The Efficacy and Safety of Abaloparatide in Osteoporosis: A Systematic Review and Meta-Analysis.

Background/Objectives: Abaloparatide is an osteoanabolic therapy used in patients at high risk of fracture; however, the breadth of evidence across routes, comparators, and sequential strategies has not yet been comprehensively summarized. This study aimed to evaluate the efficacy and safety of abaloparatide for reducing fractures and improving bone mineral density (BMD) in adults with osteoporosis. Methods: Following PRISMA 2020, we searched PubMed, Embase, CENTRAL, and Web of Science (2016-2024) for randomized controlled trials and comparative real-world studies. Additional meta-analyses and network meta-analyses were included as contextual evidence but not pooled to avoid double-counting. Primary outcomes were vertebral, non-vertebral, and hip fractures; secondary outcomes included percentage change in BMD and safety endpoints. Random-effects models were used; heterogeneity, influence analyses, and prediction intervals were examined. Risk of bias was assessed using RoB 2 and AMSTAR 2. Results: Nine quantitative evidence sources met the criteria. Abaloparatide reduced vertebral fractures (RR 0.13-0.21) and showed moderate reductions in non-vertebral fractures. Lumbar spine BMD increased substantially, while hip and femoral neck gains were smaller and heterogeneous. Hypercalcemia risk was consistently lower compared to teriparatide. Transdermal delivery was less effective, and sequential abaloparatide → antiresorptive therapy further reduced fractures. Serious adverse events were not increased. Conclusions: Abaloparatide provides strong vertebral protection, significant BMD improvement, and shows a favorable calcemic profile, with moderate certainty for non-vertebral effects. Evidence in men and long-term safety remains limited.