Monthly treatment with romosozumab for one year increases bone mineral at the hip, but not the knee, in women with chronic spinal cord injury

Abstract

Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI). To date, most research has focused on pharmaceutical intervention using antiresorptives to prevent bone loss during the acute phase of SCI; however, limited research has investigated treatments for established osteoporosis during chronic SCI. Romosozumab, a monoclonal antibody with both antiresorptive and anabolic effects, has demonstrated significant increases in bone mineral density for women with established post-menopausal osteoporosis. Therefore, the purpose of this study was to examine the efficacy of monthly treatment with romosozumab to improve dual-energy X-ray absorptiometry (DXA) derived areal bone mineral density at the hip, and computed tomography (CT) derived bone mineral content and strength at the hip and knee in women with chronic SCI and an inability to ambulate. Twelve female participants with chronic SCI were recruited to receive one year of monthly subcutaneous injections of romosozumab (210 mg). DXA and CT scans were taken at baseline, and months 3, 6 and 12 to quantify bone mineral, and finite element analysis was used to predict bone strength. Longitudinal mixed effects models were employed to determine the impact of treatment on bone properties. After 12 months of treatment, areal bone mineral density at the lumbar spine and total hip were significantly increased with median changes of 10.2% (IQR: 8.3 – 15.2%, p < 0.001) and 4.2% (IQR: 3.4 – 7.7%, p = 0.009), respectively. Improvements at the hip were primarily due to increases in trabecular, not cortical, bone and effects were sufficient to significantly increase finite element predicted strength by 20.3% (IQR: 9.5 – 37.0%, p = 0.004). Treatment with romosozumab did not lead to any significant improvement in bone mineral at the distal femur or proximal tibia. These findings provide promising results for romosozumab treatment to improve bone mineral and reduce fracture risk at the hip, but not the knee, in women with chronic SCI.