Mandibular bone and gingival epithelium during bisphosphonates treatment: an experimental study

Abstract

Bisphosphonates (BP) are stable analogues of pyrophosphate with a P-C-P structure and 2 side chains attached to the carbon atom. Intravenous bisphosphonates are primarily used and effective in the management of cancer-related conditions in the context of solid tumors, such as breast cancer, prostate cancer, and lung cancer. Moreover bisphosphonates are subministred to patients with metabolic bone disease such as osteoporosis and Paget disease. Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is a really complication of intravenous bisphosphonates therapy in patients with cancer. It is common knowledge that the jaws have a greater blood supply than other bones and a fasterbone turnover rate, related both to their daily activity and presence of teeth which mandates daily bone remodeling around the periodontal ligament; moreover bisphosphonates toxicity to epithelial cells has been well documented. On this basis, the aim of this experimental study is to evaluate the pathological changes of the mandibular bone and oral mucosa in rat treated with bisphosphonates. In details we have analyzed, by immunoistochemical and scanning electron microscopic methods, biopsy of mandibular bone and of gingival mucosa in rat treated with bisphosphonates after 7, 15, 30, 45, 60 days of assumption of drugs and after 7 and 30 days from the end of the treatment. Our results show great area demineralization bone mixed to normal bone, moreover in the demineralization bone it’s possible to observe numerous micro lacunae. In the correspondence samples of gingival epithelium we observe changes of histological structure and the disappearance of protein adhesion system cells to cells and cells to matrix. On this basis it is intriguing to speculate that the adverse effects of BP on oral epithelium may play a critical role in the initiation of BONJ an “outside-in” hypothesis.