Patient-Oriented Evidence That Matters
Denosumab No Better than Bisphosphonates for Preventing Fracture, and the Cost Is Much Higher
Am Fam Physician. 2020 Sep 15;102(6):375-376.
What is the comparative effectiveness of denosumab (Prolia) and bisphosphonates in adults with osteoporosis?
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−)
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 The authors searched the usual databases but do not report looking for unpublished studies; this is especially important when the research is largely funded by industry.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
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