Osteoarticular Surgery Research, Hospital La Paz Institute for Health Research-IdiPAZ, La Paz University Hospital-Autonomous University of Madrid, 28046 Madrid, Spain.
Int J Mol Sci. 2021 Jan 14;22(2):767. doi: 10.3390/ijms22020767.
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.
5%至 10%的骨折无法愈合，这种情况被称为骨折不愈合。在临床实践中，稳定的骨折固定联合自体髂嵴骨移植是治疗的金标准。然而，一些难治性骨折不愈合用这种技术不能得到满意的解决。对于这些病例，根据骨愈合的分子机制，寻求生物替代物，本文综述了最近的研究结果。莫林（一种在古木蓝和美洲商陆树中发现的淡黄色结晶黄酮类色素）的促成骨作用最近被报道，骨形态发生蛋白 9（BMP9）和瘦素的联合使用可能改善骨折愈合。雌激素受体α信号的甲基哌啶基吡唑抑制延迟骨再生。吸烟导致软骨发育障碍、骨骼干细胞和祖细胞的异常活性以及强烈的初始炎症反应。因此，强烈建议在手术前 4 周戒烟。糖尿病动物骨折愈合延迟与 BMP6 缺乏（35 kDa）有关。生物陶瓷和扩展的自体骨髓间充质干细胞的组合是治疗难治性骨折不愈合的一种新的、令人鼓舞的替代方法。
