This study investigated the effect of romosozumab on bone union in a rat posterolateral lumbar fixation model. Posterolateral lumbar fixation was performed on 8‐week‐old male Sprague Dawley rats (n = 20). For bone grafting, autogenous bone (40 mg) was harvested from the spinous processes of the 10th thoracic vertebra until the 2nd lumbar vertebra and implanted between the intervertebral joints and transverse processes of the 4th and 5th lumbar vertebrae on both sides. Rats were matched by body weight and equally divided into two groups: R group (Evenity®, 25 mg/kg) and control (C) group (saline). Subcutaneous injections were administered twice a week until 8 weeks after surgery. Computed tomography was performed at surgery and week 8 after surgery. The area and percentage of bone trabeculae in the total area of bone fusion were calculated. Statistical analysis was performed using an unpaired t test (p < 0.05). We found that the R group rats had significantly higher mean bone union rate and volume than did the C group rats at all time courses starting week 4 after surgery. The R group had significantly higher increase rates than did the C group at weeks 4 and 6 after surgery. The percentage of bone trabeculae area in the R group was approximately 1.7 times larger than that in the C group. Thus, we demonstrated that romosozumab administration has stimulatory effects on bony outgrowth at bone graft sites. We attribute this to the modeling effect of romosozumab.
Nothing to declare regarding the current report. Approval code: The approval code is No.115 of Eastern chiba medical center. Author contributions: SY wrote the article and MI, SuO, KI, YE, YaS and SeO provided critical comments on the draft of the manuscript. MI, NT, GK, YuS, TA, AW, YA treated the patient. All authors read and approved the final version of the manuscript.
Background Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). Methods We injected MIA into the right knees of eight 6-weeks-old male Sprague–Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. Results Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. Conclusion DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.
In this study, we investigated the effect of romosozumab on bone strength at the fusion site in rats that underwent posterolateral lumbar fusion. For bone grafting, autogenous bone was harvested from the spinous process and grafted between the intervertebral joint and transverse processes of the 4th, 5th, and 6th lumbar vertebra bilaterally along with 40 mg of demineralized bone matrix. Rats were matched by body weight and divided equally into R (romosozumab, 25 mg/kg) and C (control, saline) groups. Subcutaneous injections were administered twice a week until 10 weeks post-operation. Computed tomography was performed 10 weeks post-operation to measure bone fusion rate, fused bone volume, and bone density. The fused area bone strength was also measured using 3-point bending. Results showed that group R rats had significantly higher bone fusion zone volume, bone mineral density, and bone strength than group C rats. Thus, the results demonstrated that romosozumab administration not only promoted osteogenesis at the bone graft site but also affected bone strength. Conclusion We demonstrated that romosozumab administration not only promoted osteogenesis at the bone graft site but also affected bone strength.
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