Olejnik Cécile, Falgayrac Guillaume, During Alexandrine, Cortet Bernard, Penel Guillaume
Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Faculté de Chirurgie Dentaire, Place de Verdun, F-59000 Lille, France; Service d'Odontologie, Centre Abel Caumartin, CHRU de Lille, F-59000 Lille, France.
Université de Lille, EA 4490 PMOI, F-59000 Lille, France; Faculté de Chirurgie Dentaire, Place de Verdun, F-59000 Lille, France.
Bone. 2016 Aug;89:32-39. doi: 10.1016/j.bone.2016.05.002. Epub 2016 May 7.
Due to their inhibitory effects on resorption, bisphosphonates are widely used in the treatment of diseases associated to an extensive bone loss. Yet, little is known about bisphosphonates effects on newly-formed bone quality. In the present study, adult male Sprague-Dawley rats (n=80) with a bone defect calvaria area were used and short-term effects of zoledronic acid (ZA) were studied on the healing bone area. Three ZA treatments were tested by using either: 1°) a low single dose (120μgZA/kg, n=10; equivalent to human osteoporosis treatment), 2°) a low fractionated doses (20μgZA/kg daily for 6days either a total of 120μg/kg, n=15), and 3°) a high fractionated doses, (100μgZA/kg weekly for 6weeks, n=15; equivalent to 6months of human bone metastasis treatment). For each treatment, a control "vehicle" treatment was performed (with an identical number of rats). After ZA administration, the intrinsic bone material properties were evaluated by quantitative backscattered electron imaging (qBEI) and Raman microspectroscopy. Neither single nor fractionated low ZA doses modify the intrinsic bone material properties of the newly-formed bone compared to their respective control animals. On the opposite, the high ZA treatment resulted in a significant decrease of the crystallinity (-25%, P< 0.05) and of the hydroxyproline-to-proline ratio (-30%, P<0.05) in newly-formed bones. Moreover, with the high ZA treatment, the crystallinity was positively correlated with the hydroxyproline-to-proline ratio (ρ=0.78, P<0.0001). The present data highlight new properties for ZA on bone formation in a craniofacial defect model. As such, ZA at high doses disrupted the apatite crystal organization. In addition, we report here for the first time that high ZA doses decreased the hydroxyproline-to-proline ratio suggesting that ZA may affect the early collagen organization during the bone healing.
由于其对骨吸收的抑制作用，双膦酸盐被广泛用于治疗与广泛骨质流失相关的疾病。然而，关于双膦酸盐对新形成骨质量的影响知之甚少。在本研究中，使用成年雄性Sprague-Dawley大鼠（n = 80），其颅骨区域存在骨缺损，研究了唑来膦酸（ZA）对愈合骨区域的短期影响。通过以下三种方式测试了ZA治疗：1°）低单次剂量（120μg ZA/kg，n = 10；相当于人类骨质疏松症治疗剂量），2°）低分次剂量（每天20μg ZA/kg，共6天，总计120μg/kg，n = 15），以及3°）高分次剂量（每周100μg ZA/kg，共6周，n = 15；相当于人类骨转移治疗6个月的剂量）。对于每种治疗，均进行了对照“载体”治疗（大鼠数量相同）。给予ZA后，通过定量背散射电子成像（qBEI）和拉曼光谱对骨的固有材料特性进行评估。与各自的对照动物相比，低剂量的单次或分次ZA均未改变新形成骨的固有材料特性。相反，高剂量ZA治疗导致新形成骨的结晶度显著降低（-25%，P < 0.05）以及羟脯氨酸与脯氨酸比率显著降低（-30%，P < 0.05）。此外，在高剂量ZA治疗下，结晶度与羟脯氨酸与脯氨酸比率呈正相关（ρ = 0.78，P < 0.0001）。本研究数据突出了ZA在颅面缺损模型中对骨形成的新特性。因此，高剂量的ZA破坏了磷灰石晶体结构。此外，我们首次在此报告，高剂量ZA降低了羟脯氨酸与脯氨酸比率，表明ZA可能在骨愈合过程中影响早期胶原组织。
