The Effects of GLP-1 Agonists on Musculoskeletal Health and Orthopedic Care

The global rise in obesity and type 2 diabetes mellitus (T2DM) presents significant challenges in musculoskeletal care, contributing to increased perioperative complications, impaired bone health, and compromised muscle function. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for glycemic control in T2DM, have demonstrated substantial benefits in weight reduction and metabolic regulation. The purpose of this review is to understand the musculoskeletal biologic and clinical implications of GLP-1RAs.

Evidence suggests that GLP-1RAs may impact musculoskeletal health through anti-inflammatory effects, bone metabolism modulation, and alterations in muscle composition. GLP-1RAs may promote osteoblastogenesis while dampening osteoclast activity to maintain bone mineral density. The result on fracture risk is unclear. Additionally, while GLP-1RAs cause lean mass loss, GLP-1RAs appear to preserve skeletal muscle, reduce fatty infiltration, and enhance fiber formation and function. Further, GLP-1Rs are present in synovial tissue and cartilage, demonstrating downregulation of inflammatory molecules and chondrocyte apoptotic pathways, though clinical studies show variable effects in the setting of osteoarthritis. Overall, the heterogeneity in findings underscores the need for further research to delineate the long-term musculoskeletal effects of GLP-1RAs.

Understanding the musculoskeletal impact of GLP-1RAs is critical for optimizing their integration into orthopedic practice. This review explores the orthopedic implications of GLP-1RAs, highlighting their biologic mechanisms and clinical effects on obesity-related joint inflammation and arthropathy, bone mineral density and fracture risk, and skeletal muscle preservation.