Fracture nonunion etiology, diagnosis, and treatment: current understandings and approaches

Abstract

Fracture healing is a carefully orchestrated process that closely resembles embryonic skeletal development. In 5-10% of all fractures however this process arrests or is impeded, creating a nonunion of bone across the fracture site that severely complicates patient recovery at great economic cost. The pathophysiology of this complication remains largely unknown, although the disruption of specific cytokine signaling pathways, lack of osteogenic cells, vascular disruption, and a suboptimal mechanical environment may all contribute. Smoking, diabetes, and the use of NSAIDs have also demonstrated associations with nonunion. Diagnosis of a nonunion has also proven difficult as radiographic and clinical assessments remain the gold standard but are largely subjective. Following a diagnosis, surgical intervention is typically pursued and augmented with pharmacologic agents and bone stimulators, although evidence for the effectiveness of both remains limited.

The future of nonunion understanding and diagnosis are coupled, as current research into the complication’s pathophysiology hopes to elucidate biologic markers of bone healing potentially disrupted in nonunion and detectable in the serum. The use of these markers in addition to the expanded use of validated radiographic scoring present the most promising future diagnostic tools. Advanced grafting techniques and compounds as well as stronger evidence-based pharmacologic augmentation seek to improve outcomes after treatment as well. Overall, this review seeks to provide a comprehensive report of current understandings, diagnostics, and treatments for fracture nonunion and the evidence that supports them, as well as present current and planned future research aimed at developing more efficacious diagnostic and therapeutic modalities.