Bisphosphonates associated with lower fracture risk, not associated with mortality

Lower mortality rates linked to bisphosphonates in previous observational studies might be due to direct biological effects of treatment, authors of a recent meta-analysis noted.

Bisphosphonate treatment may not be associated with reduced overall mortality rates and should only be recommended to reduce fracture risk, a study found.

To assess whether randomized clinical trials demonstrate that treatment with bisphosphonates, particularly zoledronate, is associated with reduced mortality, researchers reviewed 38 randomized, placebo-controlled clinical trials of drug treatments for osteoporosis published after 2009 and published or in press before April 19, 2019. Results were published Aug. 19 by JAMA Internal Medicine.

There were 101,642 unique participants in the meta-analyses of all 38 studies, with 45,594 participants randomized to placebo and 56,048 to treatment. A subset of 21 clinical trials looked at bisphosphonate treatments, with 20,244 participants randomized to placebo and 22,623 to treatment. Six clinical trials looked at zoledronate, with 6,944 participants randomized to placebo and 6,926 to treatment.

No significant association was found between all drug treatments for osteoporosis and overall mortality rate (risk ratio [RR], 0.98; 95% CI, 0.91 to 1.05). Clinical trials of bisphosphonate treatment (RR, 0.95; 95% CI, 0.86 to 1.04) and zoledronate treatment (RR, 0.88; 95% CI, 0.68 to 1.13) showed no association with overall mortality rate; however, for zoledronate, evidence for heterogeneity existed.

The researchers noted that the 25% to 60% reductions in total mortality rates associated with bisphosphonates seen in observational studies were too large to be related to a decrease in fracture risk alone, suggesting that lower mortality rates in these studies might be due to direct biological effects of the treatments. However, this association of decreased mortality with bisphosphonate therapy was not seen in this meta-analysis.

“Drug treatments for patients with osteoporosis should only be recommended for reducing fracture risk in accordance with clinical guidelines,” the authors wrote.