Osteonecrosis of the jaw (ONJ) is a recently described major complication of long-term bisphosphonate (BP) treatment. BPs are potent inhibitors of bone resorption used in the treatment of multiple myeloma, skeletal metastases of solid tumors, hypercalcemia of malignancy and osteoporosis. Most patients present with painful exposed avascular bone in either or both jaws that simulates """"""""tooth-ache"""""""" or bone infection. Currently, there is no effective treatment for ONJ. Periodontal disease is a commonly reported risk factor for ONJ. However, most of the information about these risk factors has been obtained through case reports, and there is an immediate need for matched case-control and prospective studies to confirm this association. The overall goal of current exploratory proposal is to perform a matched case-control study to test the hypothesis that periodontal disease and periodontal pathogens are risk factors for ONJ in cancer patients receiving intravenous BPs. To test our hypothesis and accomplish our goal, we plan to enroll 50 cancer patients receiving intravenous BP with ONJ and 100 controls (cancer patients on intravenous BP who have not developed ONJ) matched according to type of cancer, type of BP, duration of BP, age and sex.
Two specific aims will be pursued. (a) To determine the association between clinical and microbiological measures of periodontitis and risk of ONJ development. We will perform a thorough intraoral and periodontal exam in cases and matched controls to test if clinical measures of periodontitis are associated with ONJ. Further, we will also evaluate the prevalence of putative periodontal pathogens in subgingival plaque samples collected from these same cases and controls. (b) To determine whether ONJ is associated with increased mucosal invasion of putative periodontal pathogens and Actinomyces species. We will evaluate if putative periodontal pathogens and Actinomyces species colonize the oral mucosa cells near the ONJ lesion and contribute to its development. The findings will be used to define the role of periodontal disease in ONJ pathogenesis and contribute towards development of prevention and intervention strategies.

Public Health Relevance

Intravenous bisphosphonates are routine components of treatment protocols for multiple myeloma, and breast and prostate cancer patients with bone metastasis due to their ability to reduce cancer-induced destruction of bone. Osteonecrosis of the jaw is a recently identified devastating adverse effect of bisphosphonate treatment. In this exploratory proposal we will evaluate whether periodontal disease is a risk factor in osteonecrosis of jaw.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZDE1-VH (26))
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Wan, Jason
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University of Minnesota Twin Cities
Schools of Dentistry
United States
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Thumbigere-Math, Vivek; Michalowicz, Bryan S; Hughes, Pamela J et al. (2016) Serum Markers of Bone Turnover and Angiogenesis in Patients With Bisphosphonate-Related Osteonecrosis of the Jaw After Discontinuation of Long-Term Intravenous Bisphosphonate Therapy. J Oral Maxillofac Surg 74:738-46
Thumbigere-Math, V; Michalowicz, B S; de Jong, E P et al. (2015) Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw. Oral Dis 21:46-56
Thumbigere-Math, Vivek; Michalowicz, Bryan S; Hodges, James S et al. (2014) Periodontal disease as a risk factor for bisphosphonate-related osteonecrosis of the jaw. J Periodontol 85:226-33