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Treatment to prevent fractures in men and women with low bone density or osteoporosis: update of a 2007 report

Crandall CJ, Newberry SJ, Diamant A, Lim YW, Gellad WF, Suttorp MJ, Motala A, Ewing B, Roth B, Shanman R, Timmer M, Shekelle PG. Treatment to prevent fractures in men and women with low bone density or osteoporosis: update of a 2007 report. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012.


OBJECTIVES: To update a 2007 systematic review on the effectiveness and safety of treatments to prevent fractures in persons with low bone density or osteoporosis and factors affecting adherence to these treatments, and to assess whether monitoring helps identify those most likely to benefit from treatment and the benefits of long-term treatment. DATA SOURCES: MEDLINE(®), Embase, the Cochrane Database of Systematic Reviews, and Clinical were searched from January 2005 through March 2011. REVIEW METHODS: After review by two investigators against predetermined inclusion/exclusion criteria, we included existing systematic reviews, randomized controlled clinical trials, and large observational studies, where appropriate, for assessment of treatment efficacy, safety, and adherence. RESULTS: Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide reduce the risk of vertebral and nonvertebral fractures among postmenopausal women with osteoporosis. Ibandronate and raloxifene reduce the risk of vertebral but not nonvertebral fractures. Alendronate, risedronate, zoledronic acid, and denosumab prevent hip fractures among postmenopausal women with osteoporosis. Risedronate decreases the risk of vertebral and nonvertebral fracture among men with osteoporosis. Among those treated with glucocorticoids, fracture risk reduction was demonstrated for risedronate and alendronate compared to placebo; and for teriparatide compared to alendronate. Few studies have compared osteoporosis therapies head-to-head. Adherence to pharmacotherapy is poor in patients with osteoporosis, as with other chronic conditions. Many factors affect adherence to medications, including dosing frequency, side effects of medications, knowledge about osteoporosis, and cost. Age, prior history of fracture, and concomitant medication use do not appear to have an independent association with adherence. Dosing frequency appears to affect adherence: Adherence is improved with weekly compared to daily regimens, but evidence is lacking to show that monthly regimens improve adherence over that of weekly regimens. Decreased adherence to bisphosphonates is associated with less than optimal reduction in the risk of fracture. Insufficient evidence is available to make conclusions about how adherence to and persistence with newer osteoporosis therapies compare to that with bisphosphonates. Assessment of adverse effects finds that raloxifene is associated with an increased risk for pulmonary embolism and vasomotor flushing; and limited data support a possible association between bisphosphonate use and atypical subtrochanteric fractures of the femur. Evidence is limited on the utility of monitoring and long-term treatment. CONCLUSIONS: There is a high level of evidence that shows that fracture risk reduction is greatest in women with a diagnosis of osteoporosis and/or prevalent fractures. The level of evidence is low to moderate for fracture risk reduction in postmenopausal women with osteopenia and without prevalent fractures. The evidence is low for benefits of treatment for other populations, including men; for the benefits and risks of long-term treatment; and for the need (if any) for monitoring bone density; and mixed with regard to factors that influence adherence.

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