred.

“There are early changes [seen with MRI] that are not picked up on radiographs, but we don't yet have a standardized, validated definition of an earlier stage” on MRI, Dr. Tuhina Neogi, a rheumatologist at Boston University, said in an interview.

Dr. Hunter said that he has received research support from AstraZeneca, DJO Inc. (DonJoy), Eli Lilly & Co., Merck & Co., Pfizer Inc., Stryker Corp., and Wyeth. Eight of the other members of the working group also provided disclosures, whereas the remaining seven members said they had no disclosures. Dr. Neogi had no disclosures.

The OARSI Panel's Propositions

The following are nine propositions on MRI diagnosis of knee OA:

1. MRI changes of OA may occur in the absence of radiographic findings of OA.

2. MRI may add to the diagnosis and should be incorporated into the ACR diagnostic criteria including x-ray, clinical, and laboratory parameters.

3. MRI may be included in clinical studies according to the criteria detailed above, but should not be a primary diagnostic tool.

4. Certain MRI changes that occur in isolation are not diagnostic of OA. These include cartilage loss, change in cartilage composition, cystic change and development of bone marrow lesions, ligamentous and tendinous damage, meniscal damage, and effusion and synovitis.

5. No single finding is diagnostic of knee OA.

6. MRI findings indicative of knee OA may include abnormalities in all tissues of the joint (bone, cartilage, meniscus, synovium, ligament, and capsule).

7. Given the multiple tissue abnormalities detected by MRI in OA, diagnostic criteria are likely to involve several possible combinations of features.

8. Definite osteophyte production is indicative of OA.

9. Joint space narrowing as assessed by (nonweight-bearing) MRI cannot be used as a diagnostic criterion.

Two MRI-Based Definitions

The panel arrived at the following two definitions for MRI findings that were diagnostic of knee osteoarthritis:

1. Tibiofemoral OA should have either both features from group A (below), or one feature from group A and at least two features from group B. Examination of the patient must also rule out joint trauma within the last 6 months (by history) as well as inflammatory arthritis (diagnosed by radiographs, history, and laboratory findings).

▸ Group A: Definite osteophyte formation; full thickness cartilage loss.

▸ Group B: Subchondral marrow lesion or cyst not associated with meniscal or ligamentous attachments; meniscal subluxation, maceration, or degenerative (horizontal) tear; partial-thickness cartilage loss (without full thickness loss).

2. Patellofemoral OA requires the following features involving the patella or the anterior femur:

▸ Definite osteophyte formation.

▸ Partial- or full-thickness cartilage loss.

TORONTO — Women aged 67 years or older with a bone mineral density T score higher than −1.50 on dual-energy x-ray absorptiometry can have their next DXA examination deferred for at least 10 years with a low risk that they'll progress to osteoporosis in the interim, according to an analysis of data from more than 5,000 U.S. women.

“Fewer than 10% of women with a BMD [bone mineral density] T score of more than −1.50 were estimated to transition to osteoporosis if followed for 15 years,” Dr. Margaret L. Gourlay said.

For these women, “repeat testing before 10 years is unlikely to show osteoporosis,” she said, and for women with a T score of −1.50 to −1.99, “a 5-year interval could be considered.”

The results provide the first evidence-based guidance available on the appropriate interval for osteoporosis screening in elderly women.

“The value of these results is that we can be less concerned about women with good BMD,” Dr. Gourlay said in an interview. “We don't need to go on autopilot and screen [all women] every 2 years.”

Medicare reimburses for screening women aged 65 years or older with dual-energy x-ray absorptiometry (DXA) every 2 years, she noted, and hence U.S. physicians often recommend this screening interval.

Earlier this year, however, an updated review of osteoporosis screening by the U.S. Preventive Services Task Force (USPSTF) noted that no evidence existed to support any screening interval (Ann. Intern. Med. 2010;153:99–111).

The results “were a surprise in a good way,” said Dr. Gourlay, a family physician at the University of North Carolina in Chapel Hill. “This is good news for women with good BMD. For women with higher bone density, we're probably doing some unnecessary testing.”

The new results also showed that the T score exerted the strongest influence on the osteoporosis screening interval, more so than clinical risk factors for fracture. Adjustment for “risk factors did not make too much of a difference, so physicians do not need to make a FRAX calculation” to decide a screening interval, she said. “They can just go by the BMD.”

“With FRAX [the World Health Organization's Fracture Risk Assessment Tool] you don't just look at BMD, but primary care physicians can't stop [in the middle of a patient consultation] to calculate a FRAX score,” Dr. Gourlay said.

