Risk Factors and Prevention Strategies for Complex Regional Pain Syndrome Following Fractures: A Scoping Review

Complex regional pain syndrome (CRPS) is a neuropathic pain disorder characterized by pain disproportionate to the severity of the inciting injury, persisting beyond the expected period of tissue healing. CRPS can significantly impact functional outcomes, but despite increasing research, risk factors and preventive strategies remain incompletely characterized. The objective is to map the existing evidence on risk factors and preventive strategies for CRPS following fracture, including trauma-related, surgical, and patient-related contributors, and identify gaps in current prevention and risk stratification approaches. A comprehensive search of PubMed, Embase, and Scopus was conducted from database inception through March 17, 2026. Eligible studies included human studies of any design evaluating CRPS risk factors or prevention following fracture. Two independent reviewers performed screening and data extraction. Data was synthesized narratively. Thirty-one studies were included. Preventive strategies most involved early mobilization and vitamin C supplementation, though evidence for vitamin C was heterogeneous. Limited evidence suggested potential benefit from aspirin and N-acetylcysteine. Female sex, psychiatric comorbidities, high pain intensity, and fracture severity were the most consistently reported risk factors. Evidence was largely derived from observational studies. Evidence supporting prevention strategies for CRPS remains limited and heterogeneous. Early mobilization appears beneficial, while pharmacologic strategies require further evaluation and validation. Identified risk factors highlight the multifactorial nature of CRPS and underscore the need for validated risk stratification tools and high-quality prospective studies.