Treatment With a Soluble Bone Morphogenetic Protein Type 1A Receptor (BMPR1A) Fusion Protein Increases Bone Mass and Bone Formation in Mice Subjected to Hindlimb Unloading

ABSTRACT Previous work has shown that the soluble murine BMPR1A–fusion protein (mBMPR1A‐mFc) binds to BMP2 and BMP4 with high affinity, preventing downstream signaling. Further, treatment of intact and ovariectomized mice with mBMPR1A‐mFc leads to increased bone mass, and improved bone microarchitecture and strength, via increased bone formation and reduced resorption. In this study, we tested the effects of mBMPR1A‐mFc on disuse‐induced bone loss caused by 21 days of hindlimb unloading (HLU) via tail suspension versus cage controls (CONs). Adult female C57BL/6J mice (12 weeks old) were assigned to one of four groups (n = 10 each): CON‐VEH; CON‐mBMPR1A‐mFc; HLU‐VEH; and HLU‐mBMPR1A‐mFc. Mice were injected subcutaneously with VEH or mBMPR1A‐mFc (4.5 mg/kg, 2×/week). Leg BMD declined in the HLU‐VEH group (–5.3% ± 1.3%), whereas it was unchanged in HLU‐mBMPR1A‐mFc (–0.3% ± 0.9%, p p p JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.