Abstract
Glucocorticoid-induced osteoporosis (GIOP) is a frequent complication of systemic glucocorticoid (GC) therapy, is the most common form of secondary osteoporosis, and is associated with skeletal fragility and increased fracture risk. A soluble form of BMP receptor type 1A fusion protein (mBMPR1A-mFc) acts as an antagonist to endogenous BMPR1A and could increase bone mass in both ovariectomized and ovary-intact mice, but its effects in GIOP mice remained unclear. The aim of this study was to evaluate the effects of mBMPR1A-mFc on the skeleton in experimental models of GIOP. mBMPR1A-mFc treatment could increase the bone mineral density (BMD), trabecular bone volume, thickness, and number, and cortical thickness, and reduce the structure model index and trabecular separation in GIOP mice. mBMPR1A-mFc treatment could also prevent bone loss and enhance biomechanical strength in GIOP mice by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. Mechanistic studies revealed that mBMPR1A-mFc treatment increased murine osteoblastogenesis by activating the Wnt/β-catenin signaling pathway while decreasing osteoclastogenesis by inhibiting the RANK/RANKL/osteoprotegerin (OPG) signaling pathway. These findings demonstrate that mBMPR1A-mFc treatment in GIOP mice improves bone mass, microarchitecture, and strength by enhancing osteoblastic bone formation and inhibiting osteoclastic bone resorption in GIOP mice and offers a promising novel alternative for the treatment of GIOP.