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评估模态阻尼因子作为骨质疏松症诊断工具及其与血清骨钙素和I型胶原N-端肽的关系,以监测阿仑膦酸钠对去卵巢大鼠的疗效。

Evaluation of modal damping factor as a diagnostic tool for osteoporosis and its relation with serum osteocalcin and collagen I N-telopeptide for monitoring the efficacy of alendronate in ovariectomized rats.

作者信息

Christopoulou G E, Stavropoulou A, Anastassopoulos G, Panteliou S D, Papadaki E, Karamanos N K, Panagiotopoulos E

机构信息

School of Medicine, Laboratory of Anatomy, and Department of Orthopedics, Patras University Hospital, University of Patras, Patras, Greece.

出版信息

J Pharm Biomed Anal. 2006 Jun 7;41(3):891-7. doi: 10.1016/j.jpba.2005.12.038. Epub 2006 Feb 20.

Abstract

Osteoporosis is a metabolic bone disease characterized by reduced bone mass and deterioration of bone microarchitecture. It results from the shift of the osteoblast-osteoclast activity equilibrium in favor of the later. Although, a number of biochemical markers, such as collagen I N-telopeptide (NTx) and osteocalcin (OC), have been used for monitoring bone remodeling, a new, monitoring, non-invasive method, which is based on the measurement of the dynamic characteristic of bone and is known as modal damping factor (MDF), has not been evaluated as a diagnostic tool for osteoporosis. Bisphosphonates, such as alendronate, have an established role in the treatment of osteoporosis. The aim of the present study was, therefore, to evaluate the effects of alendronate on the levels of MDF, serum NTx and OC on osteoporosis induced by ovariectomy in rats. Furthermore, the effects of alendronate on osteoporosis have been histologically evaluated. Fifteen adult female Wistar rats were bilaterally ovariectomized and osteoporosis was histologically confirmed and by the use of peripheral quantitative computerized tomography (pQCT). MDF was applied to assess the bone structural integrity. The serum levels of NTx (37.4+/-0.5 nM bone collagen equivalents, BCE) and OC (111.0+/-8.2 ng/mL) were found to significantly increase following ovariectomy (72.0+/-2.9 nM BCE and 213.5+/-12.1 ng/mL, respectively, p<0.001). As assessed by histology and the levels of NTx and OC in sera, animals treated with alendronate presented a statistically significant deceleration in the progression of the disease in comparison to the no-therapy control group (alendronate group NTx levels: 146.3+/-8.9 nM BCE versus no-therapy control group NTx levels: 265.3+/-14.0 nM BCE, p<0.001, alendronate group OC levels: 205.6+/-18.2 ng/mL versus no-therapy group OC levels: 353.9+/-26.1 ng/mL, p<0.001). Data obtained from the vibration analysis performed illustrated that the change in damping was equal or greater to the change in total and trabecular density, respectively. Damping increased with decreasing bone density, as expected, given that damping accounts for the structural integrity of bone (MDF value before ovariectomy: 0.058+/-0.003 versus MDF value after ovariectomy: 0.098+/-0.003, p<0.001). The higher damping values correspond to more deteriorated structures. In particular, both total and trabecular density were significantly decreased following ovariectomy (total density before ovariectomy: 702.4+/-19.0 versus total density after ovariectomy: 542.2+/-12.8, p<0.001, trabecular density before ovariectomy: 445.3+/-13.0 versus trabecular density after ovariectomy: 396.7+/-8.4, p<0.05). MDF value of the alendronate group (0.07+/-0.002) was significantly lower (p<0.001) as compared to MDF value after ovariectomy (0.098+/-0.003) and that of the no-therapy group (0.1+/-0.004, p<0.001). The administration of alendronate seemed to have no effect on either total or trabecular density, since both parameters continued to decrease (alendronate group total density: 549.4+/-12.3, alendronate group trabecular density: 368.4+/-14.7). However, when this was compared to the no-therapy group, a statistically significant difference of total density at the 0.05 level was observed (no-therapy total density: 464.8+/-9.1). The results of this study suggest that combined measurements of MDF, NTx and OC may be a potential diagnostic tool for osteoporosis and monitoring bone integrity during treatment with bisphosphonates. Furthermore, administration of alendronate showed to offer a critical deceleration in the progression of osteoporosis.

摘要

骨质疏松症是一种代谢性骨病,其特征为骨量减少和骨微结构退化。它是由成骨细胞 - 破骨细胞活性平衡向破骨细胞方向偏移所致。尽管一些生化标志物,如I型胶原N - 端肽(NTx)和骨钙素(OC),已被用于监测骨重塑,但一种基于测量骨动态特性的新型非侵入性监测方法——模态阻尼因子(MDF),尚未被评估作为骨质疏松症的诊断工具。双膦酸盐类药物,如阿仑膦酸钠,在骨质疏松症治疗中具有既定作用。因此,本研究的目的是评估阿仑膦酸钠对去卵巢大鼠骨质疏松症模型中MDF水平、血清NTx和OC的影响。此外,还对阿仑膦酸钠对骨质疏松症的影响进行了组织学评估。15只成年雌性Wistar大鼠双侧卵巢切除,通过组织学检查以及外周定量计算机断层扫描(pQCT)确认骨质疏松症。应用MDF评估骨结构完整性。去卵巢后血清NTx(37.4±0.5 nM骨胶原当量,BCE)和OC(111.0±8.2 ng/mL)水平显著升高(分别为72.0±2.9 nM BCE和213.5±12.1 ng/mL,p<0.001)。通过组织学以及血清中NTx和OC水平评估,与未治疗对照组相比,阿仑膦酸钠治疗组动物疾病进展出现统计学显著减缓(阿仑膦酸钠组NTx水平:146.3±8.9 nM BCE,未治疗对照组NTx水平:265.3±14.0 nM BCE,p<0.001;阿仑膦酸钠组OC水平:205.6±18.2 ng/mL,未治疗组OC水平:353.9±26.1 ng/mL,p<0.001)。振动分析数据表明,阻尼变化分别等于或大于总密度和小梁密度变化。正如预期,随着骨密度降低阻尼增加,因为阻尼反映了骨的结构完整性(去卵巢前MDF值:0.058±0.003,去卵巢后MDF值:0.098±0.003,p<0.001)。较高的阻尼值对应于更退化的结构。特别是,去卵巢后总密度和小梁密度均显著降低(去卵巢前总密度:702.4±19.0,去卵巢后总密度:542.2±12.8,p<0.001;去卵巢前小梁密度:445.3±13.0,去卵巢后小梁密度:396.7±8.4,p<0.05)。阿仑膦酸钠组MDF值(0.07±0.002)与去卵巢后MDF值(0.098±0.003)以及未治疗组MDF值(0.1±0.004)相比显著更低(p<0.001)。阿仑膦酸钠给药似乎对总密度或小梁密度均无影响,因为这两个参数持续降低(阿仑膦酸钠组总密度:549.4±12.3,阿仑膦酸钠组小梁密度:368.4±14.7)。然而,与未治疗组相比,在0.05水平观察到总密度有统计学显著差异(未治疗组总密度:464.8±9.1)。本研究结果表明,联合测量MDF、NTx和OC可能是骨质疏松症的潜在诊断工具,并可用于双膦酸盐治疗期间监测骨完整性。此外,阿仑膦酸钠给药显示出能显著减缓骨质疏松症的进展。

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