Among the various post-traumatic fracture treatments, the treatment of osteonecrosis remains one of the challenges faced by orthopedic surgeons worldwide. According to relevant data, delayed fracture healing or bone nonunion occurs in about 5-10% of the approximately 6 million fracture patients occurring in the United States each year [1]. The treatment of bone discontinuity can be divided into surgical treatment, biological and physical therapy, etc. At present, surgical internal fixation of autologous bone grafting is still the main method, while biological therapy and physical therapy are becoming new and effective treatment methods. 1. Bone graft and internal fixation bone graft support the formation of new bone through osteogenesis, osteoconduction and osteoinduction. Commonly used grafts include autologous bone tissue, allogeneic bone tissue, bone replacement materials, and the newly developed growth factors and gene therapy. Currently autologous cancellous bone is still used as the first choice due to its own merits, and allogeneic bone is more widely used. However, it is also extremely difficult for local soft tissue and bone defects when there are more of them. Complex defects of this kind can be repaired with an autologous fibula composite flap graft with blood supply, but the surgery is traumatic, to increase the patient’s pain, technically demanding, and there is a risk of necrosis of the surgically anastomosed vascular embolized tissue flap. Even if the graft is successful, it requires a longer period of shaping to accommodate the physiological function of the tibia. Commonly used bone grafting methods: (1) Free bone grafting: It is a conventional bone grafting method. For small bone defects, cancellous bone with cortex is used for implantation, which can play a filling and supporting role. When fusing tibiofibular bone with bone defect, in addition to bone grafting between tibiofibular bone, bone grafting should be placed at the defect at the same time. (2) Bone graft with vascular tip: it provides good blood circulation for the graft and facilitates healing. Firm internal fixation is directly related to bone healing. Application of compression plate fixation can make close contact with the fracture end, increase longitudinal compression, eliminate stress on the fracture end, facilitate capillary growth and crawling, and promote healing. The compression plate can be used without external fixation, thus allowing early joint and muscle movement, while the application of a normal plate requires a period of cast braking. During surgery, it is always important to remember to preserve as much living tissue as possible, be gentle in your approach, and crush the broken bone fragments of the fracture along with any soft tissue with blood flow should be carefully preserved, as experiments have shown that the blood supply of long bones is closely related to the repair time of their bone tissue [2-3].Marti [4] et al. reported 51 patients with humeral stem osteoconnection treated with a uniform compression plate plus autogenous bone graft, but there was an almost complete plant of the upper arm incision with extensive dissection, serious destruction of blood supply, and high rate of radial nerve injury. Shen Hongxing and Zhang Chuncai et al [5] treated 50 cases of humeral bone discontinuity with the application of Swan Memory Joiner (SMC), and the cure rate reached 98%, which was significantly higher than the current level reported in the literature at home and abroad, and they concluded that the SMC fixed segment was stress-free and shaded, forming a three-dimensional fixed dynamic memory field, and the bone discontinuity appeared “anatomical type” for 3-5 months The “anatomical” plate-like bone replacement occurred in 3-5 months, which “skipped” the shaping period. Patients with bone discontinuity, surgical removal of the scar between the fracture ends, in order to promote fracture healing should be implanted, because the long-term sclerotic bone vitality is very poor, autologous bone graft can reactivate the osteogenic effect, stimulate fracture healing. 2. External fixation In recent years, a large number of cases of bone discontinuity have been treated clinically with external fixation techniques. Bone discontinuity with compression a lengthening provides a new treatment method for infected bone defects. For infected bone defects, the use of compression on the defective end and lengthening of the tibial epiphysis in one phase or in stages (lengthening of the osteotomy site within 15 cm from the infected site) solves the three problems of bone defect, bone discontinuity and limb shortening at one time, and without bone grafting and internal fixation. Bone shortening external fixation solves the problem of large osteonecrosis exposure and large skin defect, not only removes the lesion, but also can use the excess skin flap after shortening to cover the wound, avoiding complicated flap grafting and myocutaneous flap transfer, and can do bone lengthening at the same time or in stages, avoiding bone grafting. Patients underwent limb shortening Ilizarov osteotomy limb lengthening and transmission lengthening after segmental osteotomy, and all patients were cured at an average of 12 months; Yusup Ahmat et