Which treatment to prevent an imminent fracture?

Purpose: To provide a summarized state of the art of the relative efficacy and rapidity of action of pharmacological treatments to prevent imminent osteoporotic fractures. Methods: We reviewed metanalyses (MA) and network metaanalyses (NMA) published during the last 10 years concerning the pharmacological treatment of osteoporosis. We compared the anti-fracture efficacy and the rapidity of action of various agents versus placebo and versus risedronate. Results: All bisphosphonates decrease the incidence of vertebral fractures compared with placebo. Ibandronate is the only one without demonstrated efficacy against non-vertebral and hip fractures. Zoledronate, denosumab and anabolic therapy are associated with a higher fracture risk reduction than oral bisphosphonates. Compared with risedronate, which significantly reduces the rate of hip fractures, zoledronate, denosumab, teriparatide, abaloparatide and romosozumab are more efficient for vertebral fractures but not for non-vertebral or hip fractures reduction. No studies have compared bone anabolic treatments with zoledronate or denosumab. Oral bisphosphonates significantly reduce fracture risk only after more than one year of therapy. A faster reduction of fracture risk is observed with zoledronate and denosumab, or with anabolic agents. For denosumab and anabolic agents, a sequential treatment is required to keep gains after treatment withdrawal. Conclusions: In patients at high risk of imminent fracture, starting therapy with potent antiresorptive agents or with an anabolic agent seems most appropriate to promptly reduce the fracture risk. Available NMA/MA suggest that, compared to zoledronate and denosumab, anabolic agents have a higher efficacy for vertebral fractures but head-to-head studies are lacking.