“When a patient has a BMD result in the good range, the main value of the new results is that we can be less concerned about these women” and the need for rescreening in the near future, she noted.

“The importance [of the new findings] is not the absolute time estimates we found; it's the magnitude of the difference.

A 16-year interval [for 10% of women to develop osteoporosis] for women in the top two T score groups, and a 5-year interval [for women with a baseline T score of −1.50 to −1.99] is quite different” from the way most physicians practice today, she said.

She cautioned that the finding needs confirmation from similar analyses using different data sets, and that it remains up to health policy-setting groups, such as the USPSTF, to consider the findings and use them to formulate updated screening recommendations. But, she added, the findings have already influenced her own approach to handling screening intervals.

“If I have a patient who missed a test and her prior T score was more than −1.50, I'm not nearly as worried now,” said Dr. Gourlay.

The analysis used data collected in the Study of Osteoporotic Fractures (SOF), which enrolled women aged 65 years or older in four U.S. cities starting in 1986 and has followed them since then.

Dr. Gourlay and her associates focused on 5,036 women in the study who underwent at least two serial BMD measures over a total of 15 years. Patients were excluded from analysis if they had osteoporosis at any hip site at baseline, had an incident hip fracture, or were treated with a bisphosphonate or calcitonin. Patients also were excluded if they died or dropped out of the study.

The analysis included 1,275 women who had at least one normal baseline BMD value (a T score of −1.00 or greater) and 4,279 women with at least one T score that identified them as having osteopenia (−1.01 to −2.49).

Some women fell into both categories if they underwent at least three DXA examinations starting with at least one normal T score followed by at least one osteopenic score.

At baseline, the rate of estrogen use ran 25% in women with a normal T score at baseline and 16% in women with osteopenia – relatively high rates by today's standards but typical for practice in the 1980s.

During follow-up, full transition to osteoporosis occurred in fewer than 1% of the participants with a T score of at least −1.00 at baseline, fewer than 5% of those with a T score of −1.01 to −1.49 at baseline, and 22% of women with a score of −1.50 to −1.99 at baseline. Transition to osteoporosis took place in 65% of women who had a T score of −2.00 to −2.49 at baseline.

After Dr. Gourlay and her associates adjusted for the covariates of age and continuous bone mineral density, they found that it took an estimated 16 years for 10% of women with a T score of −1.00 or higher at baseline to transition to osteoporosis.

The other three T score subgroups that were analyzed underwent covariate adjustment for age, body mass index, current estrogen use, any fracture after age 50, current smoking, and oral glucocorticoid use.

After adjustment, the average time for 10% of women to transition to osteoporosis was found to be 15.5 years in women following a T score measure of −1.01 to −1.49, 4.5 years in women with a T score of −1.50 to −1.99, and 1.2 years in women with a T score of −2.00 to −2.49.

The investigators performed an additional analysis that stratified women by their age at the baseline DXA examination.

Even among women who were 85 years old, it took an average of nearly 11 years for 10% to develop osteoporosis following a baseline T score of −1.01 to −1.49.

Dr. Gourlay said that she had no disclosures relevant to this study.

Source Elsevier Global Medical News

X-ray of the hip shows a fracture due to osteoporosis in an elderly woman. Less frequent screening may be indicated.

Source ©2010 Science Photo Library

TORONTO — Women aged 67 years or older with a bone mineral density T score higher than −1.50 on dual-energy x-ray absorptiometry can have their next DXA examination deferred for at least 10 years with a low risk that they'll progress to osteoporosis in the interim, according to an analysis of data from more than 5,000 U.S. women.

“Fewer than 10% of women with a BMD [bone mineral density] T score of more than −1.50 were estimated to transition to osteoporosis if followed for 15 years,” Dr. Margaret L. Gourlay said.

For these women, “repeat testing before 10 years is unlikely to show osteoporosis,” she said, and for women with a T score of −1.50 to −1.99, “a 5-year interval could be considered.”

The results provide the first evidence-based guidance available on the appropriate interval for osteoporosis screening in elderly women.

“The value of these results is that we can be less concerned about women with good BMD,” Dr. Gourlay said in an interview. “We don't need to go on autopilot and screen [all women] every 2 years.”

Medicare reimburses for screening women aged 65 years or older with dual-energy x-ray absorptiometry (DXA) every 2 years, she noted, and hence U.S. physicians often recommend this screening interval.

Earlier this year, however, an updated review of osteoporosis screening by the U.S. Preventive Services Task Force (USPSTF) noted that no evidence existed to support any screening interval (Ann. Intern. Med. 2010;153:99–111).

