The bone healing process is influenced by various physiological factors. Fracture fixation traditionally relied on rigid metallic implants. However, excessively rigid constructs can lead to complications, necessitating revision surgery. This review focuses on approaches to improve bone healing by introducing adequate interfragmentary movement (IFM) at the fracture site. IFM promotes secondary fracture healing and callus formation. Studies suggest that rigid fixation may impair fracture healing by inhibiting callus formation and causing stress shielding. Titanium alloy locking plates have been shown to be biomechanically superior to stainless steel. Flexible fixation and techniques to regulate implant stiffness are crucial for managing fractures with bridge plating. Materials with a lower Young’s modulus balance biomechanical properties. A novel TiNbSn alloy with a low Young’s modulus has been developed to address stress shielding issues. It is effective in promoting osteosynthesis, bone healing, and superior mechanical properties compared with materials with higher Young’s moduli. The enhanced formation of bone and callus associated with TiNbSn alloy suggests its promise for use in fracture treatment plates. Understanding the biomechanics of fracture healing, optimizing fixation stiffness, and exploring innovative materials like TiNbSn alloys, are crucial for advancing approaches to accelerate and enhance bone healing.

Background: Bone grafting is widely used to treat large bone defects. A porous composite of a bioactive octacalcium phosphate material with gelatin sponge (OCP/Gel) has been shown to biodegrade promptly and be replaced with new bone both in animal models of a membranous bone defect and a long bone defect. However, it is unclear whether OCP/Gel can regenerate bone in more severe bone defects, such as a critical-size transcortical defect. Questions/purposes: Using an in vivo rat femur model of a standardized, transcortical, critical-size bone defect, we asked: Compared with a Gel control, does OCP/Gel result in more newly formed bone as determined by (1) micro-CT evaluation, (2) histologic and histomorphometric measures, and (3) osteocalcin staining and tartrate-resistant acid phosphatase staining? Methods: Thirty-four 12-week-old male Sprague-Dawley rats (weight 356 ± 25.6 g) were used. Gel and OCP/Gel composites were prepared in our laboratory. Porous cylinders 3 mm in diameter and 4 mm in height were manufactured from both materials. The OCP/Gel and Gel cylinders were implanted into a 3-mm-diameter transcortical critical-size bone defect model in the left rat femur. The OCP/Gel and Gel were randomly assigned, and the cylinders were implanted. The biological responses of the defect regions were evaluated radiologically and histologically. At 4 and 8 weeks after implantation, CT evaluation, histological examination of decalcified samples, and immunostaining were quantitatively performed to evaluate new bone formation and remaining bone graft substitutes and activity of osteoblasts and osteoclast-like cells (n = 24). Qualitative histological evaluation was performed on undecalcified samples at 3 weeks postimplantation (n = 10). CT and decalcified tissue analysis was not performed blinded, but an analysis of undecalcified specimens was performed under blinded conditions. Results: Radiologic analysis revealed that the OCP/Gel group showed radiopaque regions around the OCP granules and at the edge of the defect margin 4 weeks after implantation, suggesting that new bone formation occurred in two ways. In contrast, the rat femurs in the Gel group had a limited radiopaque zone at the edge of the defect region. The amount of new bone volume analyzed by micro-CT was higher in the OCP/Gel group than in the Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 6.1 ± 1.6 mm³ versus 3.4 ± 0.7 mm³, mean difference 2.7 [95% confidence interval (CI) 0.9 to 4.5]; p = 0.002; intraclass correlation coefficient [ICC] 0.72 [95% CI 0.29 to 0.91]; 8 weeks after implantation: OCP/Gel versus Gel: 3.9 ± 0.7 mm³ versus 1.4 ± 1.1 mm³, mean difference 2.5 [95% CI 0.8 to 4.3]; p = 0.004; ICC 0.81 [95% CI 0.47 to 0.94]). Histologic evaluation also showed there was a higher percentage of new bone formation in the OCP/Gel group at 4 and 8 weeks after implantation (​​4 weeks after implantation: OCP/Gel versus Gel: 31.2% ± 5.3% versus 13.6% ± 4.0%, mean difference 17.6% [95% CI 14.2% to 29.2%]; p < 0.001; ICC 0.83 [95% CI 0.53 to 0.95]; 8 weeks after implantation: OCP/Gel versus Gel: 28.3% ± 6.2% versus 9.5% ± 1.9%, mean difference 18.8% [95% CI 11.3% to 26.3%]; p < 0.001; ICC 0.90 [95% CI 0.69 to 0.97]). Bridging of the defect area started earlier in the OCP/Gel group than in the Gel group at 4 weeks after implantation. Osteocalcin immunostaining showed that the number of mature osteoblasts was higher in the OCP/Gel group than in the Gel group at 4 weeks (OCP/Gel versus Gel: 42.1 ± 6.5/mm² versus 17.4 ± 5.4/mm², mean difference 24.7 [95% CI 16.2 to 33.2]; p < 0.001; ICC 0.99 [95% CI 0.97 to 0.99]). At 4 weeks, the number of osteoclast-like cells was higher in the OCP/Gel composite group than in the Gel group (OCP/Gel versus Gel: 3.2 ± 0.6/mm² versus 0.9 ± 0.4/mm², mean difference 2.3 [95% CI 1.3 to 3.5]; p < 0.001; ICC 0.79 [95% CI 0.35 to 0.94]). Conclusion: OCP/Gel composites induced early bone remodeling and cortical bone repair in less time than did the Gel control in a rat critical-size, transcortical femoral defect, suggesting that OCP/Gel could be used as a bone replacement material to treat severe bone defects. Clinical Relevance: In a transcortical bone defect model of critical size in the rat femur, the OCP/Gel composite demonstrated successful bone regeneration. Several future studies are needed to evaluate the clinical application of this interesting bone graft substitute, including bone formation capacity in refractory fracture and spinal fusion models and the comparison of bone strength after repair with OCP/Gel composite to that of autologous bone.

