Influence of antiresorptive/antiangiogenic therapy on changes in periodontal and oral tissue structures: a histomorphometrical analysis in rats

Abstract

Objective The objective of this study was to investigate the influence of various antiresorptive and antiangiogenic medications on morphological changes in periodontal and oral tissue structures. Materials and methods Fifty-five Wistar rats randomly received dual application (i.e., at baseline and after 12-weeks) of the following medications: (1) amino-bisphosphonate [zoledronate (Zo)], (2) RANKL inhibitor [denosumab (De)], (3) antiangiogenic [bevacizumab (Be)], (4) Zo + Be, (5) De + Be or (6) no medication [Control (Co)]. Periodontal and oral tissue biopsies were obtained at 17 (n = 21 animals, Phase 1, (De = 3, De + Be = 3, Zo = 5, Be = 3, Zo + Be = 2, Co = 5) and 29 (n = 34 animals, (De = 8, De + Be = 6, Zo = 2, Be = 7, Zo + Be = 4, Co = 7, Phase 2) weeks after the second drug application. The following outcomes were histomorphometrically assessed: periodontal space width in the coronal (PLS-C, mm) and apical sections (PLS- A), number of empty alveolar bone lacunae in the coronal, apical sections and at the apex at respective tooth sites (EL – C, EL- A, EL- Ap), mucosal thickness at edentulous alveolar ridge areas (MT, mm), and, when present, associated areas of inflammatory cell infiltrates (ICI, mm2). Results Comparable mean PLS-C, PLS-A, ET-A, ET-C, ET-Ap, and MT values were observed in all experimental groups after Phases 1 and 2. The presence of ICI was identified in 3 animals in the Co group (Phase 1: 1, Phase 2: 2), and 17 animals in the test groups (Phase 1: 4; Phase 2: 14). The estimated ICI surface area was significantly higher in the Zo + Be group, followed by the Zo and Be groups compared to that measured in the Co group. The time (i.e., Phases 1 and 2) was not found to be a predictor for the extent of the ICI area. In all groups, the EL-C, EL-A, and EL-Ap values were significantly higher after Phase 2 compared to those assessed after Phase 1. The MT values were significantly reduced in all groups after Phase 2 compared to those measured after Phase 1. Conclusions The present analysis did not show any marked morphological effects of various antiresorptive and antiangiogenic medications on periodontal and oral tissue structures. The presence of inflammatory cell infiltrates was more frequently observed in the animals administered with antiresorptive and antiangiogenic medications as well as combinations thereof. Clinical relevance: Administration of antiresorptive and antiangiogenic medications may be capable of inducing inflammatory reactions in periodontal tissues.