A Review of Recent Developments in the Molecular Mechanisms of Bone Healing

Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily with this technique. For these cases, biological alternatives are sought based on the molecular mechanisms of bone healing, whose most recent findings are reviewed in this article. The pro-osteogenic efficacy of morin (a pale yellow crystalline flavonoid pigment found in old fustic and osage orange trees) has recently been reported, and the combined use of bone morphogenetic protein-9 (BMP9) and leptin might improve fracture healing. Inhibition with methyl-piperidino-pyrazole of estrogen receptor alpha signaling delays bone regeneration. Smoking causes a chondrogenic disorder, aberrant activity of the skeleton's stem and progenitor cells, and an intense initial inflammatory response. Smoking cessation 4 weeks before surgery is therefore highly recommended. The delay in fracture consolidation in diabetic animals is related to BMP6 deficiency (35 kDa). The combination of bioceramics and expanded autologous human mesenchymal stem cells from bone marrow is a new and encouraging alternative for treating recalcitrant nonunions.

Automated summary

This article reviews recent findings on the molecular mechanisms of bone healing and presents various biological alternatives for treating recalcitrant nonunions, such as using morin, BMP9, and leptin. It also discusses factors that impact bone regeneration, including inhibition of estrogen receptor signaling, smoking-induced inflammatory responses, and delayed fracture healing in diabetic animals due to BMP6 deficiency. The combination of bioceramics and expanded autologous human mesenchymal stem cells from bone marrow is highlighted as a promising alternative for treating nonunions that do not respond well to traditional treatments.