Abstract
Objectives This study aimed to assess the effect of zoledronic acid on an immunocompromised mice model with periapical disease. Materials and Methods Thirty C57BL/6N mice were randomly divided into three groups (N = 10). All animals were subjected to bilateral ovariectomy (OVX) and then treated with saline (Veh), zoledronic acid (ZA), or concomitant zoledronic acid and dexamethasone (ZA/Dx) for 12 weeks. Eight weeks after starting drug administration, pulpal exposure was conducted on the lower left first molar. Four weeks after pulpal exposure, all mice were sacrificed and the mandibles were collected for radiological and histological examinations. Results Microcomputed tomography (μ-CT) examination showed significantly reduced periapical bone resorption in the ZA/Dx group and decreased periodontal bone resorption in both ZA and ZA/Dx groups. Higher bone mineral density (BMD) and strengthened microstructure were found in ZA and ZA/Dx groups. More empty lacunae were found in ZA and ZA/Dx groups. Conclusions Apical periodontitis aggravates MRONJ under immunocompromised circumstances. Concurrent use of ZA and steroids inhibits alveolar bone resorption but increases the risk of developing MRONJ.
Highlights
Medication-related osteonecrosis of the jaw (MRONJ) is an intractable clinical situation characterized by necrotic bone exposure in the oral cavity that does not heal for more than 8 weeks
We have recently developed a modified rodent model demonstrating intracortical and trabecular remodeling of the jawbones following a bilateral ovariectomy, mimicking the intracortical remodeling process of humans. e present study aimed to investigate the relevance of periapical diseases in MRONJ using an immunocompromised mouse model with ovariectomy
Inflammatory response was observed in areas adjacent to the interradicular bone where bone resorption occurred and in regions near osteonecrosis which is characterized by substantial amounts of empty lacunae (Figure 7). e inflammatory response can be categorized into acute inflammation and chronic inflammation. e acute inflammation was graded as mild, moderate, and intense according to the extent of PMN. e chronic inflammation shown as plasma cells and/ or lymphocytes presenting in the specimen was observed
Summary
Medication-related osteonecrosis of the jaw (MRONJ) is an intractable clinical situation characterized by necrotic bone exposure in the oral cavity that does not heal for more than 8 weeks. Around 60–70% cases of MRONJ are associated with tooth extraction, where periapical diseases play a major role, resulting in the extraction. E majority of MRONJ cases occur in cancer patients, who may have compromised immune status. Some cancers such as multiple myeloma require a concomitant course of dexamethasone and zoledronic acid (ZA). Considering the vast number of patients under bisphosphonates treatment and the high incidence of periapical diseases, any further understanding of the role of periapical infections in the development of MRONJ is of crucial clinical significance to prevent and treat this disease. E present study aimed to investigate the relevance of periapical diseases in MRONJ using an immunocompromised mouse model with ovariectomy We have recently developed a modified rodent model demonstrating intracortical and trabecular remodeling of the jawbones following a bilateral ovariectomy, mimicking the intracortical remodeling process of humans. e present study aimed to investigate the relevance of periapical diseases in MRONJ using an immunocompromised mouse model with ovariectomy
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