The results “were a surprise in a good way,” said Dr. Gourlay, a family physician at the University of North Carolina in Chapel Hill. “This is good news for women with good BMD. For women with higher bone density, we're probably doing some unnecessary testing.”

The new results also showed that the T score exerted the strongest influence on the osteoporosis screening interval, more so than clinical risk factors for fracture. Adjustment for “risk factors did not make too much of a difference, so physicians do not need to make a FRAX calculation” to decide a screening interval, she said. “They can just go by the BMD.”

“With FRAX [the World Health Organization's Fracture Risk Assessment Tool] you don't just look at BMD, but primary care physicians can't stop [in the middle of a patient consultation] to calculate a FRAX score,” Dr. Gourlay said.

“When a patient has a BMD result in the good range, the main value of the new results is that we can be less concerned about these women” and the need for rescreening in the near future, she noted.

“The importance [of the new findings] is not the absolute time estimates we found; it's the magnitude of the difference.

A 16-year interval [for 10% of women to develop osteoporosis] for women in the top two T score groups, and a 5-year interval [for women with a baseline T score of −1.50 to −1.99] is quite different” from the way most physicians practice today, she said.

She cautioned that the finding needs confirmation from similar analyses using different data sets, and that it remains up to health policy-setting groups, such as the USPSTF, to consider the findings and use them to formulate updated screening recommendations. But, she added, the findings have already influenced her own approach to handling screening intervals.

“If I have a patient who missed a test and her prior T score was more than −1.50, I'm not nearly as worried now,” said Dr. Gourlay.

The analysis used data collected in the Study of Osteoporotic Fractures (SOF), which enrolled women aged 65 years or older in four U.S. cities starting in 1986 and has followed them since then.

Dr. Gourlay and her associates focused on 5,036 women in the study who underwent at least two serial BMD measures over a total of 15 years. Patients were excluded from analysis if they had osteoporosis at any hip site at baseline, had an incident hip fracture, or were treated with a bisphosphonate or calcitonin. Patients also were excluded if they died or dropped out of the study.

The analysis included 1,275 women who had at least one normal baseline BMD value (a T score of −1.00 or greater) and 4,279 women with at least one T score that identified them as having osteopenia (−1.01 to −2.49).

Some women fell into both categories if they underwent at least three DXA examinations starting with at least one normal T score followed by at least one osteopenic score.

At baseline, the rate of estrogen use ran 25% in women with a normal T score at baseline and 16% in women with osteopenia – relatively high rates by today's standards but typical for practice in the 1980s.

During follow-up, full transition to osteoporosis occurred in fewer than 1% of the participants with a T score of at least −1.00 at baseline, fewer than 5% of those with a T score of −1.01 to −1.49 at baseline, and 22% of women with a score of −1.50 to −1.99 at baseline. Transition to osteoporosis took place in 65% of women who had a T score of −2.00 to −2.49 at baseline.

After Dr. Gourlay and her associates adjusted for the covariates of age and continuous bone mineral density, they found that it took an estimated 16 years for 10% of women with a T score of −1.00 or higher at baseline to transition to osteoporosis.

The other three T score subgroups that were analyzed underwent covariate adjustment for age, body mass index, current estrogen use, any fracture after age 50, current smoking, and oral glucocorticoid use.

After adjustment, the average time for 10% of women to transition to osteoporosis was found to be 15.5 years in women following a T score measure of −1.01 to −1.49, 4.5 years in women with a T score of −1.50 to −1.99, and 1.2 years in women with a T score of −2.00 to −2.49.

The investigators performed an additional analysis that stratified women by their age at the baseline DXA examination.

Even among women who were 85 years old, it took an average of nearly 11 years for 10% to develop osteoporosis following a baseline T score of −1.01 to −1.49.

Dr. Gourlay said that she had no disclosures relevant to this study.

Source Elsevier Global Medical News

X-ray of the hip shows a fracture due to osteoporosis in an elderly woman. Less frequent screening may be indicated.

Source ©2010 Science Photo Library

TORONTO — Women aged 67 years or older with a bone mineral density T score higher than −1.50 on dual-energy x-ray absorptiometry can have their next DXA examination deferred for at least 10 years with a low risk that they'll progress to osteoporosis in the interim, according to an analysis of data from more than 5,000 U.S. women.

“Fewer than 10% of women with a BMD [bone mineral density] T score of more than −1.50 were estimated to transition to osteoporosis if followed for 15 years,” Dr. Margaret L. Gourlay said.

For these women, “repeat testing before 10 years is unlikely to show osteoporosis,” she said, and for women with a T score of −1.50 to −1.99, “a 5-year interval could be considered.”

