Denosumab, a human monoclonal antibody against RANK ligand, is shown to have strong anti-fracture effects in Japanese osteoporosis patients. However, there have been no data showing actions on Japanese bone architecture. Here we show that denosumab continuously improves several geometrical parameters calculated by hip structural analysis for 3 years. Compared to placebo, denosumab significantly increased bone mineral density, cortical thickness and cross sectional area in all of the three analyzed areas: the narrow neck, intertrochanter and femoral shaft. The subsequent derived mechanical parameters, cross-sectional moment of inertia, section modulus and buckling ratio, were also improved by denosumab. In addition, the improvement of these parameters was also observed in the patients that had switched from placebo to denosumab treatment. The present study suggests the structural evidence explaining the strong anti-fracture efficacy of denosumab and its significant effects on cortical bone in Japanese.
Keywords: BMD, bone mineral density; BR, buckling ratio; Bone quality; CSA, cross sectional area; CSMI, cross sectional moment of inertia; CoTh, cortical thickness; DIRECT, Denosumab fracture Intervention Randomized placebo Controlled Trial; DMAb/DMAb, denosumab/denosumab; DXA, dual-energy X-ray absorptiometry; Denosumab; ED, endocortical diameter; FREEDOM, Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months; HSA, hip structural analysis; Hip structural analysis; Japanese; OD, outer diameter; Osteoporosis; PBO/DMAb, placebo/denosumab; RANK ligand; RANK, receptor activator of nuclear factor kappa-B; SM, section modulus.