1. Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab use are associated with reduced clinical fractures in postmenopausal patients with osteoporosis.
2. Abaloparatide and teriparatide may increase the risk of withdrawal-associated adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Osteoporosis results in bone weakness and increased susceptibility to fractures. By the standard definition, almost 20% of United States female adults older than age 50 years were estimated to have osteoporosis in 2018, up from 14% a decade earlier, along with more than 4% of males in this age group. However, there is a gap in knowledge as to understanding the treatments to prevent fractures in those with low bone mass or osteoporosis. Overall, this study found that bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab significantly reduced clinical fractures and radiographic vertebral fractures for more than two years. This study was limited by few studies that examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond three years. Nevertheless, these study’s findings are significant, as they demonstrate that several medications significantly reduced clinical fractures in postmenopausal females with osteoporosis. However, some medications may increase withdrawals due to adverse effects.
In-Depth [meta-analysis]: This living systematic review and network meta-analysis included English-language randomized controlled trials (RCTs) in female or male adults with low bone mass or osteoporosis not due to a secondary cause (for example, glucocorticoid therapy) comparing one or more pharmacologic interventions of interest to each other or placebo. Included interventions were bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate), parathyroid hormones (PTHs; abaloparatide and teriparatide), receptor activator of nuclear factor κB ligand inhibitors (denosumab), selective estrogen receptor modulators (SERMs; raloxifene and bazedoxifene), and sclerostin inhibitors (romosozumab). Also included in the review were RCTs reporting fractures as efficacy outcomes (rather than safety outcomes) with 12 months or more of follow-up. The primary outcome measured was study characteristics and outcomes data, including hip, vertebral (clinical or radiological), clinical nonvertebral (symptomatic fractures at sites beyond the vertebrae, which typically excluded minor fractures such as those of the digits), and any clinical fractures (a composite of clinical vertebral and nonvertebral fractures). Outcomes in the primary analysis were assessed via pairwise meta-analyses using a random effects model. Based on the primary analysis, bisphosphonates and denosumab reduced hip, clinical, and radiographic clinical fractures in postmenopausal female adults with osteoporosis. Bisphosphonates for 36 months or more were found to increase the risk for atypical femoral fractures and osteonecrosis of the jaw, but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events. Overall, this study found that several medications, including bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab reduced clinical fractures in postmenopausal female adults with osteoporosis.
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