Established Periodontitis Acclerates Onset of Osteonecrosis of the Jaw

Objectives: Zoledronate (ZOL) is associated with medication-related osteonecrosis of the jaw (MRONJ). Periodontitis (PD) is a risk factor for MRONJ development. We previously established a dose relationship between ZOL and MRONJ in rice rats (Oryzymus palustris), an animal that develops age-related PD, when ZOL is begun at age 4-wks. We hypothesize that starting ZOL after mild to moderate PD is established (age 16 or 22 wks) accelerates MRONJ onset, compared to starting ZOL before PD is established (age 4 wks).
Methods: Rats ate standard (N=183, STD) or high-sucrose-casein (N=192, HSC) diet to induce either localized food-impaction-associated, or generalized PD, respectively. Then, rats were given 0 or 80µg/kg intravenous ZOL monthly, starting at ages 4- (no PD), 16- (mild PD), or 22-wks (moderate PD). 80µg/kg ZOL is the rat equivalent of the human ZOL oncology dose. Rats were necropsied after 6, 12, or 18 weeks (N=12-17/grp) of ZOL. High-resolution photos of all jaw quadrants were examined by three blinded observers to diagnose gross MRONJ. Histopathological analysis of lesions is underway.
Results: Starting ZOL in rats without PD (4-wks) caused 0,17, and 0% MRONJ prevalence in HSC rats after 6,12, and 18-wks ZOL; and 25% and 50% MRONJ prevalence in STD rats after 12 and 18 wks, respectively. Initiating ZOL in rats with mild PD (16-wks) caused 75% and 13% MRONJ prevalence in HSC rats after 6 and 12 wks; and 31% and 27% MRONJ prevalence in STD rats after 6 and 12 wks, respectively. Starting ZOL in rats with moderate PD (age 22-wks) caused 0% and 29% MRONJ prevalence in HSC rats after 6 and 12 wks; and MRONJ prevalence of 19% and 33% in STD rats after 6 and 12 weeks, respectively
Conclusions: Initiating ZOL in rice rats with established mild/moderate PD accelerates onset of MRONJ.