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AAOS: Osteoporosis Drugs May Weaken Bones in Long Term
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NEW ORLEANS -- The gains bisphosphonate use brings in the structural integrity of the femur decay over time in postmenopausal women with osteoporosis, researchers found.
In women who took oral bisphosphonates for four to five years, buckling ratio, a measure of structural integrity, improved significantly in the proximal femur from baseline, according to Anthony Ding, a medical student at Columbia University College of Physicians and Surgeons in New York City.
However, those improvements started to erode and creep back toward pretreatment levels when bisphosphonate use lasted more than five years, he reported at the American Academy of Orthopaedic Surgeons meeting here.
This effect might provide an explanation for recent reports linking long-term bisphosphonate use with atypical transverse subtrochanteric fractures, Ding said.
These fractures do not behave like typical subtrochanteric fractures, he said, and usually occur with little or no trauma, are slow to heal, and are associated with prolonged disability, he said.
Although some case reports have identified an apparent association between long-term bisphosphonate use and these atypical fractures, the FDA announced yesterday that there did not, in fact, appear to be good evidence of such a link.
The agency said it would continue to investigate the possibility.
The Endocrine Society sided with the FDA.
"Although these news reports have generated concern among patients and healthcare providers, there is currently no conclusive evidence demonstrating that bisphosphonates cause this rare type of fracture," a statement read.
The organization advised patients to discuss the risks and benefits of continuing bisophosphonate treatment and to continue taking the drugs unless their physician directs them to stop.
"For most patients," the statement continued, "the benefits of therapy in leading to osteoporotic fracture reduction will outweigh the potential risks of developing this rare type of femur fracture."
At least one orthopedic surgeon, however, is convinced that the risk is real.
Lisa Cannada, MD, of St. Louis University, said that Ding’s study and others coming to similar conclusions "are convincing that the bone architecture is affected [with long-term use]."
She said that the risk likely results from because bisphosphonates prevent normal bone remodeling with everyday wear and tear.
"If women can’t respond to the stresses, or adapt to them, because their bones can’t turn over, that's when you have the problems," she explained.
The short-term benefits of bisphosphonates are well established, she added, but future strategies might involve switching women to supplementation with calcium and vitamin D or another agent after about four or five years of using the osteoporosis medications.
"Bisphosphonates definitely have a place in the short term but it appears from this, not in the long term," she said.
Ding and his co-author, Melvin Rosenwasser, MD, also of Columbia, wanted to explore the structural effects of bisphosphonate treatment and to determine whether there were differences between short- and long-term use.
They performed a retrospective cohort study of 111 postmenopausal women with osteoporosis -- 61 who had been taking oral bisphosphonates for at least four years and 50 controls who were taking calcium and vitamin D supplementation only.
Women with comorbidities affecting bone metabolism and those with secondary causes of osteoporosis were excluded.
All women had serial dual x-ray absorptiometry (DXA) scans of the proximal femur that were analyzed using the Hip Structural Analysis program, a validated tool looking at the mineral distribution in the scans.
Section modulus, a measure of bending strength, was improved from baseline in both the short- and long-term bisphosphonate users. There was no difference between groups (P=0.63).
The results were similar for measures of axial strength, with no differences based on length of bisphosphonate treatment.
However, for buckling ratio, which measures the likelihood that the cortex will collapse and fail, there were significantly greater improvements in the short-term group (P=0.02).
In the short-term group, the buckling ratio improved 3.8% from baseline, whereas in the long-term group, the gains were attenuated to just 1.3% from baseline (P=0.02).
"Interestingly, the phase in which it decays corresponds to all these reports when these [atypical] fractures occur," Ding said.
The control group declined on all measures.
Ding said tools like the Hip Structural Analysis program may be used to help identify patients at risk for atypical subtrochanteric fractures and allow for adjustments in bisphosphonate dosing to maximize benefits and minimize risk.
Action Points
<LI class=APP>Explain to interested patients that this study did not examine rates of atypical subtrochanteric fractures in relation to the observed effects from bisphosphonate use on structural integrity in the femur.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
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发表于 2010-5-20 22:11:57
