One of the complications of both surgical and non-surgical treatment of fractures is the development of non-union. The 5–10% incidence of non-union quoted in the international literature is thought to be an underestimate of the real magnitude of this clinical problem. The etiology of atrophic non-union is multifactorial, involving biological, mechanical, infectious, and host-related factors. Much of the evidence regarding its pathogenesis is heterogenous and largely hypothesis generating. This heterogenicity has contributed to the wide range of treatment strategies used to address an atrophic non-union, with variable success rates. This structured narrative review summarizes current insights into the pathogenesis of atrophic non-union, including the inflammatory and immune response, the role of mesenchymal stem cells, bone morphogenetic protein, and the mechanisms of remodeling and angiogenesis. It also outlines an algorithmic approach to management, including the exclusion of occult infection, assessment of mechanical stability, optimization of modifiable host factors, and, finally, a graded approach to enhance the biological and mechanical environment of the non-union.
Giannoudis et al. (2026) studied this question.