The results provide the first evidence-based guidance available on the appropriate interval for osteoporosis screening in elderly women.

“The value of these results is that we can be less concerned about women with good BMD,” Dr. Gourlay said in an interview. “We don't need to go on autopilot and screen [all women] every 2 years.”

Medicare reimburses for screening women aged 65 years or older with dual-energy x-ray absorptiometry (DXA) every 2 years, she noted, and hence U.S. physicians often recommend this screening interval.

Earlier this year, however, an updated review of osteoporosis screening by the U.S. Preventive Services Task Force (USPSTF) noted that no evidence existed to support any screening interval (Ann. Intern. Med. 2010;153:99–111).

The results “were a surprise in a good way,” said Dr. Gourlay, a family physician at the University of North Carolina in Chapel Hill. “This is good news for women with good BMD. For women with higher bone density, we're probably doing some unnecessary testing.”

The new results also showed that the T score exerted the strongest influence on the osteoporosis screening interval, more so than clinical risk factors for fracture. Adjustment for “risk factors did not make too much of a difference, so physicians do not need to make a FRAX calculation” to decide a screening interval, she said. “They can just go by the BMD.”

“With FRAX [the World Health Organization's Fracture Risk Assessment Tool] you don't just look at BMD, but primary care physicians can't stop [in the middle of a patient consultation] to calculate a FRAX score,” Dr. Gourlay said.

“When a patient has a BMD result in the good range, the main value of the new results is that we can be less concerned about these women” and the need for rescreening in the near future, she noted.

“The importance [of the new findings] is not the absolute time estimates we found; it's the magnitude of the difference.

A 16-year interval [for 10% of women to develop osteoporosis] for women in the top two T score groups, and a 5-year interval [for women with a baseline T score of −1.50 to −1.99] is quite different” from the way most physicians practice today, she said.

She cautioned that the finding needs confirmation from similar analyses using different data sets, and that it remains up to health policy-setting groups, such as the USPSTF, to consider the findings and use them to formulate updated screening recommendations. But, she added, the findings have already influenced her own approach to handling screening intervals.

“If I have a patient who missed a test and her prior T score was more than −1.50, I'm not nearly as worried now,” said Dr. Gourlay.

The analysis used data collected in the Study of Osteoporotic Fractures (SOF), which enrolled women aged 65 years or older in four U.S. cities starting in 1986 and has followed them since then.

Dr. Gourlay and her associates focused on 5,036 women in the study who underwent at least two serial BMD measures over a total of 15 years. Patients were excluded from analysis if they had osteoporosis at any hip site at baseline, had an incident hip fracture, or were treated with a bisphosphonate or calcitonin. Patients also were excluded if they died or dropped out of the study.

The analysis included 1,275 women who had at least one normal baseline BMD value (a T score of −1.00 or greater) and 4,279 women with at least one T score that identified them as having osteopenia (−1.01 to −2.49).

Some women fell into both categories if they underwent at least three DXA examinations starting with at least one normal T score followed by at least one osteopenic score.

At baseline, the rate of estrogen use ran 25% in women with a normal T score at baseline and 16% in women with osteopenia – relatively high rates by today's standards but typical for practice in the 1980s.

During follow-up, full transition to osteoporosis occurred in fewer than 1% of the participants with a T score of at least −1.00 at baseline, fewer than 5% of those with a T score of −1.01 to −1.49 at baseline, and 22% of women with a score of −1.50 to −1.99 at baseline. Transition to osteoporosis took place in 65% of women who had a T score of −2.00 to −2.49 at baseline.

After Dr. Gourlay and her associates adjusted for the covariates of age and continuous bone mineral density, they found that it took an estimated 16 years for 10% of women with a T score of −1.00 or higher at baseline to transition to osteoporosis.

The other three T score subgroups that were analyzed underwent covariate adjustment for age, body mass index, current estrogen use, any fracture after age 50, current smoking, and oral glucocorticoid use.

After adjustment, the average time for 10% of women to transition to osteoporosis was found to be 15.5 years in women following a T score measure of −1.01 to −1.49, 4.5 years in women with a T score of −1.50 to −1.99, and 1.2 years in women with a T score of −2.00 to −2.49.

The investigators performed an additional analysis that stratified women by their age at the baseline DXA examination.

Even among women who were 85 years old, it took an average of nearly 11 years for 10% to develop osteoporosis following a baseline T score of −1.01 to −1.49.

Dr. Gourlay said that she had no disclosures relevant to this study.

Source Elsevier Global Medical News

X-ray of the hip shows a fracture due to osteoporosis in an elderly woman. Less frequent screening may be indicated.

Source ©2010 Science Photo Library