Severe compromise of preosteoblasts in a surgical mouse model of bisphosphonate-associated osteonecrosis of the jaw

Abstract

Objectives: The effect of amino-bisphosphonates on osteoblastic lineage and its potential contribution to the pathogenesis of bisphosphonate-associated osteonecrosis of the jaw (BONJ) remain controversial. We assessed the effects of zoledronic acid (ZOL) on bone and vascular cells of the alveolar socket using a mouse model of BONJ. Material and methods: Thirty-two mice were treated twice a week with either 100 mu g/kg of ZOL or saline for 12 weeks. The first left maxillary molar was extracted at the third week. Alveolar sockets were assessed at both 3 weeks (intermediate) and 9 weeks (long-term) after molar extraction by semi quantitative histomorphometry for empty lacunae, preosteoblasts (Osterix), osteoclasts (TRAP), and pericyte-like cells (CD146). Also, the bone microarchitecture was assessed by micro-CT. Results: Osteonecrotic-like lesions were observed in 21% of mice. Moreover, a decreased number of preosteoblasts contrasted with the increased number of osteoclasts at both time points. In addition, osteoclasts display multinucleation and detachment from the endosteal surface. Furthermore, the number of pericyte-like cells increased at the intermediate time point. The alveolar bone mass increased exclusively with long-term ZOL treatment. Conclusion: The severe imbalance between bone-forming cells and bone-resorbing cells shown in this study could contribute to the pathogenesis of BONJ

Borate bioactive glass prevents zoledronate‐induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis

“…Consistent with the results of many other studies, the actions of ZOL (Exp + Saline group) were not restricted exclusively to osteoclasts in the present work (Basso et al, 2013;Córdova et al, 2016).…”

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

“…The majority of previous studies reported the use of ZA via IP (intraperitoneal) or IV (intravenous) administration as an antiresorptive medication of choice for inducing MRONJ lesions in mice [15,17,24,25,27,29,30,32,33,35,37,39,[42][43][44][45][46], considering its higher potency when compared to other IV or oral nBP's [47]. Moreover, all mouse studies presented in S1 Table were performed in young or adult animals (age varying from 6 to 16 weeks old).…”

Efeito da terapia de longa duração com ácido zoledrônico no osso esponjoso da mandíbula e fêmur de ratos Wistar

“…Até o presente momento, a maioria dos estudos pré-clínicos que investigaram as alterações ósseas induzidas pelos BF em modelos animais, avaliaram as regiões dos alvéolos após a exodontia em modelos de OMAB (JABBOUR et al, 2014;CORDOVA et al, 2016).…”

“…Em concordância com os achados desta investigação, estudos anteriores demonstraram que a administração de AZ aumentou a densidade óssea na mandíbula (JABBOUR et al, 2014;CORDOVA et al, 2016). No entanto, esses estudos avaliaram o volume ósseo no alvéolo pós-extração de modelos animais de OMAB, onde o processo de reparo, a inflamação e a própria doença podem influenciar os resultados (JABBOUR et al, 2014;CORDOVA et al, 2016).…”

“…No entanto, esses estudos avaliaram o volume ósseo no alvéolo pós-extração de modelos animais de OMAB, onde o processo de reparo, a inflamação e a própria doença podem influenciar os resultados (JABBOUR et al, 2014;CORDOVA et al, 2016).…”