Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis
Evaluation of therapeutic effects of teriparatide in a rat model of zoledronic acid-induced bisphosphonate-related osteonecrosis
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DOI：
10.1016/j.ajoms.2019.03.001
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发表时间：
2019-09-01
影响因子：
0.4
通讯作者：
Tominaga, K.
中科院分区：
文献类型：
--
作者：
Ikeda, H.;Yoshiga, D.;Tominaga, K.
颌骨坏死是使用双膦酸类药物患者的一种并发症。在本研究中，我们旨在探讨特立帕帝(TPTD)对双磷酸盐相关性骨坏死(BRON)大鼠的作用及其机制。用唑来膦酸(ZOL)诱导大鼠骨坏死。注射ZOL四周后，大鼠接受了钻孔手术。这些洞里填满了冷冻干燥的放线菌伴生菌。4周后，TPTD或生理盐水(n=9)间断给药，持续4周。随后，对大鼠实施安乐死，并检测下颌骨和股骨的坏死量和骨再生情况。同时检测血清核因子-kappaB受体激活物(RANKL)、骨钙素(OC)和I型胶原C端交联末端肽(CTX)。TPTD能减少新生大鼠下颌骨和股骨的坏死骨面积，并诱导新骨形成。此外，TPTD注射还能增加破骨细胞的数量。其潜在的机制是TPTD诱导RANKL的蛋白水平。此外，TPTD注射组的血清骨代谢生物标志物(OC和CTX)水平升高。综上所述，ZOL对破骨细胞有负性作用。TPTD能有效消除ZOL的不良反应。TPTD在预防骨吸收、促进成骨方面有积极作用。此外，TPTD促进了破骨细胞的生成，进而导致了胚胎发育的改善。
Osteonecrosis of the jaw is a complication in patients using bisphosphonate agents. In this study, we aimed to investigate the effects and mechanism of teriparatide (TPTD) in a rat model of bisphosphonate-related osteonecrosis (BRON). Osteonecrosis was induced by administration of zoledronic acid (ZOL). Four weeks after ZOL injection, the rats underwent a surgery in which drilling holes were made. These holes were filled with freeze-dried Aggregatibacter actinomycetemcomitans. After the four-weeks period, TPTD or saline (n=9) was intermittently administered for four weeks. Later, rats were euthanized, and the mandible and femur bones were examined the amount of necrosis and bone regeneration. Serum receptor activator of NF-kappa B ligand (RANKL), osteocalcin (OC), and C-terminal crosslinking telopeptide of type I collagen (CTX) were also examined. TPTD administration reduced necrotic bone area of the mandibles and femurs in the BRON rat model and induced new bone formation. In addition, TPTD injection increased the number of osteoclasts. The suggested underlying mechanism is the induction of protein levels of RANKL by TPTD. Furthermore, the serum levels of bone metabolism biomarkers (OC and CTX) were upregulated in the TPTD injection group. In conclusion, ZOL has negative effects on osteoclasts. TPTD was found to be effective in eliminating the negative effects of ZOL. TPTD had positive effects in preventing bone resorption and promoting osteogenesis. In addition, TPTD improved osteoclastogenesis, which in turn led to the improvement of BRON.