al [7] applied Ilizarov technique to treat 61 cases of complex defective bone nonunion of long tubular bone, 29 cases of tibia, 9 cases of femur, 11 cases of humerus, 7 cases of radius, and 5 cases of ulna. The length of the bone defect ranged from 4 to 14 cm, with an average of 6.4 cm. 30 patients with bone defects of 4 to 6 cm were selected to undergo Ilizarov osteotomy limb lengthening, 21 patients with bone defects of 6 to 9 cm underwent Ilizarov osteotomy with post-transfer lengthening, and 10 patients with bone defects of more than 9 cm underwent ipsilateral fibular transfer combined with Ilizarov frame fixation. The average bone lengthening was 4.8 cm; the follow-up time ranged from 10 to 84 months, with an average of 47 months. However, the disadvantage of the Ilizarov technique is that it is technically demanding and complicated to operate, and the surgeon needs to have considerable biological foundation and skilled technique as well as rich experience to ensure the safe and effective use of this method. 3. Physical therapy (1) Low-intensity pulsed ultrasound (LIUS) is a biophysical intervention for fracture healing, which accelerates the healing of fresh fractures and the formation of bone scabs through certain mechanisms. It has been found that LIUS can affect the expression of several genes, including those expressing proteoglycans, which play an important role in endochondral osteogenesis, and the secretion of beta-type transforming growth factor (TGF-b) by osteoblasts, thereby accelerating angiogenesis and increasing local blood flow at the fracture site. Currently there are two forms: percutaneous and transosseous. Mayr E et al [8] conducted a prospective study on the role of pulsed low-intensity ultrasound in fracture healing in 100 selected patients (including 64 patients with delayed healing and 36 patients with bone discontinuity) and concluded that 86% of the patients treated by this method had a positive outcome. Thus, we can see that LIUS is effective as a non-invasive adjunct in the treatment of osteochondral discontinuities, and as a viable post-surgical treatment, it can save patients the pain of reoperation; however, the healing time of osteochondral discontinuities in patients treated with the LIUS method is long (basically more than 5 months); LIUS as a treatment for osteochondral discontinuities was approved by the US Drug and Food Administration in 2000. LIUS was approved by the U.S. Drug and Food Administration in 2000. (2) Electrical stimulation therapy There are two types of methods, invasive and noninvasive, although the conduction pathways and currents are different, all of them can produce low-intensity pulsed currents in the tissue to increase the concentration of calcium ions and certain cytokines (such as IGF-2, TGF-B, PGE2, etc.) in the microenvironment of the fracture end, thus promoting local bone tissue growth and accelerating fracture healing. [9] in a review of the literature compared the effectiveness of electrical stimulation therapy with conventional surgical treatment, with success rates of 81% and 82%, respectively. In the treatment of infected bone nonunion, electrical stimulation was slightly more effective than surgical treatment (cure rates of 81% and 69%, respectively), and for open fractures, surgical treatment was superior to electrical stimulation (cure rates of 89% and 78%, respectively). Indications for electrical stimulation therapy can be: cases of osseous nonunion, failed spinal fusion, congenital pseudarthrosis, etc. The duration of treatment is usually 3-9 months, with some complex cases requiring longer time [10].Luna Gonzalez F et al [11], by applying pulsed electromagnetic wave therapy to 30 patients with routine lower extremity lengthening, found that can electromagnetic waves can promote bone tissue growth and shorten the time of patients with external fixation frames. Electrical stimulation and electromagnetic wave therapy is convenient and economical for the treatment of bone discontinuity, and there is a mature pulsed electromagnetic therapy instrument in the domestic clinic, and there are still problems of indications and timing. (3) Hyperbaric oxygen therapy The application of hyperbaric oxygen can be considered in the treatment of crush injury, osteofascial compartment syndrome, acute post-traumatic ischemia, and chronic osteomyelitis in combination with soft tissue infection, skin defect or after skin flap or bone flap transplantation, etc. Atesalp et al [12] reviewed 14 cases of infected tibial osteochondral nonunion, in which two cases of infection occurred after the completion of surgical treatment and were cured after 20-30 hyperbaric oxygen treatment. Recently, Bennett MH et al [13] reviewed hyperbaric oxygen for the treatment of delayed fracture healing and bone discontinuity, stating that there is insufficient evidence of the effectiveness of hyperbaric oxygen alone in the treatment of delayed fracture healing and bone discontinuity; however, the benefits of hyperbaric oxygen in promoting local vascular growth, limiting infection, and promoting healing can be demonstrated, so the reasonable use of hyperbaric oxygen as an adjunctive Therefore, it is feasible to use hyperbaric oxygen as an auxiliary treatment for bone