Effects of pre-extraction intermittent PTH administration on extraction socket healing in bisphosphonate administered ovariectomized rats

Abstract

The purpose of this study was to investigate the effect of administering intermittent parathyroid hormone (iPTH) before tooth extraction versus after tooth extraction on the risk of developing MRONJ in experimental animal model. Twenty-five ovariectomized rats received 6 weeks of bisphosphonate therapy. They were classified into 3 groups, based on the timing of the medication, as Control, Pre-PTH and Post-PTH groups. For Control group, normal saline was administered before and after tooth extraction. iPTH was administered during 4 weeks before tooth extraction for Pre-PTH group and after tooth extraction for Post-PTH group. The animals were euthanized 8 weeks after tooth extraction. Macroscopic, histological, micro-computed tomography (micro-CT), and histomorphometric examinations were conducted. The incidences of impaired healing were 11.11% both in Pre-PTH and Post-PTH groups, which was lower than the Control group (42.86%). Bone healing in the extraction socket, based on micro-CT and histomorphometry evaluations, was best in Post-PTH and worst in Control group. The Pre-PTH group showed moderate healing pattern. Despite of limitations in this study, the authors identified Pre-PTH group seems to have positive effect on extraction socket healing. With regard to timing, administering iPTH after tooth extraction was superior to applying it before tooth extraction.

Figure 1

Effects on the extraction socket healing related to parathyroid hormone (PTH) administration. (a–d) Micro-computed tomography (micro-CT) analysis. In micro-CT analysis, the PTH-administered groups showed higher (a) bone volume/tissue volume (BV/TV), (b) trabecular number (Tb.N), and (c) trabecular thickness (Tb.Th), and (d) lower trabecular separation (Tb.Sp), compared with the Control group. (e) Histomorphometric analysis. The bone area/tissue area (B.Ar/T.Ar) shows a similar pattern as the BV/TV in the micro-CT analysis. *p < 0.05, versus the Control.

Figure 2

Representative images of micro-CT of each group. Insufficient bone healing was observed in control group (yellow arrowhead), whereas good bone healing of extraction socket was observed in pre-PTH and post-PTH groups (white arrow).

Figure 3

Experimental design. Rats (n = 25) underwent ovariectomy, followed by an 8-week waiting period. Zoledronic acid (200 μg/kg) was administered for 6 weeks. Before or after tooth extraction, 80 μg/kg of saline or parathyroid hormone (PTH) was administered daily, depending on the group. The parentheses refer to the period (weeks) taken for the experiments. BP bisphosphonate.

Figure 4

Representative images of (a,b) healing and (c,d) MRONJ, based on hematoxylin and eosin (H&E) staining (magnified × 50). (a,b) The extraction socket is filled with bone completely or partially (asterisk mark). Black arrow indicates fibrotic healing states. (c) The extraction socket shows impaired healing with ulcerative epithelium (arrowhead) and necrotic bone (N). (d) The extraction socket is filled with inflammatory cells, although surrounding bone is intact. The scale bar (black line) indicates 200 μm. Alv. alveolar bone, N necrotic bone, Abs abscess.