An Experimental Study Addressing the Promotion of Mandibular Defect Repair Through the Intermittent Subcutaneous Injection of Parathyroid Hormone

Abstract

Parathyroid hormone (PTH) is a major regulator of bone metabolism. Various animal studies and clinical trials have addressed the treatment of osteoporosis and fracture healing with the intermittent administration of PTH, whereas few studies have investigated the effects of PTH on mandibular defect repair. This study sought to examine the feasibility of using recombinant human PTH (rhPTH) to promote the repair of mandibular defects and to provide a preliminary investigation of the underlying mechanisms of this phenomenon. A mandibular defect model was established using Japanese white rabbits. The experimental animals were randomly divided into a control group that received postoperative subcutaneous injections of normal saline on alternate days and an experimental group that received postoperative subcutaneous injections of rhPTH 25 μg on alternate days. The experimental animals were sacrificed at 1, 2, 3, and 4 weeks after the operation to perform x-ray imaging and bone histomorphometric examinations of the defect areas. Changes in serum levels of bone-specific alkaline phosphatase (bALP) and osteoprotegerin (OPG) over time were examined. Compared with the control group, the experimental group exhibited newly generated bone matrix in the mandibular defect area at earlier stages. In the experimental group, the bone trabeculae were arranged in an orderly manner, and uniform calcification was observed. Marked hyperplasia of osteoblasts was observed in the new bone tissue of the experimental group, but significantly less hyperplasia of osteoblasts was observed in the control group. In the 2 groups, the average serum bALP and OPG levels increased after the operation and then gradually decreased. In the experimental group, levels of bALP and OPG at 1 week and 2 weeks after the operation were significantly different from preoperative levels. In the control group, the OPG level at 2 weeks after the operation was significantly different from the preoperative OPG level. A comparison of serum bALP and OPG levels at each examined time point showed no significant difference between the 2 groups. The intermittent subcutaneous injection of rhPTH 25 μg/day promotes the healing of mandibular defects in rabbits. The application of rhPTH may facilitate mandible regeneration by increasing quantities of osteoblasts, accelerating bone turnover metabolism, and upregulating OPG levels.