Bone Abstracts

Treatment with sclerostin antibody (Scl-Ab) increases bone formation and strength in animal models. Here, we aimed to i) characterize the longer-term effects of Scl-Ab on bone in cynomolgus monkeys (cynos) and ovariectomized (OVX) rats and ii) test whether follow-up treatment with OPG-Fc would maintain the bone mass gains induced by Scl-Ab in OVX rats. In the cynos study, 3 to 5-year-old male cynos were treated for 6 months with weekly SC injections of vehicle (Veh), 3, 10, or 100 mg/kg Scl-Ab. Serum osteocalcin peaked within the first 3 months of Scl-Ab treatment and returned toward baseline levels at month 6.Scl-Ab dose-dependently increased BMD, cortical thickness, trabecular bone volume, and yield load of lumbar vertebral bodies. Positive correlations between BMD and yield load were observed across all groups. In the OVX rat study, 6-month-old OVX rats (2 months post-OVX) were treated with Veh or Scl-Ab (25 mg/kg, SC, 1x/week) for 6, 12, or 26 weeks. Another group of OVX rats was treated with Scl-Ab for 6 weeks and then was transitioned to Veh or OPG-Fc (10 mg/kg, SC, 2x/week) for an additional 6 or 20 weeks. BMD increased progressively up to week 26 with continuous treatment. Trabecular, endocortical, and periosteal bone formation rates (BFR/BS) increased and peaked at week 6.Trabecular and endocortical BFR/BS in the Scl-Ab group gradually declined but remained significantly greater than OVX controls at weeks 12 and 26, while periosteal BFR/BS returned to the level of OVX controls at week 26.Transitioning to OPG-Fc maintained the bone mass and bone strength gains induced by Scl-Ab upon discontinuation of Scl-Ab. These data illustrate that longer-term treatment with Scl-Ab progressively increased bone mass and bone strength in both monkey and rodent models. These results also support the strategy of using anti-resorptive agents to maintain Scl-Ab-induced bone gains.