GLP-1 receptor agonists demonstrate conflicting effects on bone metabolism, with basic science suggesting enhanced bone mineral density and reduced bone resorption through molecular pathways, while clinical studies yield inconsistent fracture risk outcomes. These medications also complicate perioperative care by affecting gastric motility and creating potential drug interactions during orthopedic procedures. This contradiction highlights a critical gap in our understanding of how these increasingly popular medications affect musculoskeletal health. With millions now using GLP-1 agonists like semaglutide and tirzepatide for diabetes and weight management, the bone health implications become particularly relevant as this population ages and faces higher orthopedic surgery rates. The perioperative challenges add another layer of complexity for surgeons managing diabetic and obese patients who represent growing surgical demographics. While proper glycemic control clearly benefits surgical outcomes, the mixed bone health data suggests we need more definitive long-term studies before fully understanding whether these drugs help or hinder skeletal integrity. This represents an important knowledge gap given the medications' widespread adoption and the aging population's increasing need for joint replacements and spinal procedures.