Denosumab was superior to bisphosphonates for increasing bone mineral density (BMD), and possibly for reducing fracture risk, in patients with osteoporosis or low BMD, according to a report published in the Journal of Clinical Endocrinology & Metabolism.
Although bisphosphonates and denosumab are both commonly used for osteoporosis therapy, it remains unclear which antiresorptive agent is more effective in terms of BMD increase and fracture risk. To optimize osteoporosis treatment initiation and monitoring, investigators sought to establish the relative efficacy of denosumab vs bisphosphonates.
A meta-analysis examined 10 head-to-head comparisons of bisphosphonates and denosumab from randomized controlled trials, published between 2006 and 2018, involving a total of 5361 participants (mean age range, 63 to 78 years; 99.0% women) with low BMD or osteoporosis. Eight studies lasted 12 months, and 2 studies lasted 24 months. Inclusion criteria required denosumab 60 mg to be administered subcutaneously every 6 months for at least 12 months; bisphosphonates included alendronate (35/70 mg weekly), zoledronic acid (5 mg yearly infusion), and ibandronate and risedronate (both 150 mg monthly). Alendronate was most frequently prescribed, and was used as comparator in 6 trials.
The primary outcome was mean BMD percentage change over the course of 12 months at 3 sites, as measured by dual-energy X-ray absorptiometry. Secondary outcomes included the same measure at 24 months, fracture incidence at 12 and 24 months, and adverse events at 12 months. Random effects modeling was employed and risk ratios (RRs) were calculated.
At 12 months, denosumab increased mean BMD significantly more than bisphosphonates at the lumbar spine (mean difference, 1.42%; 95% CI, 0.95%-1.89%; P <.001), total hip (mean difference, 1.11%; 95% CI, 0.91%-1.30%; P <.001), and femoral neck (mean difference, 1.00%; 95% CI, 0.78%-1.22%; P <.001). After 24 months, denosumab still significantly outperformed bisphosphonates in raising BMD, with mean differences of 1.74% (95% CI, 1.05%-2.43%; P <.001), 1.22% (95% CI, 0.66%-1.77%; P <.001) and 1.19% (95% CI, 0.65%-1.72%; P <.001) at the lumbar spine, total hip, and femoral neck, respectively.
When comparing denosumab with bisphosphonates, at 12 months, there was no significant difference between the 2 treatment groups in terms of any fracture (RR, 1.32, 95% CI 0.93-1.87) or osteoporotic fracture (RR, 0.92; 95% CI, 0.39-2.15) incidence. However, at 24 months, there was 1 study that showed a significantly reduced osteoporotic fracture risk for denosumab vs alendronate (RR, 0.51; 95% CI, 0.27-0.97); there was still no difference in risk for any fracture (RR, 0.81; 95% CI, 0.47-1.41). When comparing the safety profiles of denosumab and bisphosphonates, there were no significant differences in total adverse events (RR, 0.99; 95% CI, 0.95-1.03) or severe adverse events (RR, 1.02; 95% CI, 0.79-1.31). Subgroup analysis revealed that patients who received previous bisphosphonate treatment still showed greater lumbar spine BMD improvement with denosumab compared with bisphosphonates.
Study strengths included incorporation of BMD and fracture incidence at 24 months and subgroup analysis of prior bisphosphonate use. Study limitations included lack of treatment allocation concealment in some trials, only moderate quality fracture evidence, and significant outcome heterogeneity.
“Denosumab improved BMD significantly more than bisphosphonates at the lumbar spine, total hip and femoral neck at 12 and 24 months,” summarized the authors, who recommended that future research confirm this relative efficacy via larger sample sizes and longer trials.
Please see original article for funding information and conflicts of interest.
Lyu H, Jundi B, Xu C, et al. Comparison of denosumab vs. bisphosphonates in osteoporosis patients: A meta-analysis of randomized controlled trials [published online December 10, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-02236