Source: Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, Coyle D, Tugwell P. Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD003376.
Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, Coyle D, Tugwell P. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001155.
Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Welch V, Coyle D, Tugwell P. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD004523.
Efficacy Endpoints: Fracture prevention
Harm Endpoints: Atypical fractures, jaw osteonecrosis, GI and musculoskeletal side effects (harms are uncommon but do clearly occur and are not well-studied)
Narrative: The bisphophonates (etidronate, alendronate, risedronate) are anti-resorptive medicines that block the resorptive action in bone, increasing the density of the bone in some areas. Bone construction and resorption are complex processes and the increase in bone density that the bisphosphonates are able to effect leads to a complicated cascade of hormonal and muscuoskeletal effects. Ideally this will lead to increased bone strength and fewer fractures. This summary and review is a combination of three source Cochrane reviews that examined three bisphosphonate medicines that have been tested in randomized trials.
The medicines reduced fractures. Their greatest impact was on the rate of vertebral fractures, but they also demonstrated statistically demonstrable benefits in the reduction of dreaded hip fractures, and also wrist fractures. Typically for every 100 women taking the medicines six avoided a fracture of some sort over three years of therapy. Particularly based on the one hip fracture that is avoided per 100 women this benefit may be highly important in terms of reducing morbidity or disability.
It is important to recall that the harms of bisphosophonates are increasingly an object of study and speculation, particularly now that the drugs have been on the market for some time and their long term use has become more common. Virtually none of the initial studies examining the drugs included treatment for more than three to five years, however serious side effects such as atypical fractures1 and osteonecrosis of the jaw2 and gastrointestinal, musculoskeletal, and other side effects leading to disproportionate discontinuation3 have been increasingly linked to use of these drugs in the long term. These side effects should strike a note of caution, and should firstly be discussed with any woman considering bisphosphonate therapy, and secondly be a warning against initiating this therapy in patient groups who have not been proven to benefit (i.e. women with very low bone mineral density and women with a history of fractures).
Caveats: The majority of the benefit to the bisphosphonates is seen in vertebral fracture reduction, an outcome that is often made by screening radiographs rather than clinically. In other words it is not clear that it would be important to prevent subclinical vertebral fractures, nor is it clear that reducing this outcome represents an aggregate benefit when one considers the adverse effects of the medicines. However a reduction in hip fractures, even at 1 per 100, may represent a potentially important public health measure. Thus it would be helpful to have large scale population-based studies determine whether or not there are overall increases in longevity or decreases in disability with the bisphosphonates.
Finally, the studies examined in the Cochrane reviews are industry sponsored. A long history of selective outcome reporting,4 selective publication,5,6 occasionally fraudulent reporting,7,8 and dubious methodologic choices9 all indicate that there is reason to scrutinize and doubt the optimistic claims of these data. Thus these results, while adequate for making clinical decisions, should be considered preliminary unless and until they can be verified on a large scale by parties without a financial stake in the results.
Author: David Newman, MD
Published/Updated: May 16, 2011
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