The global increase in femoral neck fractures due to aging and osteoporosis is a major clinical challenge. The debate on the optimal surgical intervention for femoral neck fractures remains unresolved. This large-scale study explores femoral neck fractures among the elderly, focusing on the comparative outcomes of Total Hip Arthroplasty (THA) versus Bipolar Hemiarthroplasty (BHA) in Japanese patients. Using the Japanese National Administrative Diagnosis Procedure Combination (DPC) database, we studied cases of femoral neck fracture from April 2016 to March 2023, and after propensity score matching by age, sex, and comorbidities, we examined the association between THA, complications, and clinical outcomes, and the usefulness of THA for elderly patients with femoral neck fracture. One-to-one propensity score matching identified 7741 pairs of THA and BHA cases. There was no difference in length of stay between the THA and BHA groups. Significantly more blood transfusions were required in the THA group. There was no significant difference in mortality between the THA and BHA groups, but there was a reduced risk of pneumonia in the THA group, with a ratio of 0.547 (95% CI: 0.418-0.715). On the other hand, the THA group had a higher risk of pulmonary embolism, with a ratio of 1.607 (95% CI: 1.379-1.874). The THA group shows improved discharge rates directly home from the facility where the operation was performed, with a ratio of 1.798 (95% CI: 1.675-1.929). The findings of this research indicate that THA is more effective than BHA in enabling elderly Japanese patients with femoral neck fractures to be discharged directly home and in preventing pneumonia, despite concerns about pulmonary embolism. These findings suggest that THA may improve functional prognosis in elderly patients with femoral neck fractures, although there is a trade-off with an increased risk of pulmonary embolism.

Background: Ti6Al4V alloy, which is commonly used for biomedical applications, has a Young modulus (110 GPa) that is higher than that of human cortical bone (11 to 20 GPa). Using an implant with a material with a low Young modulus that enhances load sharing by the bone even more than those made of Ti6Al4V could be beneficial for bone healing and further reduce the potential for stress shielding. A new β-type TiNbSn alloy has a low Young modulus of approximately 40 to 49 GPa. However, whether the new titanium alloy with a lower Young modulus is advantageous in terms of fracture healing has not been assessed, and a small-animal model seems a reasonable first step in its assessment. Questions/purposes: To assess the impact of a TiNbSn alloy plate with a lower Young modulus compared with a Ti6Al4V alloy plate on fracture healing, we evaluated: (1) bony bridging and callus volume, (2) new bone formation and remaining cartilage tissue, (3) osteoblast activity in the callus, and (4) mechanical strength and stiffness of the callus in bending. Methods: Fracture plates manufactured from TiNbSn and Ti6Al4V alloys, which have Young moduli of 49 GPa and 110 GPa, respectively, were compared. The main reason for using rabbits was the high reliability of the three-point bending mechanical test of the rabbit tibia. Forty-two male Japanese white rabbits weighing 2.8 to 3.4 kg were anesthetized. A 5-cm skin incision was made on the medial side in the mid-diaphysis of the right tibia. Eight-hole plates were used, which were 42 mm long, 5 mm wide, and 1.2 mm thick. Plate fixation was performed using three proximal and three distal screws. After the plate was installed, an osteotomy was performed using a 1-mm-wide wire saw to create a standardized tibial transverse osteotomy model with a 1-mm gap. Bone healing was quantitatively assessed by two nonblinded observers using micro-CT (bony bridging and callus volume), histomorphometry (new bone formation and remaining cartilage tissue), immunohistochemistry (osteoblast activity), and mechanical testing (mechanical strength and stiffness in bending). Measurements on nondemineralized specimens were descriptive statistics due to their small number. Four weeks after osteotomy and fixation, 30 rabbits