Anti-osteoporotic Pharmacotherapy and Muscle Outcomes in Osteosarcopenia: a Source-Verified Translational Evidence Map.

Abstract

Anti-osteoporotic drugs are increasingly discussed as candidate dual bone-muscle therapies in osteosarcopenia, yet clinical claims often conflate biological plausibility, observational signals, and randomized efficacy. We conducted a source-verified scoping evidence map and translational review, updated through 25 July 2026 using PubMed/MEDLINE, Europe PMC, and citation tracking. Evidence was classified as primary randomized evidence, secondary randomized analysis, observational human evidence, mechanistic/preclinical rationale, or review-level context; quantitative pooling was avoided because no drug-outcome pair had a sufficiently homogeneous randomized evidence base. Denosumab has the most coherent translational rationale through RANKL/RANK/NF-kB signaling, but randomized long-term-care data were neutral for muscle mass, strength, and performance despite bone mineral density improvement. Long-term-care context may reduce anabolic reserve, but a drug-by-exercise interaction remains unproven. Early pamidronate data in severe pediatric burns support prevention of resorption-linked muscle catabolism rather than reversal of established age-related sarcopenia. Bisphosphonates and teriparatide have preclinical or secondary signals; romosozumab and abaloparatide lack direct clinical muscle-efficacy evidence. Nandrolone is retained only as a historical positive control. Future trials should distinguish prevention from reversal and use factorial or rigorously standardized exercise designs with prespecified strength, muscle-mass, physical-performance, and pathway endpoints.