Mechanical Analysis of Romosozumab's Effects on Bone Strength in a Rat Posterolateral Lumbar Fusion Model

This study aimed to evaluate the effects of romosozumab, a humanized monoclonal antibody, on bone healing and mechanical strength in a rat posterolateral lumbar fusion (PLF) model. The primary objective was to determine its potential in promoting bone union and enhancing the structural integrity of graft sites, addressing challenges such as pseudarthrosis and hardware failure in spinal surgeries. These complications are particularly common in osteoporotic patients, where compromised bone quality and reduced healing capacity significantly increase the risk of surgical failure. With an aging global population, osteoporosis-related complications in spinal surgery are expected to rise, necessitating novel interventions to improve outcomes.

Twenty male Sprague-Dawley rats were randomized into two groups: romosozumab-treated (R) and control (C). All animals underwent bilateral PLF surgery involving the placement of autogenous bone grafts harvested from the spinous process combined with a demineralized bone matrix between the transverse processes of the lumbar vertebrae. Subcutaneous injections of romosozumab (105 mg/1.17 mL) or saline were administered twice weekly for 10 weeks. Bone healing was assessed through micro-computed tomography (CT) imaging at baseline and 10 weeks post-surgery. Key metrics included the bone fusion rate, fused bone volume, and bone mineral density (BMD). Additionally, the mechanical strength of the fusion mass was evaluated using a three-point bending test to determine the force required to induce rupture.

The R group exhibited significant improvements across all evaluated parameters compared to the C group. Fused bone volume in the R group was significantly greater at 10 weeks (826.7 ± 27.5 mm³) compared to the C group (652.6 ± 30.7 mm³, p < 0.05), reflecting a higher bone volume growth rate (158.1 ± 12.9% vs. 106.8 ± 10.4%, p < 0.05). BMD at the distal femoral diaphysis was also markedly increased in the R group (830.2 ± 11.1 mgHA/cm³) compared to the C group (725.5 ± 12.1 mgHA/cm³, p < 0.05). Mechanical testing revealed superior compressive strength in the R group, with a rupture force of 312.5 ± 43.2 N versus 209.3 ± 35.4 N in the C group (p < 0.05). These results demonstrate romosozumab's capacity to promote robust bone formation and significantly enhance the mechanical integrity of the fusion mass.

Romosozumab treatment significantly improved bone healing, mineral density, and mechanical strength in a rat PLF model, suggesting its potential as a therapeutic option for enhancing spinal surgery outcomes. By promoting rapid bone formation and increasing bone strength, romosozumab addresses critical challenges such as pseudarthrosis and pedicle screw loosening, which frequently compromise surgical success, especially in osteoporotic patients. These findings underscore the therapeutic promise of romosozumab not only in spinal surgery but also as a broader intervention for bone repair and healing. Further research is needed to explore its dose-response relationship, long-term safety, and efficacy in osteoporotic models. Moreover, the use of biochemical markers and microstructural analyses will help elucidate the underlying mechanisms of its action. With its demonstrated ability to enhance both structural and functional bone properties, romosozumab offers a promising avenue for advancing spinal surgery and improving patient outcomes.