Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis
Decreased bone tissue mineralization can partly explain subchondral sclerosis observed in osteoarthritis
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DOI：
10.1016/j.bone.2012.01.024
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发表时间：
2012-05-01
期刊：
影响因子：
4.1
通讯作者：
Ito, K.
中科院分区：
文献类型：
--
作者：
Cox, L. G. E.;van Donkelaar, C. C.;Ito, K.
多年来，骨关节炎（OA）的药物治疗主要集中在软骨上。然而，有理论认为，骨变化，如骨体积分数增加和骨基质矿化减少可能在OA的发生和发病机制中也起重要作用。骨变化背后的机制是争论的主题，更好的理解可能有助于骨靶向OA治疗的发展。在文献中，骨体积分数的增加被假设是由于机械调节的骨适应性对矿化减少的反应。此外，据报道，骨体积分数和矿化的变化在软骨附近最高，并且据报道，骨体积分数与软骨退化相关。这些数据表明，软骨退变，骨体积分数，骨基质矿化可能与OA。在本研究中，我们的目的是调查之间的关系，软骨退变，骨基质矿化和骨体积分数在局部水平。利用microCT，我们确定了骨基质矿化和骨体积分数作为与软骨距离的函数，这些距离来自具有不同程度软骨退化的人OA胫骨平台的骨软骨栓塞。此外，我们还评估了骨基质矿化减少引起的机械调节性骨适应是否可能是OA患者骨体积分数增加的原因。为此，我们使用实验获得的矿化数据作为骨适应模拟的输入。我们模拟了不同矿化程度下机械调节骨适应的效果，并将模拟结果与实验数据进行了比较。我们发现，局部的变化，软骨下骨矿化和骨体积分数只发生在严重退化的软骨下，表明骨矿化和体积分数与软骨退化在局部水平。此外，实验数据和模拟均表明，骨体积分数的深度依赖性增加可能是由骨基质矿化减少引起的。然而，定量比较表明，矿化减少只能解释OA中观察到的部分软骨下硬化。(C)2012 Elsevier Inc. All rights reserved.
For many years, pharmaceutical therapies for osteoarthritis (OA) were focused on cartilage. However, it has been theorized that bone changes such as increased bone volume fraction and decreased bone matrix mineralization may play an important role in the initiation and pathogenesis of OA as well. The mechanisms behind the bone changes are subject of debate, and a better understanding may help in the development of bone-targeting OA therapies. In the literature, the increase in bone volume fraction has been hypothesized to result from mechanoregulated bone adaptation in response to decreased mineralization. Furthermore, both changes in bone volume fraction and mineralization have been reported to be highest close to the cartilage, and bone volume fraction has been reported to be correlated with cartilage degeneration. These data indicate that cartilage degeneration, bone volume fraction, and bone matrix mineralization may be related in OA. In the current study, we aimed to investigate the relationships between cartilage degeneration, bone matrix mineralization and bone volume fraction at a local level. With microCT, we determined bone matrix mineralization and bone volume fraction as a function of distance from the cartilage in osteochondral plugs from human OA tibia plateaus with varying degrees of cartilage degeneration. In addition, we evaluated whether mechanoregulated bone adaptation in response to decreased bone matrix mineralization may be responsible for the increase in bone volume fraction observed in OA. For this purpose, we used the experimentally obtained mineralization data as input for bone adaptation simulations. We simulated the effect of mechanoregulated bone adaptation in response to different degrees of mineralization, and compared the simulation results to the experimental data. We found that local changes in subchondral bone mineralization and bone volume fraction only occurred underneath severely degenerated cartilage, indicating that bone mineralization and volume fraction are related to cartilage degeneration at a local level. In addition, both the experimental data and the simulations indicated that a depth-dependent increase in bone volume fraction could be caused by decreased bone matrix mineralization. However, a quantitative comparison showed that decreased mineralization can only explain part of the subchondral sclerosis observed in OA. (C) 2012 Elsevier Inc. All rights reserved.