title: Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta.
abstract: Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: DiGirolamo
authors.affiliation: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Singhal
authors.affiliation: Bone & Osteogenesis Imperfecta Department, Kennedy Krieger Institute , Baltimore, MD, USA ; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Bone & Osteogenesis Imperfecta Department, Kennedy Krieger Institute , Baltimore, MD, USA ; Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Germain-Lee