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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, thus 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 different source reviews that examined the three medicines that have been tested in randomized trials.

The bisphosphonates did not appreciably reduce fractures among women who had not had a previous fracture and those with relatively normal bone density. 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 bisphosphonates do appear to reduce fractures among women with very low BMD and those who have had previous fractures, and should be considered. However in those without very low BMD or fractures no study has demonstrated a true benefit. In the Cochrane review of alendronate the authors suggest a benefit in the reduction of vertebral fractures based on the results of a single study.4 However this finding is based on a subgroup analysis of a group subjected to a post-hoc change in the BMD cut offs for primary versus secondary. Moreover, the clinical significance of vertebral fractures in this study (and others) is unclear, as these were typically detected radiographically (by routine screening x-rays of the spine) rather than clinically. Thus it is not at all obvious that these are patient-important measures.

Author

David Newman, MD

Published/Updated

May 16, 2011