were euthanized to undergo micro-CT and subsequent mechanical testing (n = 12), histomorphometry and immunohistochemistry with demineralized specimens (n = 12), and histomorphometry with a nondemineralized specimen (n = 6). Eight weeks postoperatively, 12 rabbits were euthanized for micro-CT and subsequent mechanical testing. Results: Intramedullary fracture calluses treated with TiNbSn alloy plates had larger bone volumes and more numerous bridging structures than those treated with Ti6Al4V alloy plates at 4 weeks after osteotomy (Ti6Al4V alloy versus TiNbSn alloy: 30 ± 7 mm³ versus 52 ± 14 mm³, mean difference 22 [95% CI 9 to 37]; p = 0.005; ICC 0.98 [95% CI 0.95 to 0.99]). Histologic assessments demonstrated there was greater new bone formation (total callus: Ti6Al4V versus TiNbSn: 16 ± 4 mm² versus 24 ± 7 mm², mean difference 8 [95% CI 1 to 16]; p = 0.04; ICC 0.98 [95% CI 0.93 to 0.99]; intramedullary callus: Ti6Al4V versus TiNbSn: 6 ± 4 mm² versus 13 ± 5 mm², mean difference 7 [95% CI 1 to 13]; p = 0.02; ICC 0.98 [95% CI 0.95 to 0.99]) and a higher number of osteocalcin-positive cells (Ti6Al4V alloy versus TiNbSn alloy: 1397 ± 197 cells/mm² versus 2044 ± 183 cells/mm², mean difference 647 [95% CI 402 to 892]; p < 0.001; ICC 0.98 [95% CI 0.95 to 0.99]) in the TiNbSn alloy group than in the Ti6Al4V alloy group. At 4 weeks after osteotomy, both bone strength and stiffness of the healed bone in the TiNbSn alloy group were higher than those in the Ti6Al4V alloy group (maximum load: Ti6Al4V alloy versus TiNbSn alloy: 83 ± 30 N versus 127 ± 26 N; mean difference 44 [95% CI 8 to 80]; p = 0.02; stiffness: Ti6Al4V alloy versus TiNbSn alloy: 92 ± 43 N/mm versus 165 ± 63 N/mm; mean difference 73 [95% CI 4 to 143]; p = 0.047). Eight weeks after osteotomy, no between-group differences were observed in the strength and stiffness of the healed bone. Conclusion: The results of this study indicate that TiNbSn alloy plate with a lower Young modulus resulted in improved bone formation and stiffer callus during the early phase (4 weeks after surgery) but not the later phase (8 weeks after surgery) of bone healing. Clinical Relevance: An overly stiff plate may impair callus formation and bone healing. The TiNbSn alloy plate with a low Young modulus improves the early formation of new bone and stiff callus at the osteotomy site compared with the Ti6Al4V alloy plate in the healing process, which may promote bone repair. TiNbSn alloy may be a promising biomaterial for fracture treatment devices. Further research to address concerns about the strength of TiNbSn alloy plates, such as fatigue life and plate fracture, will be necessary for clinical applications, including mechanical tests to verify fatigue life and validation in larger animals with greater body weight.

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Titanium alloys are useful for application in orthopedic implants. However, complications, such as prosthetic infections and aseptic loosening, often occur after orthopedic devices are implanted. Therefore, innovation in surface modification techniques is essential to develop orthopedic materials with optimal properties at the biomaterial–bone interface. In this review, we present recent research on the improvement in the osteoconductivity and antibacterial effect of the Ti-33.6% Nb-4% Sn (TiNbSn) alloy by anodic oxidation and other related studies. TiNbSn alloys are excellent new titanium alloys with a low Young’s modulus, high tensile strength, and with gradient functional properties such as a thermally adjustable Young’s modulus and strength. Titanium dioxide (TiO₂), when obtained by the anodic oxidation of a TiNbSn alloy, improves bone affinity and provides antibacterial performance owing to its photocatalytic activity. The safety of TiO₂ and its strong bonding with metal materials make its method of preparation a promising alternative to conventional methods for improving the surface quality of orthopedic implants. Implementing anodization technology for TiNbSn alloys may alleviate orthopedic surgery-related complications, such as loosening, stress shielding, and infection after arthroplasty.