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

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• 作者：Luis A. Có ; rdova^a ; ^b ; ^c ; ^{lcordova@stanford.edu" class="auth_mail" title="E-mail the corresponding author} ; Florian Guilbaud^a ; ^b ; ^{florian.guilbaud@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Jé ; rô ; me Amiaud^a ; ^b ; ^{jerome.amiaud@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Sé ; verine Battaglia^a ; ^b ; ^{severine.battaglia@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Cé ; line Charrier^a ; ^b ; ^{celine.charrier@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Fré ; dé ; ric Lezot^a ; ^b ; ^{frederic-lezot@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Benoî ; t Piot^d ; ^e ; ^{benoit.piot@chu-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Franç ; oise Redini^a ; ^b ; ^{francoise.redini@univ-nantes.fr" class="auth_mail" title="E-mail the corresponding author} ; Dominique Heymann^a ; ^b ; ^e ; ^f ; ^{dominique.heymann@sheffield.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Osteonecrosis of the jaw ; Zoledronic acid ; Osteoclast ; Osteoblast ; Alveolar bone ; Basic multicellular unit
• 刊名：Journal of Cranio-Maxillofacial Surgery
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：44
• 期：9
• 页码：1387-1394
• 全文大小：1607 K

文摘

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 μg/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.