RANKL/OPG signaling affects the bone structure in rat model of mandibular osteoradionecrosis

Abstract

Objective: Osteoradionecrosis (ORN) of the jaws is an important side effect of head and neck cancer radiotherapy. The main objective of this work was to evaluate the expression of RANK, RANKL and OPG proteins, markers of bone remodeling, in rats submitted to radiotherapy. Material and Methods: Six-month-old male Wistar rats were divided into two groups: Irradiated group (IR), which received a single dose of 20 Gy in the jaw and after seven days had their three left mandibular molars extracted; Control group (C), which didn’t receive radiation, but underwent the same procedures. Twenty one days after the dental extractions, the animals were euthanized and their mandibles were removed for analysis. The volume density (Vv) of immunoexpression of RANK/RANKL/OPG was quantified by stereology. The bone volume ratio (BV/TV), the trabecular thickness (Tb.Th), the trabecular separation (Tb.Sp) and the trabecular number (Tb.N) were analyzed by microtomography (Micro-CT). Results: Vv of immunoexpression of RANKL and OPG were, respectively, 53% higher and 50% lower in IR animals compared to C group (p<0.05). Micro-CT showed that in the IR animals there was a reduction of the bone mass compared to the C animals. BV/TV and Tb.Th were 33% and 38% lower, respectively, in the IR animals (p<0.05), while Tb.Sp was 37.5% higher in these animals (p<0.05). Conclusions: Ionizing irradiation in a single high dose, followed by dental extractions promoted ORN in mandibular bone in rats, together with changes in the markers of bone remodeling RANK and OPG.