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Bisphosphonates and Time to Osteonecrosis Development

^aHarvard School of Dental Medicine, Department of Oral Health Policy & Epidemiology, Boston, Massachusetts, USA; ^bTufts School of Dental Medicine, Department of Orthodontics, Boston, Massachusetts, USA; ^cColumbia College of Dental Medicine, Division of Oral Epidemiology & Biostatistics, New York, New York, USA; ^dHarvard School of Public Health, Department of Epidemiology, Boston, Massachusetts, USA

Key Words. Bisphosphonates • BONJ • Cancer • Dose • Osteoporosis • Time

Correspondence: Correspondence: Athanasios I. Zavras, D.M.S., M.S., Dr.M.S., Columbia College of Dental Medicine, 601 W. 168th St., New York, New York 10032, USA. Telephone: 212-342-0425; Fax: 212-342-8558; e-mail: az2256{at}columbia.edu

Received June 15, 2009; accepted for publication September 28, 2009.

Disclosures: Pinelopi Kleio Palaska: None; Vassiliki Cartsos: None; Athanasios I. Zavras: Consultant/advisory role: Research Triangle Institute; Research funding/contracted research: National Institute of Dental Craniofacial Research Grant No. DE018143.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is a complication of long-term bisphosphonate (BP) use. Given the beneficial effects of BP on bone quality in patients with cancer or osteoporosis, it is of great importance to understand the risk as it relates to time to event or cumulative dose until the onset of disease. Because there is no information on the lowest toxic dose from clinical trials, here we report on a review of 71 case series published since 2003. We calculated the weighted mean time to event, as well as the minimum reported time and dose for zoledronate, pamidronate, and oral bisphosphonates. The mean time to BONJ after zoledronate treatment was calculated at 1.8 years and the minimum was 10 months; after pamidronate, the mean time was 2.8 years and the minimum was 1.5 years; and after oral BP therapy, the mean time was 4.6 years and the minimum was 3 years. Zoledronic acid seems to be the most potent among the nitrogen-containing BPs. Factors that seem to affect BONJ and time to event were invasive dental procedures and other comorbid factors such as advanced age, rheumatoid arthritis, diabetes, use of corticosteroids, vitamin D deficiency, and more. Understanding the pathophysiology of the disease requires further research.