Enhancement of Bone Augmentation in Osteoporotic Conditions by the Intermittent Parathyroid Hormone: An Animal Study in the Calvarium of Ovariectomized Rat.

Abstract

Intermittent parathyroid hormone (PTH) is the commonly used therapeutic approach for patients with severe osteoporosis. The goal of this study was to elucidate the effect of the intermittent PTH treatment on guided bone augmentation (GBA) in the calvarium of ovariectomized (OVX) rats. Surgical ovariectomy on 14 rats and sham surgery on 7 rats were conducted on all rats as the first surgery. GBA surgery was conducted 8 weeks following the first surgery in the rat calvarium by placing 5-mm-diameter cylindrical plastic caps. Following surgery, rats were treated with 40 μg/kg PTH (OVX-PTH) or saline (Sham-Saline, OVX-Saline) via intraperitoneal injection three times per week during the all-observational period. Longitudinal microcomputed tomography (micro-CT) imaging was performed every 2 weeks following the GBA surgery without euthanasia, and the amount of newly generated bone volume (BV) was calculated. All rats were euthanized 12 weeks after GBA surgery, and histology was obtained. Sections stained with hematoxylin and eosin were used for the quantitative analysis of newly generated tissue, and immunohistology was used to visualize Runx2-positive cells and TRAP-positive cells. Throughout the monitoring period, the BVs of OVX rats without PTH treatment (OVX-Saline) were significantly lower than that of the other two groups at weeks 8 and 12 in micro-CT analysis. During all experimental periods, the BV was highest in the OVX rats that were treated with PTH (OVX-PTH). Histologic analysis confirmed the result of micro-CT, and determined that the OVX-PTH presented a greater number of Runx2-positive cells. The number of TRAP-positive multinucleated osteoclasts was highest in OVX-PTH rats; there were no significant differences between the other two groups. The results of this study suggest that treatment with intermittent PTH was associated with increased newly regenerated bone volume in ovariectomized rat calvarial bone augmentation, which may have important clinical implications.