Emerging Peptide Therapies in Orthopaedics: Evidence, Safety, and Perioperative Implications

Background Peptide therapies have rapidly entered musculoskeletal and orthopaedic care through direct-to-consumer performance clinics and widespread online promotion. Agents such as BPC-157 and thymosin beta-4 derivatives (TB-500) are increasingly used by patients seeking accelerated recovery, despite uncertain efficacy and limited perioperative safety data. Questions/Purposes This scoping review aimed to characterize the available evidence regarding commonly used peptide therapies relevant to musculoskeletal pathology and to examine safety considerations and perioperative implications for orthopaedic surgical patients, with emphasis on total joint arthroplasty (TJA). Methods A scoping review was performed using searches of PubMed/MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov from database inception through the final search date. Studies were selected based on translational relevance to musculoskeletal healing, orthopaedic recovery, and perioperative decision-making. Eligible evidence included preclinical animal studies, mechanistic investigations, and human clinical reports. Given heterogeneity in formulations and outcome reporting, findings were summarized using structured narrative synthesis rather than quantitative pooling. Results The evidence base was dominated by preclinical and mechanistic studies, with limited human clinical outcome data. BPC-157 was the most frequently represented agent, with experimental models suggesting activity involving angiogenesis, inflammatory modulation, and collagen remodeling, but minimal clinical evidence applicable to orthopaedic surgery. Thymosin beta-4 derivatives, GHK-Cu, and endocrine-active agents such as growth hormone secretagogues and IGF-1 analogs demonstrated biologic plausibility but lacked robust orthopaedic outcome data. No high-quality studies directly evaluated perioperative outcomes such as wound complications, hematoma formation, infection risk, or implant-related outcomes in patients undergoing TJA. Unregulated sourcing introduces concerns regarding formulation variability and sterility. Conclusions Peptide therapies are increasingly encountered in orthopaedic practice, yet evidence supporting clinical efficacy and perioperative safety remains limited. In TJA, where wound complications and periprosthetic joint infection carry devastating consequences, uncertainty in product integrity and absence of validated safety data warrant a conservative perioperative approach. Future research should prioritize verified formulations, prospective registries, and clinically meaningful endpoints.