discontinuity. (4) Extracorporeal shock wave therapy (ESWT) Studies have shown that shock waves cause comminuted fractures at the sclerotic end of bone discontinuity and recanalize the bone marrow cavity. Due to the intact surrounding soft tissue and periosteum, the fragments of bone formed by the shock wave fill in the fracture line. At the same time, local fresh hematoma can be produced. It creates a biological environment similar to a fresh fracture and causes aseptic inflammation. Chooi et al [14] performed extracorporeal shock wave therapy for ESWT in five patients with bone discontinuity, and two of them achieved significant results with a mean time to bone healing of 22 weeks. Although extracorporeal shock wave therapy is a non-invasive treatment with few complications, there is a lack of research results on the exact effect and mechanism of action on tissues and organs, and there are few comparative studies, so it is still only used clinically as an adjunct. 4, osteoinduction therapy osteoinduction (osteoinduction) refers to the process in which undifferentiated mesenchymal cells undergo continuous mitosis and gradually transform into osteoblasts with osteogenic capacity under the action of bone growth factors. The osteoinduction process requires three elements: osteoinductive substances, interrogated mesenchymal cells, and a blood supply environment conducive to bone growth. Growth factors are chemically small peptides that promote the mitotic transformation of undifferentiated interrogative cells into osteoblasts and participate in the formation of bone. Growth factors have osteoinductive effects and are now used in the treatment of non-healing fractures and osteonecrosis. The main factors are TGF-β, BMP and FGF, among others. Experiments have shown that human recombinant BMP-2, BMP-7 complexed with carriers can promote endochondral osteogenesis in the case of segmental bone defects.Mario Rnonga et al [15] conducted an observational, retrospective, non-randomized study of 105 patients with osteonecrosis, dividing all patients into a BMP-7 + autologous bone graft group and a group treated with BMP-7 alone, with a mean follow-up of 29.2 months, the results showed a mean healing time of 7.9 months and a success rate of 88.8%, with no statistical difference between the two groups. colnot C et al [16] concluded from animal experiments that metalloproteinase 9 (MMP9) plays a role in promoting cartilage formation and osteoblast differentiation in fracture repair, but further clinical trials are needed. Bone induction requires the expression and mediation of growth factors, and as the study of osteoinductive growth factors progresses, new ways to promote fracture fracture healing are gradually being found. 5, percutaneous autologous red bone marrow transplantation autologous red bone marrow has osteogenic effects, and one week after percutaneous injection of autologous bone marrow at the site of bone defect was seen in animal experiments, the bone marrow component was formed at the center of the bone defect area. A large amount of new cartilage tissue with active proliferation was seen in the tissue section. By 2-3 weeks after the injection, bone trabeculae appeared in the cartilage tissue and gradually joined together to form a sheet, and regular X-ray observation showed that new bone formation gradually increased in the bone defect area and the gap between the bone defects became smaller, which confirmed the obvious osteogenic effect of autologous bone marrow transplantation in the bone defect area. Autologous bone marrow has the advantages of wide source, easy to take, simple operation, less complications in the donor area, and not restricted by soft tissue conditions, etc. This method is a feasible treatment. 6. Gene therapy Gene therapy is a newly developed technology. Through a special vector to transfer the target gene to a specific location to be expressed, producing a therapeutic protein. Gene therapy is divided into local treatment and systemic treatment. For local treatment of non-healing fractures, percutaneous translocation of the gene to the non-healing fracture end by adenovirus is feasible, and the translocated gene is expressed locally for at least one month [17]. The gene transfer system is the key to gene therapy for any disease and is the main factor limiting the development of gene therapy. Without a suitable system, gene therapy is unlikely to be extended for clinical treatment of fracture healing and may also require tissue engineering techniques to provide scaffolds for genetically engineered cell growth for large bone defects caused by osteonecrosis. In conclusion, gene therapy is still in the exploratory stage, and it is believed that with the development of technology and in-depth research, satisfactory results will eventually be achieved. In conclusion, for the treatment of bone discontinuity, endosteal autologous bone grafting is currently the main treatment. With the deepening of basic and clinical research on fracture and the development of bioengineering technology, great progress has been made in the treatment of bone discontinuity, but we should choose appropriate treatment methods according to different situations and different fracture sites in order to achieve better results.