Preexisting Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced Bisphosphonate-related Osteonecrosis of the Jaw Lesions in Mice

Abstract

Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ.

Effect of Bisphosphonates on the Alveolar Bone of Rats With Glucocorticoids Induced Osteoporosis

“…However, in the present study few empty lacunae were observed in group III treated by Risedronate. This agrees with Song et al 2016 (36), who reported the presence of empty lacunae and necrotic bone in mice treated by bisphosphonates following tooth extraction.…”

“…Bisphosphonates are thought to work by inhibition of osteoclastic activity. Other proposed mechanisms include alteration of bone turnover and inhibition of angiogenesis (36). Several studies have also suggested that bisphosphonates have a stimulatory effect on osteoblast proliferation and differentiation in vitro.…”

Zoledronate treatment duration is linked to bisphosphonate‐related osteonecrosis of the jaw prevalence in rice rats with generalized periodontitis

“…Delaying the start of risk factor medications until surgical sites have healed, and ensuring appropriate perioperative management, including antibiotic coverage, are often effective means to prevent MRONJ associated with dentoalveolar surgery (Dimopoulos et al, ; Hoefert & Eufinger, ; Montefusco et al, ; Ripamonti et al, ; Vandone et al, ). However, periodontitis (PD) and periapical infection (Aghaloo et al, ; Aguirre, Akhter, Kimmel, Pingel, Williams et al, ; Li et al, ; Song et al, ) have also been identified as important risk factors for BRONJ/MRONJ in patients without recent dentoalveolar surgery (Carlson & Schlott, ; Eleutherakis‐Papaiakovou & Bamias, ; Khan et al, ; Marx, ; Voss et al, ). While oral diseases involving the periodontal tissues appear to contribute to MRONJ directly, they may also contribute to cases related to dentoalveolar surgery, since teeth that require extraction often have some degree of acute or chronic infection (e.g., infection from caries, periodontal disease).…”

Medication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: microtomographic, histological and immunohistochemical characterization

“…Namely, the small size of the animal requires reduced amount of the drug, rapid cumulative effects due to rapid mice metabolism, and the possibility of using genetically-manipulated animals to determine a cause-and-effect relationship between the target disruption of a gene and its function [21][22][23]. Several MRONJ models have been developed using mainly C57BL/6 and other mice strains (S1 Table), [15,17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. The C57BL/6 is the most widely used inbred strain and with a large source of genetically modified lines [40].…”