Treatment with soluble bone morphogenetic protein type 1A receptor fusion protein alleviates irradiation-induced bone loss in mice through increased bone formation and reduced bone resorption.

An increased fracture risk is often observed in cancer patients undergoing radiotherapy (RT), particularly at sites within the field of radiation. Therefore, the development of appropriate therapeutic options to prevent RT-induced bone loss is urgently needed. A soluble form of the BMP receptor type 1A fusion protein (mBMPR1A-mFc) serves as an antagonist to endogenous BMPR1A. Previous studies have shown that mBMPR1A-mFc treatment increases bone mass in both ovary-intact and ovariectomized via promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The present study was designed to investigate whether mBMPR1A-mFc administration prevents radiation-induced bone deterioration in mice. We constructed an animal model of radiation-induced osteoporosis by exposure to a 2-Gy dose of X-rays. Micro-CT, histomorphometric, bone-turnover, and mechanical analyses showed that mBMPR1A-mFc administration prevented trabecular microarchitecture deterioration after RT because of a marked increase in bone formation and a decrease in bone resorption. Mechanistic studies indicated that mBMPR1A-mFc administration promoted osteoblastogenesis by activating Wnt/Lrp5/ß-catenin signaling while decreasing osteoclastogenesis by inhibiting the RANKL/RANK/OPG pathway. Our novel findings provide solid evidence for the application of mBMPR1A-mFc as a therapeutic treatment for radiation-induced osteoporosis.

A soluble bone morphogenetic protein type 1A receptor fusion protein treatment prevents glucocorticoid-Induced bone loss in mice.

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/ß-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.