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Purpose: We investigated the potential efficacy of abaloparatide (Abalo) and zoledronate (ZA) combination therapy for accelerating femoral union in a rat osteotomy model. Methods: Nine-week-old male Sprague–Dawley rats were randomly divided into four groups ( n = 14 per group): control, abaloparatide (Abalo, 30 μg/kg via subcutaneous injection [s.c.] 5 times per week for 6 weeks), zoledronate (ZA; 0.1 mg/kg via s.c., single dose), and Abalo + ZA. Rats were then subjected to unilateral osteotomy of the femoral shaft, followed by osteosynthesis with intramedullary nailing to establish bone healing models. At 2 and 4 weeks after osteotomy, both femurs were removed from seven rats per group for soft X-ray imaging to evaluate bone union and microcomputed tomography (micro-CT) for bone morphometric evaluation. Blood samples were collected from all rats every 2 week starting 6 weeks pre- to 4 weeks postosteotomy. Toluidine blue staining was used for histopathological evaluation of the undecalcified specimens. Results: Soft X-ray imaging revealed accelerated callus formation, callus maturation, and fracture line closure in Abalo and Abalo + ZA groups compared to ZA and control groups. Micro-CT demonstrated greater cortical bone and trabecular bone to total volume ratios in contralateral (left) femurs of the Abalo + ZA group compared to the Abalo group. Both trabecular and cortical bone mineral densities were also greater in contralateral femurs of the Abalo + ZA group compared to Abalo and ZA groups. Conclusion: These findings suggest substantial additive or synergistic efficacy of abaloparatide plus zoledronate combination therapy for accelerating bone healing following osteotomy and for maintaining normal bone health.

Abstract Background Malignant femoral soft tissue tumors are occasionally resected together with the femoral nerves, but this can cause loss of knee extensor muscle activity. To the best of our knowledge, no previous reports have detailed the gait analysis of such cases in combination with electromyography. Herein, we report the gait analysis of a patient who underwent left groin synovial sarcoma and left femoral nerve resection 12 years ago. Case presentation We analyzed the gait of a 38-year-old man who was able to walk unaided after the resection of a synovial sarcoma in the left groin together with the ipsilateral femoral nerve. The muscle activities of the affected medial (MH) and lateral hamstrings (LH), and lateral heads of the gastrocnemius (GL) were increased during 50–75% of the stance phase. The hip flexion angle of the affected limb was smaller, and the ankle plantar flexion angle of the affected limb was larger than that of the non-affected limb. This means that in the affected limb, the hip and ankle angles were adjusted to prevent knee collapse, and the MH, LH, and GL muscles contributed in the mid- and late-stance phases. Moreover, we found that the hamstring and gastrocnemius of the affected limb worked together to keep the ipsilateral knee extended in the mid-stance phase and slightly flexed in the late-stance phase. Conclusions Patients capable of walking after femoral nerve resection may control their hamstrings and gastrocnemius muscles collaboratively to prevent ipsilateral knee collapse in the mid- and late-stance phases.

Abstract Background In this study, we investigated the potential acceleration of fracture healing and bone mineral density-increasing effects of romosozumab and active vitamin D3 combination therapy for fractures in ovariectomized rats. Methods Ovariectomy was performed on 40 24-week-old female Sprague–Dawley rats. After 8 weeks, the rats were subjected to periosteum removal and osteotomy of the femoral shaft followed by osteosynthesis with intramedullary nailing to create fracture models. The rats were then divided into four groups: C group (control), R group (receiving romosozumab at 25 mg/kg once a month via subcutaneous injection), VD group (receiving active vitamin D3 at 0.2 µg/kg twice a week via subcutaneous injection), and R + VD group. Further, 10 rats were included in a sham group. At 10 weeks after the intervention, both femurs were removed and blood samples were collected from all rats. Soft X-ray imaging was used to evaluate bone union, and microcomputed tomography (micro-CT) was used for bone morphometric evaluation. Toluidine blue staining was used for the histopathological evaluation of the undecalcified specimens, and bone turnover marker levels were measured using enzyme-linked immunosorbent assay. Results Bone morphometry analysis via micro-CT revealed increased mineral density of the trabecular bone in the R + VD group femurs, demonstrating the effectiveness of romosozumab plus active vitamin D3 combination therapy. However, there were no differences in bone union evaluated using soft X-ray imaging, indicating no acceleration of fracture healing. Conclusions Although romosozumab and active vitamin D3 combination therapy increased trabecular bone volume, there was no evidence on its ability to accelerate fracture healing. Graphical abstract

Abstract Background Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated. Methods From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens. Results About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p