Four weeks of romosozumab treatment increases trabecular bone volume and differentially improves cortical bone in young and aging mice with chronic kidney disease.

Chronic kidney disease (CKD) leads to significant bone loss and high risk of fractures. Fractures are even more prevalent in the aging population with CKD. Cortical bone is particularly impacted in CKD due to cortical thinning and the development of cortical porosity. The goal of this study was to assess the impact of romosozumab, a bone anabolic therapy, on cortical bone in young and aging mice with adenine-induced CKD. Male C57Bl6/J mice, aged 16- and 66-weeks, were given 0.2% dietary adenine to induce CKD. Eight weeks after induction of CKD, a subset of young and aging adenine-CKD mice were given romosozumab (10 mg/kg, 1x/week for 4 weeks); the study also included age-matched healthy controls. At the study endpoint, all adenine-CKD mice had high blood urea nitrogen and parathyroid hormone compared to controls. Romosozumab-treated groups of both ages had higher trabecular bone volume due to increased trabecular thickness, indicating an anabolic effect of therapy. Romosozumab-treated young mice had higher midshaft femur cortical bone area and cortical thickness, but there were no differences in cortical porosity compared to untreated adenine. Aging mice had no differences in cortical thickness, but cortical pore number was lower with romosozumab treatment. Four-point-bending mechanical tests showed 20% higher ultimate force with romosozumab treatment in both ages, statistically different from untreated adenine in the young cohort. These data demonstrate positive cortical bone effects from four weeks of romosozumab treatment in both young and aging mice with established CKD.