Bisphosphonates in Osteoporosis: Prescribe Only to Reduce Fracture Risk, Not Mortality

The use of bisphosphonates for the management of osteoporosis may not have an influence on overall mortality rate, according to findings from a meta-analysis. The findings suggest that treatment with bisphosphonates for osteoporosis should be recommended only for the prevention of fracture and not for any additional reduction in mortality.

Previous studies have reported that the use of bisphosphonates for the management of osteoporosis is associated with decreased risk of fracture and reduced overall mortality.

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For this study, researchers sought to assess whether randomized clinical trials demonstrated that individuals who received treatment with bisphosphonates, particularly zoledronate, had a reduced overall mortality rate, not just a reduced risk of fracture.

Data from 38 randomized placebo-controlled clinical trials found in the ScienceDirect, MEDLINE, Embase, and the Cochrane Library databases were evaluated. All clinical trials included studied bisphosphonates that have proven antifracture efficacy, that were used at the approved dose for the management of osteoporosis, and that had a duration of use of 1 year or more.

Among the clinical trials, 21 included bisphosphonates and 6 included zoledronate specifically. A total 101,642 unique participants—45,594 of whom were randomly assigned to placebo and 56,048 of whom were randomly assigned to treatment with a bisphosphonate—were included in the final analysis.

No significant association was observed between all agents and overall mortality rate (risk ratio [RR], 0.98; 95% CI, 0.91-1.05).

The clinical trials of bisphosphonates (RR, 0.95; 95% CI, 0.86-1.04) and zoledronate specifically (RR, 0.88; 95% CI, 0.68-1.13) showed no significant association with overall mortality. However, there was evidence for heterogeneity of the results from the zoledronate-specific clinical trials.

“Results of this meta-analysis suggest that bisphosphonate treatment may not be associated with reduced overall mortality rates in addition to decreased fracture risk and should only be recommended to reduce fracture risk,” the authors concluded. “Additional trials are needed to clarify whether treatment with zoledronate reduces mortality rates.”

—Melinda Stevens

Reference:

Cummings SR, Lui L-Y, Eastell R, Allen IE. Association between drug treatments for patients with osteoporosis and overall mortality rates: a meta-analysis [published online August 19, 2019]. JAMA Intern Med. doi:10.1001/jamainternmed.2019.2779.