Millett Peter J, Allen Matthew J, Bostrom Mathias P G
The Hospital for Special Surgery, New York, NY 10021, USA.
J Bone Joint Surg Am. 2002 Feb;84(2):236-49. doi: 10.2106/00004623-200202000-00011.
Particle-induced osteolysis is currently a major problem affecting the long-term survivorship of total joint replacements. Alendronate is a third-generation bisphosphonate that blocks osteoclastic bone resorption. The objective of this study was to determine whether alendronate could prevent particle-induced osteolysis or restore (reverse) bone loss in established osteolysis.
A rat model of particle-induced osteolysis was used. A specially designed polyethylene implant was placed in the proximal part of the right tibia of seventy-two animals. Following four weeks of healing, the animals were randomized into control groups, a prevention group, or a treatment group. In the prevention group, animals received intra-articular injections of high-density polyethylene particles (mean size, 2 m; all <10 m) at four, six, and eight weeks postoperatively. Alendronate (0.01 mg/kg/day) was administered concomitantly through an implantable pump from the fourth week through the tenth week. In the treatment group, animals were also exposed to polyethylene particles at four, six, and eight weeks, to establish bone loss, but they received alendronate subsequently, from the tenth week through the sixteenth week, to treat the bone loss. Positive (particle-only) and negative (saline-solution-only) control groups were assessed as well. Tissues were harvested at ten weeks in the prevention group and at sixteen weeks in the treatment group. Histological analyses and histomorphometric determinations of the periprosthetic bone volume were carried out.
Histological examination showed a rim of new bone (neocortex) around the implant in the untreated and saline-solution-treated control animals (no polyethylene particles). Treatment with saline solution (no polyethylene particles) did not affect periprosthetic bone. Animals exposed to polyethylene particles had bone loss. In those that received alendronate, the bone loss was either prevented or reversed, and the quantity of neocortical and trabecular bone was increased compared with that of the controls. Alendronate effectively preserved periprosthetic bone in both the prevention and treatment groups. In the prevention arm, the mean periprosthetic bone volume of the neocortex and the surrounding trabecular bone, as determined with histomorphometry, was 21.5% +/- 6.5% in the saline-solution-treated controls (no particles), 13.1% +/- 5.9% in the particle-treated animals, and 32.6% +/- 6.4% in the alendronate-treated animals (p < 0.001). In the treatment arm, the mean periprosthetic bone volume was 27.2% +/- 5.6% in the saline-solution-treated controls, 17.7% +/- 6.2% in the particle-treated animals, and 30.2% +/- 5.9% in the alendronate-treated animals (p = 0.002).
In our model, the intra-articular injection of polyethylene particles caused substantial bone loss around a loaded implant. Alendronate effectively prevented and treated the particle-induced periprosthetic bone loss.
颗粒诱导的骨溶解是目前影响全关节置换长期存活率的一个主要问题。阿仑膦酸钠是一种第三代双膦酸盐，可阻断破骨细胞的骨吸收。本研究的目的是确定阿仑膦酸钠是否可以预防颗粒诱导的骨溶解或恢复（逆转）已发生骨溶解中的骨质流失。
采用颗粒诱导的骨溶解大鼠模型。将一个特殊设计的聚乙烯植入物置于72只动物右胫骨近端。愈合4周后，将动物随机分为对照组、预防组或治疗组。在预防组中，动物在术后4周、6周和8周接受关节内注射高密度聚乙烯颗粒（平均大小为2μm；均<10μm）。从第4周开始至第10周，通过植入式泵同时给予阿仑膦酸钠（0.01mg/kg/天）。在治疗组中，动物同样在4周、6周和8周接触聚乙烯颗粒以造成骨质流失，但随后从第10周开始至第16周接受阿仑膦酸钠治疗骨质流失。还评估了阳性（仅颗粒）和阴性（仅生理盐水溶液）对照组。预防组在10周时、治疗组在16周时采集组织。对假体周围骨体积进行组织学分析和组织形态计量学测定。
组织学检查显示，在未处理和用生理盐水处理的对照动物（无聚乙烯颗粒）中，植入物周围有一层新骨（新皮质）。用生理盐水处理（无聚乙烯颗粒）不影响假体周围骨。接触聚乙烯颗粒的动物出现骨质流失。在接受阿仑膦酸钠治疗的动物中，骨质流失得到预防或逆转，与对照组相比，新皮质和小梁骨的量增加。阿仑膦酸钠在预防组和治疗组中均有效保留了假体周围骨。在预防组中，通过组织形态计量学测定，生理盐水处理的对照组（无颗粒）假体周围新皮质和周围小梁骨的平均骨体积为21.5%±6.5%，颗粒处理的动物为13.1%±5.9%，阿仑膦酸钠处理的动物为32.6%±6.4%（p<0.001）。在治疗组中，生理盐水处理的对照组假体周围平均骨体积为27.2%±5.6%，颗粒处理的动物为17.7%±6.2%，阿仑膦酸钠处理的动物为30.2%±5.9%（p=0.002）。
在我们的模型中，关节内注射聚乙烯颗粒导致负重植入物周围大量骨质流失。阿仑膦酸钠有效预防和治疗了颗粒诱导的假体周围骨质流失。
Zotero 插件