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.

Brittle bone disease: Treating bone and muscle

A protein known to increase bone and muscle mass may herald a new approach to treating brittle bone disease. Many patients with the congenital bone disease osteogenesis imperfecta (OI), also known as brittle bone disease, report fatigue, muscle weakness and intolerance to physical activity. The activin signaling pathway is well known for its ability to regulate bone and skeletal muscle mass. Led by Douglas DiGirolamo from the Johns Hopkins University and Emily Germain-Lee from the Kennedy Krieger Institute/Johns Hopkins University in Baltimore, the researchers treated bone and skeletal muscle in mice with one of the most severe forms of OI (type III) with the soluble activin receptor 2B protein. Four weeks of treatment increased bone and muscle mass to a similar extent to that observed in healthy littermates. The findings offer a promising holistic approach to treating the effects of OI on the musculoskeletal system.

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