When do bisphosphonates make the most sense? A cochrane musculoskeletal group review: should you prescribe bisphosphonates for postmenopausal patients for primary as well as secondary prevention of osteoporotic fractures? Here's what the evidence tells us

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Authors: Tania Winzenberg and Graeme Jones
Date: Jan. 2011
From: Journal of Family Practice(Vol. 60, Issue 1)
Publisher: Jobson Medical Information LLC
Document Type: Report
Length: 4,733 words

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An estimated 10 million US residents, most of them women over the age of 50, suffer from osteoporosis, and another 33 million have low bone mass. (1) Together, they incur more than 2 million osteoporotic fractures annually. (1,2) In addition to the high cost of a single osteoporotic fracture in terms of morbidity, mortality, and health care spending, individuals who sustain one such fracture are at high risk for another. That risk can be greatly reduced with appropriate treatment.

Bisphosphonates, which act on osteoclasts to inhibit bone resorption, are first-line therapy for prevention of osteoporotic fractures. Four bisphosphonates--alendronate, ibandronate, risedronate, and zoledronic acid--are approved by the US Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis.

While menopause itself increases a woman's risk for osteoporotic fracture, questions remain about when to initiate preventive therapy, which patients are candidates for bisphosphonates, and whether bisphosphonates are effective for primary as well as secondary prevention. This overview from the Cochrane Musculoskeletal Group (CMSG) addresses those questions.

To help you provide optimal treatment for postmenopausal patients, we present the findings of recently conducted systematic reviews of 2 bisphosphonates--alendronate and risedronate--from the Cochrane Database of Systematic Reviews, (3,4) in context with the available evidence on the efficacy of ibandronate and zoledronic acid. Cochrane reviews of ibandronate and zoledronic acid are underway, but not yet completed. (5,6)

Alendronate reduces vertebral fracture risk across the board

Wells et al identified 11 RCTs for the alendronate review (3 primary and 8 secondary prevention trials), representing a total of 12,068 women. (3) (For definitions of what constituted a primary vs a secondary prevention trial, see the box on page 20.)

Doses of alendronate ranged from 1 to 20 mg daily, with most studies using doses of 5 or 10 mg. Treatment duration ranged from 1 to 4 years.

A look at the relative risk (RR) for primary and secondary prevention at different fracture sites (TABLE 1) highlights similarities and differences. The risk reduction for vertebral fractures was statistically significant--and about the same--for women being treated with alendronate for primary and secondary prevention (RR=0.55; 95% confidence interval [CI], 0.38-0.80; RR=0.55; 95% CI, 0.43-0.69, respectively). For all other (nonvertebral) fractures in patients being treated with alendronate, only the outcomes for secondary prevention were statistically significant.

Risedronate is effective only for secondary prevention

Seven RCTs, including 2 primary and 5 secondary prevention trials, were included in the Cochrane review of risedronate, representing a total of 14,049 women. (4) Doses ranged from 2.5 to 5 mg daily, but also included cyclical dosing--for example, taking 5 mg/d for the first 2 weeks of every month. Treatment duration ranged from 2 to 3 years.

At doses of 5 mg/d, there were no statistically significant decreases in fracture risk at any site in the primary prevention trials (TABLE 1), although the quality of evidence assessed was low. For secondary prevention, however, the risk reduction for vertebral fracture was significant (RR=0.61; 95% CI, 0.50-0.76), as were the reductions in risk for nonvertebral and hip fractures....

Source Citation

Source Citation
Winzenberg, Tania, and Graeme Jones. "When do bisphosphonates make the most sense? A cochrane musculoskeletal group review: should you prescribe bisphosphonates for postmenopausal patients for primary as well as secondary prevention of osteoporotic fractures? Here's what the evidence tells us." Journal of Family Practice, vol. 60, no. 1, Jan. 2011, pp. 18+. Accessed 27 June 2022.
  

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