UCLA

Dental-related trauma such as tooth extraction is one of the major risk factors significantly associated with development of medication-related osteonecrosis of the jaw (ONJ). Tooth extraction is usually performed due to underlying pre-existing pathological inflammatory conditions such as periodontitis but it remains largely unknown whether pathological inflammatory conditions exacerbate ONJ development following tooth extraction, or resolving pathological inflammatory condition before tooth extraction ameliorates ONJ development. The aim of the study is to determine the role of pathological inflammatory conditions in ONJ development induced by tooth extraction in mice. ZOL (Zometa, 125 μg/kg; Novartis Oncology, East Hanover, NJ, USA) or vehicle (veh) solution (0.9% NaCl saline) was i.v. administered bi-weekly throughout the experiment (n = 5-10 per group). One week after ZOL-administration, pathological inflammatory conditions were induced by placing ligature (6-0) on the second maxillary molar for 3 weeks. To resolve ligature-induced inflammation, the ligatures were removed after 3 weeks and allowed to heal for 2 weeks following tooth extraction. After 3 weeks, maxillae were harvested to analyze for the microCT and bone loss as measured from the cement-enamel junction to alveolar bone ridge. Bone necrosis was measured from H&E stained slides by measuring empty lacunae and necrotic bone. Palatal tissues were subjected to qRT-PCR for expression of IL-1B, IL-6, and IL-17. The sectioned slides were stained for tartrate-resistant acid phosphatase (TRAP)+ osteoclasts. Extraction of the tooth with ligature caused increased numbers of empty lacunae and percentages of necrotic bone when compared to that of without ligature. When ligature was removed and allowed to heal before tooth extraction, bone exposure, numbers of empty lacunae, and necrotic bone percentages were all reduced when compared to the unremoved group. These results signify that pathological inflammatory conditions exacerbate ONJ lesions following tooth extraction, and resolution of these conditions before extraction ameliorates ONJ development.