Jawbone Changes in Sodium Zoledronic Acid- and Dexamethasone-Treated Rats

Abstract

Previous studies have evaluated bisphosphonate-related osteonecrosis of the jaw (ONJ) after tooth extraction with concurrent administration of bisphosphonate zoledronic acid (ZOL) and steroids. However, details of jawbone changes after administration of ZOL and steroids without tooth extraction remain unclear. In this study, we administered ZOL and dexamethasone (DEX) in rats and compared changes in the jawbone with and without tooth extraction. The right maxillary first molar (M 1 ) was extracted from 8-week-old rats treated with ZOL, ZOL+DEX or DEX. The right maxillary M 1 region as the extraction sample and the left maxillary M 1 region as the non-extraction sample were compared with macroscopic, radiological, histologic and immunohistochemical examinations. In the extraction samples, we detected incomplete mucosal closure macroscopically and found ONJ on histological examination. In addition, immunohistochemical and threedimensional analysis of trabecular bone structure showed inhibition of remodeling and angiogenesis in the extraction samples. In the non-extraction samples, we observed inhibition of remodeling, reduced activity of osteoclasts and osteoblasts and suppression of angiogenesis. These findings demonstrate that ONJ can develop under the mucosa with ZOL and DEX treatment, even without invasive procedures. The data suggest that ZOL and DEX can induce ONJ in rats under both invasive and noninvasive conditions because ZOL suppresses osteoclast activity and DEX inhibits remodeling by suppressing osteoblast activity. The results also suggest that surgical stress, such as tooth extraction or bacterial infection, might lead to more severe bisphosphonaterelated ONJ.

Oral ulceration with bone sequestration: Retrospective study of eight cases and literature review

“…Literature review yielded 16 eligible original studies reporting 32 cases of OUBS, on June 15, 2018 (Table ). We excluded a conference abstract (Koshal, Chaudhry, Johnson, & Porter, ); two reviews (Farah & Savage, ; Palla et al, ); two case reports that we could not access (Danesh‐Meyer, ; Dhanrajani, ); two cases of bone sequestration developing in the interdental bone between upper molars due to the habitual use of a metallic pin (Aamir & Mandroli, ) or a toothpaste allergy (Sonnier & Horning, ), respectively, as they did not develop on a prominence of the jawbones; a case report of an ulcerated torus mandibularis, where the underlying bone was proved microscopically to be vital (Manganaro, Faulk‐Eggleston, Schanzer, & Dagostino, ); and three cases in patients medicated with drugs that may induce medication‐related osteonecrosis of the jaws (MRONJ) (Abel Mahedi Mohamed, Nielsen, & Schiodt, ; Aghaloo & Tetradis, ; Tezuka & Tanaka, ), as it is not possible to exclude that they may represent examples of spontaneous MRONJ. In contrast, we included a patient that developed bone sequestration two days after an intravenous infusion for the first time of 4 mg zoledronic acid (Almazrooa et al, ), as the short time interval makes the possibility of MRONJ improbable (Favia, Tempesta, Limongelli, Crincoli, & Maiorano, ; Katz & Ordoveza, ).…”

Investigation on the Action and Effect of Culture Supernatant of Human Dental Pulp Stem Cells Using Rats with Medication-Related Osteonecrosis of the Jaw

“…Bisphosphonate (BP) preparations are useful in treating osteoporosis, Paget disease of bone, bone metastasis of malignant tumors, multiple myeloma, and hypercalcemia, as well as in preventing and improving a range of bone-related conditions 1,2) . However, BP preparations tend to induce osteoclast (OC) apoptosis and suppress angiogenesis 3) . Although medication-related osteonecrosis of the jaw (MRONJ) has been reported as a symptom in association with BP preparations, a specific cure is yet to be established.…”