Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: A network meta-analysis.

BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS: We included 107 trials (193,987 postmenopausal women; mean age of 66 years; 55% Caucasian; median follow-up of 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, PTH 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone and calcitonin. Teriparatide, abaloparatide, denosumab and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and SERMs had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.