The biology and treatment of acute long-bones diaphyseal fractures: Overview of the current options for bone healing enhancement.

Diaphyseal fractures represent a complex biological entity that could often end into impaired bone-healing, with delayed union and non-union occurring up to 10% of cases. The role of the modern orthopaedic surgeon is to optimize the fracture healing environment, recognize and eliminate possible interfering factors, and choose the best suited surgical fixation technique. The impaired reparative process after surgical intervention can be modulated with different surgical techniques, such as dynamization or exchange nailing after failed intramedullary nailing. Moreover, the mechanical stability of a nail can be improved through augmentation plating, bone grafting or external fixation techniques with satisfactory results. According to the "diamond concept", local therapies, such as osteoconductive scaffolds, bone growth factors, and osteogenic cells can be successfully applied in "polytherapy" for the enhancement of delayed union and non-union of long bones diaphyseal fractures. Moreover, systemic anti-osteoporosis anabolic drugs, such as teriparatide, have been proposed as off-label treatment for bone healing enhancement both in fresh complex shaft fractures and impaired unions, especially for fragility fractures. The article aims to review the biological and mechanical principles of failed reparative osteogenesis of diaphyseal fractures after surgical treatment. Moreover, the evidence about the modern non-surgical and pharmacological options for bone healing enhancement will discussed.