Bisphosphonates and Dexamethasone Suppress the Bone Turnover

doi:10.3969/j.issn.1005-4979.2013.06.002

Abstract

Abstract: Objective: To evaluate the impact of bisphosphonates and dexamethasone on the bone remodeling process of maxilla and cheekbone after injury. Methods: 60 female wild-type C57BL6 mice aged 8-10 weeks were split into two groups. The right first maxillary molar was extracted and an artificial invasive bone nest was made in the cheekbone of each mice. The experimental group was treated with zoledronate and dexamethasone intraperitoneally, while the control group received only PBS till the different time points of 1 day, 3 weeks and 8 weeks respectively after trauma. After euthanized, properties of the injured sites were assessed using micro-computed tomography(micro-CT), histopathology and immunohistochemistry analysis, and high performance liquid chromatography-mass spectrometric(LC-MS) methods. Results: Suppression of bone remodeling occurred both in the maxilla and cheekbone after injury, including empty osteocyte lacunae, sequestra, inflammation, radiopaque alveolar bone and irregular trabeculae. The zoledronate content absorbed by maxilla was much higher than that of cheekbone(P<0.05). Conclusions: The bone remodeling processes of maxilla and cheekbone after injury were both suppressed by bisphosphonates and dexamethasone.

Key words: bisphosphonates, bone remodeling, osteonecrosis, jaws, mice

摘要： 目的：研究双膦酸盐（BPs）和地塞米松联合应用对颌骨和颧骨创伤后骨改建的影响。方法：60只8～12周龄雌性C57BL6小鼠，每周2次腹腔注射唑来膦酸和地塞米松，以腹腔注射缓冲液为对照组。1周后将小鼠右上颌第一磨牙拔除，右侧颧骨制造骨创伤，后继续给药分别至术后第1天、第3周和第8周。小鼠安乐死后，取颌骨和颧骨，经不同处理后进行Micro?鄄CT扫描、HE染色、免疫组织化学染色、质谱?鄄色谱联用检测。结果：经双膦酸盐联合地塞米松处理后，颌骨和颧骨的骨改建均被抑制，出现骨细胞凋亡、辐射不透性死骨形成、炎症反应、骨小梁形态紊乱等现象，同时颌骨沉积的唑来膦酸的含量明显高于颧骨（P<0.05）。结论：双膦酸盐和地塞米松联合应用，可引起小鼠颌骨和颧骨创伤后的骨改建被抑制。

关键词: 双膦酸盐； , 骨改建； , 骨坏死； , 颌骨； , 小鼠

CLC Number:

R782.4

FENG Mu，SU Jian-sheng. Bisphosphonates and Dexamethasone Suppress the Bone Turnover[J]. 《Journal of Oral and Maxillofacial Surgery》, 2013, 23(6): 409-413.

冯沐，苏俭生. 双膦酸盐联合地塞米松对小鼠颌骨和颧骨创伤后骨改建的影响[J]. 《口腔颌面外科杂志》, 2013, 23(6): 409-413.

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URL: https://journal06.magtech.org.cn/Jweb_joms/EN/10.3969/j.issn.1005-4979.2013.06.002

https://journal06.magtech.org.cn/Jweb_joms/EN/Y2013/V23/I6/409

References

[1] Smith R, Russell RG, Bishop M. Diphosphonates and Page's disease of bone [J]. Lancet, 1971, 1(7706): 945-947.

[2] Paterson AD, Kanis JA, Cameron EC, et al. The use of dichloromethylene diphosphonate for the management of hypercalcaemia in multiple myeloma [J]. Br J Haematol, 1983, 54(1): 121-132.

[3] van Breukelen FJ, Bijvoet OL, van Oosterom AT. Inhibition of osteolytic bone lesions by (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.) [J]. Lancet, 1979, 1(8120): 803-805.

[4] Eastell R, Walsh JS, Watts NB, et al. Bisphosphonates for postmenopausal osteoporosis [J]. Bone, 2011, 49(1): 82-88.

[5] Reid IR. Bisphosphonates in the treatment of osteoporosis: a review of their contribution and controversies [J]. Skeletal Radiol, 2011, 40(9): 1191-1196.

[6] Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic [J]. J Oral Maxillofac Surg, 2003, 61(9): 1115-1117.

[7] Ruggiero SL, Dodson TB, Assael LA, et al. American Association of Oral and Maxillofacial Surgeons position paper: Bisphosphonate-Related Osteonecrosis of the jaws--2009 update: the need to refine the BRONJ definition [J]. J Oral Maxillofac Surg, 2009, 67(12): 2698-2699.

[8] Siddiqi A, Payne AG, Zafar S. Bisphosphonate-induced osteonecrosis of the jaw: a medical enigma [J]? Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2009, 108(3): e1-8.

[9] Bi Y, Gao Y, Ehirchiou D, et al. Bisphosphonates cause osteonecrosis of the jaw-like disease in mice [J]. Am J Pathol, 2010, 177(1): 280-290.

[10] Sonis ST, Watkins BA, Lyng GD, et al. Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients [J]. Oral Oncol, 2009, 45(2): 164-172.

[11] Pautke C, Kreutzer K, Weitz J, et al. Bisphosphonate related osteonecrosis of the jaw: A minipig large animal model [J]. Bone, 2012, 51(3): 592-599.

[12] Fournier P, Boissier S, Fileur S, et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone stimulated vascular regrowth in the ventral prostate in castrated rats [J]. Cancer Res, 2002, 62(22): 6538-6544.

[13] Odvina CV, Zerwekh JE, Rao DS, et al. Severely suppressed bone turnover：a potential complication of alendronate therapy [J]. J Clin Endocrinol Metab, 2005, 90(3): 1294-1301.

[14] Arranz Caso JA, Flores Ballester E, Ngo Pombe S, et al. Bisphosphonate related osteonecrosis of the jaw and infection with Actinomyces [J]. Med Clin, 2012, 139(15): 676-680.

[15] Polizzotto MN, Cousins V, Schwarer AP. Bisphosphonate-associated osteonecrosis of the auditory canal [J]. Br J Haematol, 2006, 132(1): 114.

[16] Mavrokokki T, Cheng A, Stein B, et al. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia [J]. J Oral Maxillofac Surg, 2007, 65(3): 415-423.

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