Myostatin inhibition from preconception through lactation improves maternal muscle and skeletal health in the osteogenesis imperfecta murine mouse model.

Osteogenesis imperfecta (OI) is a rare type I collagenopathy characterized primarily by skeletal fragility. Despite extensive genetic and clinical understanding of OI, there is no cure and current treatment strategies are not compatible with pregnancy or lactation. Pregnancy and lactation are natural periods of maternal bone loss, as calcium is extracted from maternal bone to support offspring skeletal development, further challenging maternal musculoskeletal health in OI. We hypothesize targeting muscle-bone crosstalk through pharmacological myostatin inhibition in utero can improve maternal musculoskeletal health and reduce maternal bone loss during pregnancy and lactation. Previous attempts to increase muscle and bone mass in the osteogenesis imperfecta model mouse (oim) demonstrated prenatal administration of anti-myostatin antibody (Mstn-Ab) was safe for gestation and fetal development. The current study examines the impact of Mstn-Ab treatment on maternal musculoskeletal health in wildtype (WT) and +/oim dams during preconception, pregnancy, and lactation. Mstn-Ab treatment improved maternal WT and +/oim muscle mass and cortical bone outcomes compared to control antibody (Ctrl-Ab) treatment following lactation. As maternal OI is a risk factor for uterine rupture, a secondary aim was to evaluate the uterine biomechanics of WT and +/oim dams following Mstn-Ab treatment. Uterine biomechanical integrity was reduced in both virgin oim/oim and postpartum +/oim mice relative to WT littermates but was unchanged by maternal myostatin status. These findings suggest myostatin inhibition from preconception through postpartum provides a promising therapeutic strategy to increase maternal musculoskeletal health in OI.