Men's Osteoporosis Support GroupAtypical Fractures of the Femoral Diaphysis in Postmenopausal Women Taking Alendronate Letter to the Editor, Volume 358:1304-1306, March 20, 2008, Number 12, NEMJ. Lenart BA and others. The authors report on 15 women who suffered unusual femoral fractures while on long-term alendronate (Fosamax) therapy. They note that two previous studies have also described individuals on long-term alendronate therapy (combined with or without other medications that might also affect bone turnover) who had unusual fractures and suggest this may be related to severely suppressed bone turnover (SSBT). Bone is a dynamic tissue that is constantly turning over. That is, older bone is removed by cells called osteoclasts and is reformed and renewed by cells call osteoblasts. This keeps the bone healthy and strong. In osteoporosis there is a problem with the normal bone turnover/bone formation equilibrium in which too much bone turns over causing a weakening in bone with lower than normal density as bone formation can't keep up with the rate of bone turnover. The bisphosphonates (Fosamax, Actonel, Boniva) are often given to treat osteoporosis because they act to prevent bone turnover which leads to a net buildup of new bone. However, it has been shown that Fosamax can reduce bone turnover by as much as 90-95%, this while biochemical markers of bone turnover may only show about 50% reduction in turnover. It has been suggested that this severe reduction in bone turnover might lead to bone weakness because the microdamage that occurs continually as bone ages might not be replaced by new healthy bone in the presences of SSBT. SSBT is also implicated in bisphosphonate-induced osteonecrosis of the jaws (BIONJ) which has been discussed in several recent Updates. The authors are cognizant that their report isn't a controlled clinical trial, and shouldn't be taken a such. But they are recommending that prospective studies be performed to shed light on the importance of SSBT and the risk of atypical fractures in people taking long term bisphosphonates for osteoporosis. Editor's comments: These 15 cases are suggestive of another potential problem for those of us taking long-term bisphosphonates such as Fosamax. There appears to be a subgroup of individuals whose bone turnover is severely depressed, especially during long-term bisphosphonate therapy, and who are thus at increased risk of BIONJ or atypical low trauma fractures. The problem is how to identify those individuals with SSBT before they develop a problem. This is particularly true if biochemical markers of bone turnover don't reveal the depth of SSBT, which can be the case. The Marx and others article on BIONJ showed that fasting serum CTX was a quite reliable marker for suppression of bone turnover. Lenart and others hadn't used that test in their 15 cases which would have been informative, nor was it used in the two other articles cited in Lenart's letter to the editor. It would be helpful if future studies include the fasting serum CTX test when trying to determine the degree of SSBT, either to show that it is indeed helpful, or to show that we can disregard it and look for a more predictable test. Since a previous study has shown that stopping alendronate for five years didn't result in increased fracture rates compared to individuals who continued therapy, it appears that after five or more years on of bisphosphonate use, a one- or two-year drug holiday from the bisphosphonates might be warranted and beneficial to eliminate some of the atypical fracture risks cited in the Lenart and others letter and the other articles I referred to here. Unfortunately it might be several years before clinical trials prove the effectiveness of such a method, which for many of us means we'll never know exactly what to do. My suggestion is to discuss the options with your care provider and act according to your concern and the best science we have at this time. It is important to keep the numbers of individuals who have suffered these atypical fractures in proper perspective. The Lenart and others letter discusses 15 women, plus the other two articles mentioned in that letter discuss 22 more atypical fracture patients, for a total of 37 patients in over 12 years of Fosamax use as an FDA-approved medication. Thus the risk of an atypical fracture is quite low, but still something you would prefer to avoid if there are effective, proven ways to do that. I hope future research will center on finding which individuals respond to bisphosphonate therapy with SSBT. If there were an effective way to know in advance which individuals will have the greatest degree of bone turnover suppression that would really be beneficial since those individuals could be targeted for lower or less frequent doses of bisphosphonates, use of non-bisphosphonates therapy, drug holidays, or other means of reducing the degree of bone turnover suppression.
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