Abstract
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.
Highlights
Bone homeostasis basically depends on osteoblasts and osteoclasts in a continuous cycle of bone resorption and formation
Studies on the periosteum are essential, given that it plays a crucial role in bone development and the process of fracture healing
Research into the relationship between osteogenesis and angiogenesis is essential because they are intimately linked during bone growth and regeneration in bone modeling and during bone homeostasis in bone remodeling
Summary
In this article the following topics will be analyzed: The role of a specific population (Prx1+ Cells) and its expression marker (Prx1) in fracture repair; integration between the cytoskeleton and the main molecular pathways in relation to the mechanotransmission mechanisms in osteocytes; factors that induce bone formation (type H vessels, endogenousexogenous combined bionic periosteum, after BMP2 stimulation preconditioned cells display increased in-vivo bone formation ability, in vivo sequestration of innate small molecules, phagocytic role of macrophages, morin); inducing bone formation with mesenchymal stem cells (leptin, two protein networks, Trb, Interleukin-1β); factors that delay bone healing (inhibition of estrogen receptor alpha signaling, smoking); studies on diabetes and osteoporosis; an improved method for assessing cell and molecular signals in the reparative callus during fracture healing; a novel experimental model to study fracture healing of the proximal femur; co-culture systems of osteoblasts and osteoclasts (Table 2). The latest advances in intracellular signaling pathways, the osteocyte mechanotransmission system, and bone tissue engineering suggest promising experimental strategies, some of which could be employed in clinical trials [16]
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