Nonbisphosphonates, including denosumab, raloxifene, romosozumab, and teriparatide, significantly reduce vertebral fractures and benefit femoral neck bone mineral density compared with placebo among patients with osteoporosis, according to study results published in Bone.

The researchers searched 9 electronic databases and trial registries from inception through July 2018. Studies that were considered eligible included randomized controlled trials (RCTs) in a population at risk for osteoporotic fracture that compared nonbisphosphonates (denosumab, raloxifene, romosozumab, or teriparatide) with each other; placebo; or bisphosphonates alendronate, risedronate, ibandronate, and zoledronic acid. The researchers used the Cochrane risk for bias tool to assess the quality of studies, and performed network meta-analyses to determine relative treatment effectiveness.

After initially identifying 7898 citations, 46 RCTs of nonbisphosphonates were included, along with an additional 49 RCTS of bisphosphonates for the network meta-analyses.

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For the network meta-analysis assessing vertebral fracture data, 46 RCTs were included. The results indicated that all 4 nonbisphosphonates were significantly more effective compared with placebo. The hazard ratio was 0.23 (95% credible interval [CrI], 0.16-0.32) for teriparatide, 0.25 (95% CrI, 0.15-0.43) for 1 year of romosozumab followed by alendronate, 0.30 (95% CrI, 0.21-0.43) for denosumab, and 0.61 (95% CrI, 0.44-0.80) for raloxifene.

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The network meta-analysis assessing femoral neck bone mineral density included 73 RCTs. The researchers found that all 4 nonbisphosphonate interventions were significantly more effective than placebo. Romosozumab followed by alendronate was linked to the greatest treatment benefit.

The network meta-analysis assessing hip fractures, which included 23 RCTs, found that teriparatide, romosozumab followed by alendronate, and denosumab had a significant benefit compared with placebo.

The researchers noted that their study was limited by its restriction to English-language publications and analysis of only 1 treatment sequence.

“Unlike other [network meta-analyses], this article includes the newer drug [romosozumab] within a [network meta-analysis] against the non-bisphosphonates and bisphosphonates currently recommended for [treatment in the United Kingdom],” the researchers wrote.

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Simpson EL, Martyn-St James M, Hamilton J, et al. Clinical effectiveness of denosumab, raloxifene, romosozumab, and teriparatide for the prevention of osteoporotic fragility fractures: a systematic review and network meta-analysis [published online October 15, 2019]. Bone. doi:10.1016/j.bone.2019.115081