Optimal Intermittent Administration Interval of Abaloparatide for Bone Morphogenetic Protein-Induced Bone Formation in a Rat Spinal Fusion Model.

Both bone morphogenetic protein 2 (BMP-2) and abaloparatide are used to promote bone formation. However, there is no consensus about their optimal administration. We investigated the optimal administration theory for the pairing of BMP-2 and abaloparatide in a rat spinal fusion model. Group I was only implanted in carriers and saline. Carriers with 3 µg of recombinant human BMP-2 (rhBMP-2) were implanted in other groups. Abaloparatide injections were administered three times a week for group III (for a total amount of 120 µg/kg in a week) and six times a week for group IV (for a total amount of 120 µg/kg in a week) after surgery. They were euthanized 8 weeks after the surgery, and we explanted their spines at that time. We assessed them using manual palpation tests, radiography, high-resolution micro-computed tomography (micro-CT), and histological analysis. We also analyzed serum bone metabolism markers. The fusion rate in Groups III and IV was higher than in Group I, referring to the manual palpation tests. Groups III and IV recorded greater radiographic scores than those in Groups I and II, too. Micro-CT analysis showed that Tbs. Sp in Groups III and IV was significantly lower than in Group I. Tb. N in Group IV was significantly higher than in Group I. Serum marker analysis showed that bone formation markers were higher in Groups III and IV than in Group I. On the other hand, bone resorption markers were lower in Group IV than in Group I. A histological analysis showed enhanced trabecular bone osteogenesis in Group IV. Frequent administration of abaloparatide may be suitable for the thickening of trabecular bone structure and the enhancement of osteogenesis in a rat spinal fusion model using BMP-2 in insufficient doses.

Gait analysis of a patient after femoral nerve and malignant soft tissue tumor resections: a case report.

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.

The effects of romosozumab combined with active vitamin D3 on fracture healing in ovariectomized rats.

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.

Gait analysis of a patient who underwent complete resection of the patella and quadriceps femoris for soft tissue sarcoma.

The knee extension mechanism including the quadriceps femoris muscles and patella plays a crucial role in the stance phase of a normal gait cycle. We performed gait analysis of a patient who had undergone complete resection of the knee extension mechanism. An 8-month-old boy developed infantile fibrosarcoma of the right knee and underwent resection of the quadriceps femoris muscles, patella, and patellar tendon. The gait analysis performed at 8 years of age demonstrated that he could maintain the knee joint extension position during the stance phase. Increased muscle activities in the hamstring and gastrocnemius were observed. The results suggest that the hamstring and gastrocnemius muscles might play a role in maintaining the knee extension position during the stance phase. We suggest the importance of reinforcing these muscles in rehabilitation for patients who lost the knee extension mechanism.

Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model.

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 < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. CONCLUSION: It is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.