Bisphosphonates and Time to Osteonecrosis Development

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Evaluate the current state of knowledge regarding risk of osteonecrosis of the jaw as it relates to dose and duration of intravenous bisphosphonates.Explain the concept of risk assessment in the context of preventing the development of osteonecrosis of the jaw.Describe the pathophysiology of ONJ and outline contributing factors such as invasive dental procedures, comorbidities, concomitant medications, vitamin D deficiency and/or hyperparathyroidism, certain genotypes, smoking, and the role of obesity. This article is available for continuing medical education credit at CME.TheOncologist.com. 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.