Potential pathophysiological mechanisms in osteonecrosis of the jaw

Abstract

Bisphosphonates are used in the treatment of hypercalcemia of malignancy, skeletal complications associated with metastastic bone disease, Paget's disease, and osteoporosis. Osteonecrosis of the jaw (ONJ) is a recently described clinical condition that has been associated with the use of nitrogen-containing bisphosphonates. Reports describing this entity first appeared in the literature in 2003. While there have been significant numbers of case reports and a limited number of retrospective and prospective studies examining risk factors associated with ONJ, the pathophysiology of this condition remains elusive. In this review, we explore proposed mechanisms underlying ONJ development and identify potential areas for future investigation.

Conflict of interest statement

Conflicts of Interest

The authors declare no conflicts of interest.

© 2011 New York Academy of Sciences.

Figures

Figure 1

Cellular proliferation of oral keratinocytes with pamidronate. Low concentrations of pamidronate (0.003–0.03 mM) did not affect cell proliferation over the course of seven days. A higher dose (0.1 mM) significantly inhibited proliferation. *P < 0.05 when compared to controls.

Figure 2

Caspase-3 activity in oral keratinocytes incubated with pamidronate. Pamidronate did not significantly increase caspase-3 activity in cells over a 48-h period when compared with controls. The positive control (+) was obtained by incubating cells with staurosporine and cycloheximide. * Significant increase compared with controls, P <0.05.

Figure 3

Wound healing in oral keratinocytes with pamidronate. Cells were observed for 96 h after wounding in cell culture plates. Control wells exhibited significant migration into the wounded area from time of injury (A) to 96 h (B). Cells preincubated for 72 hours with 0.1 mM pamidronate prior to wounding had greatly reduced migration from 0 (C) to 96 h (D). Data shown are representative of three independent experiments.

Figure 4

Cellular proliferation of human oral keratinocytes with pamidronate. Low concentrations of pamidronate (0.003–0.03 mM) did not affect cell proliferation over the course of seven days. A higher dose (0.06 mM and 0.1 mM) significantly inhibited proliferation. *P <0.05 when compared to controls.

Figure 5

Difference in cellular proliferation of human alveolar and long bone. Proliferation of long bone cells in culture was significantly less over the course of seven days compared with alveolar bone cells.