Intra-oral PTH administration promotes tooth extraction socket healing

Abstract

Intermittent parathyroid hormone (PTH) administration increases systemic and craniofacial bone mass. However, the effect of PTH therapy on healing of tooth extraction sites is unknown. The aims of this study were to determine the effect of PTH therapy on tooth extraction socket healing and to examine whether PTH intra-oral injection promotes healing. The mandibular first molars were extracted in rats, and subcutaneous PTH was administered intermittently for 7, 14, and 28 days. In a second study, maxillary second molars were extracted, and PTH was administered by either subcutaneous or intra-oral injection to determine the efficacy of intra-oral PTH administration. Healing was assessed by micro-computed tomography and histomorphometric analyses. PTH therapy accelerated the entire healing process and promoted both hard- and soft-tissue healing by increasing bone fill and connective tissue maturation. PTH therapy by intra-oral injection was as effective as subcutaneous injection in promoting tooth extraction socket healing. The findings suggest that PTH therapy promotes tooth extraction socket healing and that intra-oral injections can be used to administer PTH.

Keywords: alveolar bone loss; bone remodeling; connective tissue; inflammation; osteogenesis; wounds and injuries.

Figure 1.

PTH therapy increased bone fill and preserved the alveolar ridge. (A) Representative sagittal views of the three-dimensional reconstructions of the mandibles. Arrows indicate the extraction sockets of the mandibular first molars. (B) MicroCT assessment of the tooth extraction sockets. PTH therapy significantly increased bone fill and bone mineral density (BMD) at all time-points compared with the VC group. Trabecular numbers (Tb.N) were significantly higher at day 7 but decreased considerably at day 28 in the PTH compared with the VC group. The numbers of trabeculae in the VC group were relatively constant through day 28. Significantly thicker trabecular bone (Tb.Th) and smaller trabecular separation (Tb.Sp) were noted in the PTH than in the VC group at all time-points. (C) The width (r) of the buccal and lingual bony plates was measured and averaged. The distance (h) between the CEJ line and the bony crest was measured on the buccal side. (D) The average width was significantly thicker in the PTH than in the VC group at days 14 and 28. (E) The vertical bone loss increased in the VC group as healing time increased, while, in the PTH group, vertical bone loss did not change until day 14. PTH therapy suppressed the vertical bone loss significantly at days 14 and 28. n = 8 per group, *p < .05, **p < .01.

Figure 2.

PTH therapy promoted soft-tissue healing. PTH therapy significantly suppressed PMN infiltration (A) and increased the amount of collagen fibers at days 7 and 14 (B). No differences were noted in the thickness of the epithelium (C). PTH therapy did not alter serum calcium levels (D). No statistically significant differences were noted between the PTH and VC groups at any time-point for the TRAcP5b (E) and P1NP (F) levels. n > 6 per group, *p < .05.

Figure 3.

Subcutaneous vs. intra-oral injections, microCT assessment. (A) The effect of PTH therapy for 10 days on hard-tissue healing within the extraction socket was assessed by microCT, and the results were compared between the subcutaneous (sc) and intra-oral injection groups. PTH therapy significantly increased bone fill and BMD regardless of the injection method. Trabecular bone parameters were different between the subcutaneous and intra-oral injection groups. PTH therapy by intra-oral injections increased trabecular numbers (Tb.N) and decreased trabecular separation (Tb.Sp), while PTH therapy by subcutaneous injection increased the thickness of trabecular bone (Tb.Th). (B) The neighboring interradicular bone of the maxillary first molars was assessed for PTH bone anabolic effects by microCT. Regardless of the method of injections, PTH therapy for 10 days induced no detectable bone anabolic effect in interradicular bone parameters. n = 8 per group, **p < .01, ***p < .001.

Figure 4.

Subcutaneous vs. intra-oral injections, histomorphometric assessment. Representative images of the trichrome-stained sections of the extraction sockets of the maxillary second molars in rats receiving the subcutaneous injections (A) and intra-oral injections (B) (Appendix Figs. 1, 2). The results of histomorphometric analysis of the sockets are shown under the images. The yellow dotted lines indicate the outline of the original tooth extraction sockets. Bar = 1 mm. (C) PTH therapy for 10 days significantly increased osteoblast surfaces (OB.S/BS) regardless of the method of PTH administration. (D) Osteoclast surfaces (OC.S/BS) were reduced in the subcutaneous PTH injection animals but increased in those receiving intra-oral PTH injections (Appendix Fig. 3). (E) Both subcutaneous and intra-oral injections of PTH suppressed PMN infiltration, with a significant difference detected only when PTH was administered subcutaneously. (F) Macrophages were visualized with CD68 staining and assessed. No differences were noted between the PTH and VC groups when subcutaneous injections were performed. The intra-oral PTH injection significantly suppressed macrophage numbers compared with the intra-oral VC injection. (G) PTH therapy significantly increased the number of collagen fibers, regardless of the method of administration. (H) No difference was noted in the thickness of the epithelium between the PTH and VC groups, regardless of the administration method. (I, J) Representative photomicrographs of the stained sections of the extraction wounds (upper, HE staining; lower, trichrome staining). Blue-stained fibers in the connective tissue indicate collagen (Appendix Figs. 4, 5). Bar = 250 μm; n > 6 per group, *p < .05, **p < .01, ***p < .001.