Clinical Question

What is the comparative effectiveness of denosumab (Prolia) and bisphosphonates in adults with osteoporosis?

Bottom Line

This meta-analysis found no evidence that the monoclonal antibody denosumab reduces the risk of fracture more than bisphosphonates. A one-year supply of denosumab costs $2,453 in the United States (http://www.goodrx.com; accessed January 29, 2020) and $758 in Canada (https://www.formulary.health.gov.on.ca/formulary/; accessed January 29, 2020). (Level of Evidence = 1a−)

Synopsis

This meta-analysis of randomized trials compared the monoclonal antibody denosumab with a bisphosphonate. The authors searched the usual databases but do not report looking for unpublished studies; this is especially important when the research is largely funded by industry. They identified 10 studies that compared denosumab with one of four bisphosphonates, most often alendronate (Fosamax) (n = 6). There were a total of 5,361 patients, with a mean age ranging from 63 to 78 years; 99% were women. Only 13% had a previous fracture, and 29% had experienced no previous treatment for osteoporosis. It is not clear whether treatment-naive patients would have had different results than those already taking a bisphosphonate. All patients were also concomitantly taking calcium and vitamin D supplements. The authors did a limited assessment of risk of bias (not judging the overall risk of bias of each study), but found a number of flaws: open-label design in five studies, masked outcome assessment in only three studies, failure to conceal allocation in three studies, and no description of how randomization was performed in two studies. These biases would tend to favor the novel therapy. The authors found that denosumab leads to a greater increase in bone density. Regarding primary patient-oriented outcomes, there was no significant difference in the risk of any fracture based on five studies with 3,540 patients. The trend was toward more fractures with denosumab (relative risk = 1.32; 95% CI, 0.93 to 1.87; pooled absolute risks were 4.0% vs. 3.1%). There was also no difference in the risk of osteoporotic fracture at 12 months based on reporting from three studies with 1,999 patients (relative risk = 0.92; 95% CI, 0.39 to 2.15). There was no difference between groups in adverse events or severe adverse events. The authors estimate that up to three unpublished negative trials may be out there.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Government

Setting: Various (meta-analysis)

Reference: Lyu H, Jundi B, Xu C, et al. Comparison of denosumab and bisphosphonates in patients with osteoporosis: a meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2019;104(5):1753–1765.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.