Efficacy and safety of pharmacologic therapies for prevention of osteoporotic vertebral fractures in postmenopausal women

Abstract

Background: There are many pharmaceutical interventions available to prevent osteoporotic vertebral fractures in postmenopausal women, but the efficacy and safety of these drugs are unknown. This study aimed to investigate the efficacy and safety of drugs in the prevention of osteoporotic vertebral fractures.

Methods: PubMed, Embase, and the Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15, 2020, including postmenopausal women with osteoporosis. Network meta-analysis was conducted based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The relative risk (RR) and 95% confidence interval (CI) were used to report the results. This study was registered with PROSPERO, number CRD42020201167. Main Outcomes were incidences of new vertebral fracture and serious adverse events.

Results: Fifty-five RCTs (n = 104 580) evaluating vertebral fractures of sixteen kinds of pharmacologic therapies were included in the network meta-analysis. Abaloparatide (RR, 0.21; [95% CI, 0.09 to 0.51]), alendronate (RR, 0.55; [95% CI, 0.38 to 0.81]), calcitonin (RR, 0.44; [95% CI, 0.25 to 0.78]), denosumab (RR, 0.33; [95% CI, 0.14 to 0.61]), parathyroid hormone (PTH) (RR, 0.32; [95% CI, 0.10 to 0.97]), risedronate (RR, 0.65; [95% CI, 0.42 to 1.00]), romosozumab (RR, 0.31; [95% CI, 0.16 to 0.61]), strontium ranelate (RR, 0.62; [95% CI, 0.42 to 0.93]), teriparatide (RR, 0.27; [95% CI, 0.17 to 0.43]), and zoledronate (RR, 0.41; [95% CI, 0.93]) were associated with lower vertebral fracture risk compared to placebo. PTH was associated with more adverse event rates. For any two drug treatments, the RR of serious adverse events was not statistically significant. Hormone replacement therapy (HRT) and calcitonin may be slower to work because they have only been shown to reduce the risk of vertebral fractures in long-term (>18 months) follow-up.

Conclusions: A variety of drugs are safe and effective in preventing osteoporotic vertebral fractures. HRT and calcitonin only reduced the risk of vertebral fractures during a follow-up of 21-72 months.

Keywords: Pharmacologic therapy; Postmenopausal osteoporosis; Safety; Vertebral fractures.

Fig. 1

Literature search and screening process.

Fig. 2

Network plots of comparisons for vertebral fractures (A) and serious adverse event (B)-based network meta-analyses. Each circular node represents a type of treatment. The circle size is proportional to the total number of patients. The width of lines is proportional to the number of studies performing head-to-head comparisons in the same study. HRT: Hormone replacement therapy; PTH: parathyroid hormone. The drugs in red font are anti-osteoclast-mediated bone resorption. The drugs in green font are anti-osteoclast-mediated bone resorption and stimulate osteoblasts to form new bone. The drugs in blue font stimulate osteoblasts to form new bone.

Fig. 3

Vertebral fractures and serious adverse events (A) according to the drug-based network meta-analysis in the consistency model. Each cell profile contains the pooled RR and 95% CI; significant results are in bold. Ranking curves of vertebral fractures and serious adverse events (B) indicate the probability of the lowest risk of vertebral fractures and serious adverse events, the second lowest risk, the third lowest risk, and so on.

Fig. 4

Forest plots depicting the direct and indirect results of vertebral fractures of head-to-head comparisons. HRT: Hormone replacement therapy; PTH: parathyroid hormone. ∗Values in brackets are 95% CI.

Fig. 5

Forest plots depicting the direct and indirect results of serious adverse events of head-to-head comparisons. HRT: Hormone replacement therapy; PTH: parathyroid hormone. ∗Values in brackets are 95% CI.

Fig. 6

Clustered ranking plot of drug interventions for vertebral fractures and serious adverse events. HRT: Hormone replacement therapy; PTH: parathyroid hormone.