Medication-related osteonecrosis of the jaw, osteoradionecrosis, and osteomyelitis: A comparative histopathological study

Abstract

It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.

Medication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: Microtomographic, histological and immunohistochemical characterization

“…Additionally, an increased quantity of empty lacunae was found in the ZA E site compared to Control E site (Fig 4). Empty lacunae is one diagnostic factor for osteonecrosis [12, 13] and is consistent with other findings in mice MRONJ lesions [23]. Interestingly, the greatest amount of empty lacunae was found at E sites, but not in the NE sites in ZA-treated mice (S2 Fig).…”

“…In our histopathological analysis, 100% of our ZA treated mice presented a delayed bone healing and MRONJ lesions histological characteristics (Figs 4 and 5). These compare with other findings in mice [23, 39], rats [61, 62, 64] and humans [12, 13], including intense leukocyte infiltration, areas of non-vital bone and discrete bone sequestrum.…”

“…This finding highlights a hindrance to bone repair processes in which, under normal circumstances, osteocytes undergo apoptosis and recruit osteoclasts to resorb damaged bone [66]. Furthermore, it emphasizes that trauma is crucial for osteocyte apoptosis, which is a hallmark characteristic of necrotic bone [12, 13].…”

“…MRONJ human biopsies exhibit empty osteocyte lacunae, lack of osteoblasts along new bone, and detached osteoclasts. MRONJ biopsy samples are frequently associated with a secondary infection [12, 13], and may exhibit similar histological characteristics to osteomyelitis and osteoradionecrosis [13]. Previous studies have explored MRONJ animal models to provide explanations for the disease process.…”

Immediate hyperbaric oxygen after tooth extraction ameliorates bisphosphonate‐related osteonecrotic lesion in rats

“…Our study also showed similar results where the inflamed connective tissue was exposed without the epithelial coverage, thin trabeculae was lined with rare multinuclear osteoclasts, and marrow spaces infiltrated with the inflammatory cells detected in the alveolar bones in our animal MRONJ‐like lesions. However, the histological feature of MRONJ may overlap with osteomyelitis . MRONJ may be considered as an adverse drug reaction consisting of progressive bone destruction in the maxillofacial region under current or previous treatment with antiresorptive and antiangiogenic medications, exposed bone, and no history of radiation therapy or obvious metastatic disease to the jaws .…”