Clinical and Pre-clinical Investigation of Bisphosphonate- Related Osteonecrosis of the Jaw (BRONJ) PDF Download

Author: Zaher Jabbour
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Languages : en
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Book Description
"Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an oral complication found in patients receiving high doses of intravenous bisphosphonates for treatment of cancer or osteoporosis. BRONJ is clinically defined as an area of exposed bone in the maxillofacial region that has persisted for more than 8 weeks in patients undergoing, or with previous bisphosphonate treatment and no history of radiation therapy to the jaws. Many hypotheses have been formulated to explain BRONJ based on a bacterial etiology or the direct effects of bisphosphonates on the jaw bone, soft tissue, or vascularization. Challenges in the management of BRONJ arise since the pathophysiology remains poorly defined. The American Association of Oral and Maxillofacial Surgeons recommend a conservative approach of treatment for BRONJ in its early stages, and surgical intervention for the more advanced disease. An interruption of bisphosphonates therapy also is suggested, depending on the patient's overall condition. To determine the efficacy of different treatment interventions, we conducted a retrospective chart review of patients with BRONJ treated at the Montreal General Hospital. The study revealed that both conservative and surgical treatments were used for patients with BRONJ stage II, but that surgical treatment resulted in a faster resolution of the condition. Based on our chart review, we found that corticosteroids were frequently prescribed to BRONJ patients. Therefore, BRONJ-like disease was induced in rats by administering the bisphosphonate zoledronic acid and the corticosteroid dexamethasone. This pre-clinical model showed that bisphosphonate withdrawal might benefit the outcome by allowing bone remodeling to resume. In addition, this model showed that the combined administration of bisphosphonate and corticosteroid increased the suppression of bone turnover compared to the administration of either drug alone. To further explore the hypothesis that bacterial infection contributes to the development of BRONJ, we used the DNA checkerboard technique to determine whether bacterial probes prepared from human oral bacteria hybridized with the whole genome DNA extracted from the oral cavity of rats. This technique was then used to detect and quantify 43 microbial species relevant to human oral health in samples taken from the oral cavity of patients with BRONJ and rats with BRONJ-like disease. The results suggested that the microbiota of exposed bone in BRONJ patients had a different profile compared to the bacterial profile of other hard and soft tissues of the mouth. This unique microbial profile could have been caused by the medications the patients were taking, including chemotherapy and bisphosphonate. E. corrodens, S. gordonii, and S. constellatus were the three most dominant bacterial species in the exposed bone in addition to other non-pathogenic microbial species, and species linked to periodontal diseases and bone infection. As in the BRONJ patients, the exposed bone in rats treated with bisphosphonate and corticosteroid was colonized mainly by non-pathogenic bacteria. The most abundant species in the site of exposed bone in rats were S. pasteuri, S. parasanguinis, and S. mitis. " --