Professor of Biological Sciences, Aerospace and Mechanical Engineering, and Anthropology
University of Notre Dame
Animal model of osteonecrosis of the jaw related to bisphosphonate therapy for bone cancer
Bone resorption inhibitors, including bisphophonates (BPs), are the primary tools for managing bone cancer. BPs are highly effective in reducing bone pain, hypercalcemia and fractures for patients with metastatic bone disease from multiple myeloma or solid tumors (breast and prostate carcinoma). Clinical data have revealed a serious adverse event in patients receiving BP therapy, osteonecrosis of the jaw (ONJ). ONJ is manifested by poor oral wound healing (often following invasive dental procedures), gingival breakdown, and exposure and subsequent necrosis of subjacent oral bone. This chronic ailment affects cancer patients on antiresorptive therapy, especially intravenous BPs. The demographics of an aging population, coupled with a prevalence of breast, prostate and bone cancer in older humans, portend the likelihood of greater BP use and increases in ONJ. Early stages of ONJ are difficult to diagnose and there is no effective treatment for advanced ONJ
In collaboration with the Niebur and Ovaert labs at Notre Dame, research in the Ravosa lab is developing a comprehensive animal model of ONJ that can help identify which BP patients are at risk for ONJ. We are employing a hierarchical, multifaceted approach to assess the effects of BP therapy and oral trauma on mandibular bone remodeling, structure, microdamage and mechanical properties as well as the viability, apoptosis and wound healing capability of oral gingiva. This research involves multiple levels of trainees, including undergraduates, graduate students and postdoctoral fellows. In examining the early pathogenesis of ONJ, the ultimate goal of our quantitative imaging, cell biological and engineering analyses is to develop early detection and treatment strategies for preventing a debilitating disease related to standard clinical care for secondary bone cancer metastases.