Romosozumab does not improve volumetric bone mineral density at distal radius but is associated with early changes in bone strength: a prospective study

We evaluated how romosozumab affects bone structure, density, and strength at the wrist over 12 months. Volumetric bone mineral density did not increase, but high-resolution quantitative computed tomography imaging showed modest improvements in bone strength. These findings suggest that romosozumab may improve bone quality even in areas where density changes are not seen with standard scans and highlight the importance of using more detailed imaging to fully understand how osteoporosis treatments work across different skeletal sites. PURPOSE: Romosozumab (ROMO) is a monoclonal antibody that inhibits sclerostin, promoting bone formation and suppressing resorption. While ROMO leads to substantial BMD gains at the lumbar spine and the hip, its effects on distal radius volumetric BMD (vBMD) remain unclear. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows for detailed assessment of bone microarchitecture and strength at peripheral regions. We aimed to evaluate the effects of 12 months of ROMO on vBMD, microarchitecture and biomechanical properties of the distal radius using HR-pQCT. METHODS: We did a prospective study on 49 postmenopausal women with osteoporosis treated with ROMO for 12 months who underwent HR-pQCT with Cone Beam CT and microfinite element analysis (uFEA) assessments at baseline, 3, 6, and 12 months. We also performed DXA at lumbar spine, femoral neck, and total hip. HR-pQCT parameters trajectories were analyzed using mixed-effects modeling. RESULTS: No significant increases were observed in cortical or trabecular vBMD or microarchitectural parameters at the distal radius. On the other hand, uFEA showed early increases in cortical failure load and shear strength, suggesting potentially improved bone mechanical behavior. Lumbar spine, femoral neck, and total hip aBMD significantly increased by 11.6%, 8.3%, and 3.1%, respectively (all p < 0.001). CONCLUSION: ROMO treatment was associated with modest early changes in biomechanical parameters, without significant improvement in vBMD at the distal radius. ROMO treatment might improve skeletal health beyond BMD gains.