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骨-植入物界面中的锶

Strontium in the bone-implant interface.

作者信息

Vestermark Marianne Toft

机构信息

Orthopaedic Research Laboratory, Aarhus University Hospital, Norrebrogade 44, Aarhus C, Denmark.

出版信息

Dan Med Bull. 2011 May;58(5):B4286.

Abstract

Total hip replacement surgery is being performed on an increasingly large part of the population and at increasingly younger age. Because we live and stay physically active longer, and since hip replacement surgery has become quite successful, the treatment is being offered to progressively more patients. Unfortunately, about 17% of hip replacement surgeries currently involve revisions. Consequently, the longevity of both the primary and revision implant is an issue and warrants further investigation. Implants undergoing early instability or even subsidence correlate with an increased risk of aseptic loosening, subsequently requiring revision. Thus, the goal is early fixation by osseointegration of the implant. For revision implants, this is an even greater challenge since an allograft is often needed during surgery to obtain immediate stability of the implant. Bone grafts are rapidly resorbed. Thus, instability of the prosthesis may develop before new bone formation is well established and can mechanically secure the prosthesis. Strontium is a dual action drug; being both bone anabolic and anti-catabolic. In the form of strontiumranelate, it is used in the treatment of osteoporosis. Strontium may potentially improve the early osseointegration and fixation of implants. This dissertation consists of three studies investigating the effect of strontium at the bone-implant interface. The questions were firstly, what is the optimal delivery method for strontium to the interface, and secondly, can strontium exercise its dual action at the interface? The studies were performed in a cementless, experimental gap model in canine. The effects of strontium were evaluated by histomorphometrical analysis of the osseointegration and mechanical push-out test of implant fixation. Different stereological methods were used for the histomorphometrical analysis of each study. The methods used were reviewed critically and found valid. Study I compared a 5% strontium-substituted hydroxyapatite (HA) coating with an HA coating after 4 weeks and 12 weeks observation time. We examined whether fixation of the implant was improved by the strontium substitution. It was found that fixation of the implant was not improved by the strontium substituted HA coating at any of the two time points. Study II compared a 5% strontium-doped HA bone graft extender with an HA bone graft extender. The bone graft extender was mixed with allograft and impacted around a titanium implant. The objective of this study was to determine whether strontium doping of the bone graft extender could protect the allograft from fast resorption and increase gap healing, leading to the improved fixation of the implant. We found that the strontium doping increased gap healing and protected the allograft, however, results of the mechanical test were inconclusive. The reason might have been that the increased gap healing had not yet reached the implant during the 4 weeks observation time, so ongrowth onto the implant was not improved. Study III investigated the effects of bioactive glass coating with a 0%, 10% or 50% strontium-substitution versus HA coating of grit-blasted titanium alloy implants. The goal was to determine whether fixation of the implant would be improved by the bioactive glass coating, and then further improved by the strontium-substitution of the coating in a dose-dependent manner. Unfortunately, the bioactive glass coating failed, presumably due to aluminum contamination originating from the grit-blasting powder. The HA coated implants were superior in all parameters of osseointegration and the mechanical fixation of the implants. These studies show the importance of performing further experimental investigation. Even when investigating a known agent for use in a new application. Strontium delivered as doping of an HA bone graft extender showed potential as a dual acting agent in the interface. However, delivery methods of strontium to the bone-implant interface clearly need further investigation.

摘要

全髋关节置换手术在越来越多的人群中开展,且患者年龄越来越小。因为我们的寿命延长且保持身体活跃的时间更长,同时髋关节置换手术已相当成功,所以越来越多的患者接受了这种治疗。不幸的是,目前约17%的髋关节置换手术需要翻修。因此,初次植入物和翻修植入物的使用寿命都是问题,值得进一步研究。经历早期不稳定甚至下沉的植入物与无菌性松动风险增加相关,随后需要进行翻修。因此,目标是通过植入物的骨整合实现早期固定。对于翻修植入物而言,这是一个更大的挑战,因为手术期间通常需要同种异体移植物来获得植入物的即时稳定性。骨移植会迅速被吸收。因此,在新骨形成充分建立并能机械固定假体之前,假体可能会出现不稳定。锶是一种具有双重作用的药物,兼具促骨合成和抗骨分解作用。以雷奈酸锶的形式,它被用于治疗骨质疏松症。锶可能会改善植入物的早期骨整合和固定。本论文由三项研究组成,调查锶在骨 - 植入物界面的作用。问题一是,将锶输送到界面的最佳方法是什么;问题二是,锶能否在界面发挥其双重作用。这些研究在犬类非骨水泥实验性间隙模型中进行。通过对骨整合的组织形态计量学分析和植入物固定的机械推出试验来评估锶的作用。每项研究的组织形态计量学分析使用了不同的体视学方法。所使用的方法经过严格审查,结果有效。研究I在观察4周和12周后,将5%锶取代的羟基磷灰石(HA)涂层与HA涂层进行比较。我们研究了锶取代是否能改善植入物的固定。发现在这两个时间点中的任何一个,锶取代的HA涂层都没有改善植入物的固定。研究II将5%锶掺杂的HA骨移植填充剂与HA骨移植填充剂进行比较。骨移植填充剂与同种异体移植物混合,并围绕钛植入物进行打压。本研究的目的是确定骨移植填充剂的锶掺杂是否能保护同种异体移植物不被快速吸收,并增加间隙愈合,从而改善植入物的固定。我们发现锶掺杂增加了间隙愈合并保护了同种异体移植物,然而,机械测试结果尚无定论。原因可能是在4周的观察期内,增加的间隙愈合尚未到达植入物,所以植入物上的生长没有得到改善。研究III调查了含0%、10%或50%锶取代的生物活性玻璃涂层与喷砂钛合金植入物的HA涂层相比的效果。目标是确定生物活性玻璃涂层是否能改善植入物的固定,然后涂层的锶取代是否能以剂量依赖的方式进一步改善。不幸的是,生物活性玻璃涂层失败了,可能是由于喷砂粉末中的铝污染。HA涂层植入物在骨整合和植入物机械固定的所有参数方面都更优。这些研究表明进行进一步实验研究的重要性。即使是研究一种已知药物在新应用中的情况。作为HA骨移植填充剂掺杂形式的锶在界面显示出作为双重作用剂的潜力。然而,将锶输送到骨 - 植入物界面的方法显然需要进一步研究。

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