Bisphosphonates are the most common treatment for osteoporosis. In the last few years, increasing reports of osteonecrosis of the jaw (ONJ) have raised considerable concerns regarding the long-term safety of these agents. The case reports have created considerable uncertainty with patients and clinicians regarding the optimal pharmacotherapy for osteoporosis. Osteonecrosis of the jaw presents as a painful or painless area of exposed and sometimes infected bone in the oral cavity. Its morbidity, cost, and ideal treatment are not well understood. This R21 revised grant proposal will utilize the statistical power of large health care utilization databases to estimate the incidence of ONJ among users of bisphosphonates without cancer. All ONJ cases among a cohort of typical adults without cancer will be confirmed with primary chart review. Important subgroups of patients will be assessed including patients with prior dental extractions or infections, concomitant use of glucocorticoids, and specific comorbid illnesses. The clinical course and health care expenditures associated with ONJ will be assessed through chart review and analysis of the health care utilization database. Data from the confirmed cases of ONJ will form one of the largest collected case series of this condition, allowing assessment of the effectiveness of different treatment strategies for ONJ. Information from this proposal will answer immediate questions about the association between bisphosphonates and ONJ and will provide important data that can be used in designing future treatment trials for this condition.

Public Health Relevance

The proposed research will estimate the incidence and relative risk of osteonecrosis of the jaw among bisphosphonate users with osteoporosis. Millions of Americans have osteoporosis and many of them are using bisphosphonates for this condition. Pharmacotherapy for osteoporosis may be substantially affected through a better understanding of risks associated with this group of medications.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZDE1-RW (05))
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Wan, Jason
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Brigham and Women's Hospital
United States
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Gedmintas, L; Wright, E A; Dong, Y et al. (2017) Factors associated with fractures in HIV-infected persons: which factors matter? Osteoporos Int 28:239-244
Najm, M S; Solomon, D H; Woo, S-B et al. (2014) Resource utilization in cancer patients with bisphosphonate-associated osteonecrosis of the jaw. Oral Dis 20:94-9
Kim, Seoyoung C; Liu, Jun; Solomon, Daniel H (2014) The risk of atrial fibrillation in patients with rheumatoid arthritis. Ann Rheum Dis 73:1091-5
Gedmintas, Lydia; Wright, Elizabeth A; Losina, Elena et al. (2014) Comparative risk of fracture in men and women with HIV. J Clin Endocrinol Metab 99:486-90
Kim, Seoyoung C; Yelin, Ed; Tonner, Chris et al. (2013) Changes in use of disease-modifying antirheumatic drugs for rheumatoid arthritis in the United States during 1983-2009. Arthritis Care Res (Hoboken) 65:1529-33
Kim, Seoyoung C; Schmidt, Bernhard M W; Franklin, Jessica M et al. (2013) Clinical and health care use characteristics of patients newly starting allopurinol, febuxostat, and colchicine for the treatment of gout. Arthritis Care Res (Hoboken) 65:2008-14
Solomon, D H; Mercer, E; Woo, S B et al. (2013) Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int 24:237-44
Gedmintas, Lydia; Solomon, Daniel H; Kim, Seoyoung C (2013) Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. J Bone Miner Res 28:1729-37
Mercer, E; Norton, T; Woo, S et al. (2013) Ninety-one osteoporosis patients affected with bisphosphonate-related osteonecrosis of the jaw: a case series. Calcif Tissue Int 93:241-8
Kim, Seoyoung C; Landon, Joan E; Solomon, Daniel H (2013) Clinical characteristics and medication uses among fibromyalgia patients newly prescribed amitriptyline, duloxetine, gabapentin, or pregabalin. Arthritis Care Res (Hoboken) 65:1813-9

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