Abstract
To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing. The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ.
Highlights
The bisphosphonates (BP) belong to a group of drugs commonly administered to treat benign bone disorders such as osteoporosis, osteogenesis imperfecta and Paget’s disease as well as solid malignant neoplasms involving bones, such as multiple myeloma[2]
The clinical features of Medication-related osteonecrosis of the jaw (MRONJ) may vary according to the patient clinical condition, their medical and dental background, drug administration time and method, but it is usually characterized by an exposure of jaw bone surrounded by oral mucosa with inflammatory signs and pain symptoms[6,7,8]
Forty-five male rats (Rattus norvegicus, albinus, Wistar), weighting about 250g were used in this study, and underwent the upper right central incisor tooth extraction were divided in two groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/ kg (Zometa, Novartis, Basel, Switzerland, 35μg/kg) into the tail vein every two weeks, according to Hokugo et al.[17]
Summary
The bisphosphonates (BP) belong to a group of drugs commonly administered to treat benign bone disorders such as osteoporosis, osteogenesis imperfecta and Paget’s disease as well as solid malignant neoplasms involving bones, such as multiple myeloma[2]. Despite the great benefits of BP in patients with benign or malignant conditions, an oral complication was observed arising from the use of this drug, especifically: Medication-related osteonecrosis of the jaw (MRONJ), which aroused attention from the medical and dental professionals. The clinical features of MRONJ may vary according to the patient clinical condition, their medical and dental background, drug administration time and method, but it is usually characterized by an exposure of jaw bone surrounded by oral mucosa with inflammatory signs and pain symptoms[6,7,8]. The interaction between bone metabolism, infection, local trauma and theories of bone remodeling suppression, antigenic effect and oral mucosa toxicity have been studied to elucidate its etiopathogenesis[2,12,13,14]
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