NON-UNION IN LONG BONE FRACTURES: RISK FACTORS, PATHOPHYSIOLOGICAL MECHANISMS, AND EMERGING TREATMENT STRATEGIES

Abstract

Long bone non-union is a major complication of fracture healing that leads to prolonged disability, repeated surgical interventions, and considerable socioeconomic burden. Its development is influenced by complex interactions among biological, mechanical, vascular, inflammatory, and patient-related factors that disrupt the normal fracture healing process. This review examines the current evidence on the biology of fracture healing, the pathophysiological mechanisms underlying non-union, and the major patient-, fracture-, surgical-, and infection-related risk factors associated with impaired bone regeneration. The clinical role of contemporary imaging modalities, including conventional radiography, computed tomography, magnetic resonance imaging, nuclear medicine techniques, and emerging artificial intelligence-assisted imaging, is discussed with emphasis on their applications in diagnosis, treatment planning, and monitoring of fracture healing. Current management strategies involving mechanical stabilization, biological augmentation, and physical stimulation therapies are  reviewed together with emerging regenerative approaches, including stem cell therapy, tissue engineering, biomaterial-based scaffolds, gene and RNA therapeutics, exosome-based interventions, nanomedicine, and three-dimensional bioprinting. Current challenges related to clinical translation, standardization of treatment protocols, precision medicine, biomarker-guided decision making, and artificial intelligence are also highlighted. Collectively, these advances provide valuable opportunities to improve diagnostic accuracy, optimize individualized treatment strategies, and enhance long-term functional outcomes in patients with long bone non-union..