Effects of Local Administration of Novel Bisphosphonate Disodium Dihydrogen-4-[(Methylthio) Phenylthio] Methane- Bisphosphonate (MPMBP) on the Healing of Femoral Bone Defects in Wistar Rats

Abstract

The osteogenic effect of newly developed bisphosphonate (Disodium Dihydrogen-4-[(methylthio) phenylthio] Methane-Bisphosphonate (MPMBP)) was examined for clinical application in bone damage. A bone defect was made in the femur of ninety-seven male Wistar rats. 30µl of MPMBP (experimental group) or saline (control group) was injected around defect once every 3 days. The osteogenic effect to 4 weeks was performed at 1, 2, 3 and 4 weeks (experiment 1). Long-term observation was performed at 12 and 24 weeks after discontinuation of administration of MPMBP at 3 weeks (experiment 2). Newly formed bone was examined radiographically and histologically in both experiments. The elemental analysis was performed to investigate the quality of bone by energy-dispersive X-ray analysis. In experiment 1, newly bone formation is observed in the bone marrow cavity and cortical defect in both groups. The bone volume at 4 weeks was decreased in control group and maintained in experimental groups. In experiment 2, newly formed bone in bone marrow cavity was absorbed at 12 weeks in control group, and showed gradually decrease to 24 weeks in experimental group. The Ca/P of newly formed bone showed little difference between control and experimental groups. It was confirmed that the MPMBP administration had local effects, showing the promotion of new bone formation and long-term bone remodeling.

Potential role of myeloid-derived suppressor cells in transition from reaction to repair phase of bone healing process

“…The immune system plays a crucial role in successful healing of bony injuries 22 . Neutrophils, macrophages, and dendritic cells stimulate osteoclast formation via the helper T cell (Th 17)-mediated RANKL signaling pathway 23 - 25 . On the other hand, Th1 and Th2 T cells inhibit osteoclast formation 26 .…”