OLIVERI Maria Beatriz
congresos y reuniones científicas
Romosozumab improves strength at the lumbar spine and Hip in postmenopausal women with low bone mass compared withTeriparatide
KEAVENY TM; CRITTENDEN DB; MICHAEL BOLOGNESE; HENANT HK; ENGELKE K; OLIVERI B; BROWN JP; LANGDAHL BL
Congreso; Reunión Anual American Society for Bone and Mineral Research; 2015
Purpose/Background: Romosozumab is a bone-forming agent that inhibits sclerostin. In a phase 2 study (NCT00896532), 12 months of romosozumab increased DXA bone mineral density (BMD) in postmenopausal women with low bone mass (McClung NEJM 2014). A subset of these women underwent spine and hip quantitative computed tomography (QCT) imaging, confirming the BMD gains (romosozumab vs teriparatide integral volumetric BMD gains of 17.7% vs 12.9% at the spine and 4.1% vs 1.2% at the hip). To investigate the effects of romosozumab on bone strength, we performed a finite element analysis (FEA) on these QCT scans.Methods: This international randomized study enrolled postmenopausal women with lumbar spine, total hip, or femoral neck T scores ≤?2.0 and ≥?3.5. In this analysis, subjects received blinded subcutaneous romosozumab 210 mg monthly, placebo, or open-label teriparatide (20 mcg daily). QCT scans were performed at the L1 & L2 lumbar vertebrae and proximal femur at baseline and month 12. Subject-specific vertebral strength for a simulated compression overload and femoral strength for a simulated sideways fall was estimated blinded-to-treatment using an FDA-approved non-linear 3D FEA (VirtuOst, O.N. Diagnostics). Whole-bone and compartment strength changes were estimated. The ?cortical? compartment was defined as all bone within 2 mm and 3 mm of the periosteal surface for the spine and hip, respectively, plus any high-density bone (>1.0 g/cm3 of apparent density); the trabecular compartment was defined as all other bone. Results: At the spine, romosozumab increased strength from baseline by 27.3% at month 12, which was substantially higher than placebo (?3.9%) and teriparatide (18.5%; Figure A). This strengthening effect was due to contributions from both the ?cortical? and trabecular compartments. At the hip, despite a small sample size for the romosozumab group, strength increased compared with baseline for romosozumab (3.6%), but did not change for placebo or teriparatide (Figure B). Again, both ?cortical? and trabecular compartment changes contributed to the overall strengthening observed with romosozumab. Conclusions: Romosozumab increased strength at the spine and hip over 12 months, with strength improving in the ?cortical? and trabecular compartments at both sites. These strength improvements, documented using a validated method for assessing fracture risk and monitoring treatment, confirm and extend existing data and support romosozumab evaluation in the ongoing phase 3 clinical program.