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关节内注射皮质类固醇对韧带特性的影响:恒河猴膝关节的生物力学和组织学研究

Effect of intra-articular corticosteroids on ligament properties: a biomechanical and histological study in rhesus knees.

作者信息

Noyes F R, Grood E S, Nussbaum N S, Cooper S M

出版信息

Clin Orthop Relat Res. 1977 Mar-Apr(123):197-209.

PMID:404109
Abstract

The effect of intra-articular corticosteroid injections (methylprednisolone acetate) on the mechanical properties of anterior cruciate bone-ligament-bone units was determined. Fifty-one wild rhesus animals provided 88 knee ligaments units that were loaded in tension to failure under fast strain-rate conditions. Alterations in ligament strength and load-elongation properties were found to depend upon corticosteroid dosage and time after injection. Fifteen weeks after the higher drug dosage (methylprednisolone acetate, 6 mg/kg; three injections, spaced weekly) significant decreases occurred in the maximum failure load (20%), energy absorption prior to failure (11%) and linear stiffness (11%) of the ligament unit. In contrast, only minimal non-significant alterations in ligament strength properties occurred at the higher drug usage after 6 weeks in a second group of animals. this strong time-dependence may partially explain the negative findings reported in short term studies. The higher drug dosage used is approximately 10 times an equivalent human dose on a body mass basis and indicates the ability of this class of drugs to significantly alter the mechanical properties of a ligament unity. A third group of animals received a total of two intra-articular coticosteroid injections (single injections spaced two weeks apart) at a dosage (0.6 mg/kg) equivalent to that commonly used clinically in humans. Statistically significant decreases occurred in maximum failure load (9%) and energy absorption (8%); however, this change is believed of little importance to the projected functional capacity of the ligament unit. No detectable systemic effect of the intra-articular corticosteroid injections was found on the mechanical properties of the ligament unit in the extremity opposite to that which received the drug injection. Histological examination after failure showed normal cellularity and staining characteristics of the ligament, fibrocartilage junction and underlying bone. No bone resorptive changes were observed beneath the ligament insertion site. Failure by a ligamentous mode remained the most common mechanism of specimen failure. Scanning Electron Microscopy showed failure of collagen fibers at multiple levels throughout the ligament indicative of a serial pull-apart failure process. A rich supply of vessels to the anterior cruciate ligament was demonstrated and failure of the vessels occured by a necking down process. Insofar as the results apply to humans, they infer the potential for high and frequent doses of intra-articular slightly soluble corticosteroids to produce alterations in ligament strength and function. A single intra-articular injection or one repeated at intervals of several months probably carries little risk to ligament properties.

摘要

研究了关节内注射皮质类固醇(醋酸甲泼尼龙)对前交叉韧带-骨单元力学性能的影响。51只野生恒河猴提供了88个膝关节韧带单元,在快速应变率条件下对其进行拉伸加载直至破坏。发现韧带强度和负荷-伸长特性的改变取决于皮质类固醇的剂量和注射后的时间。高剂量药物(醋酸甲泼尼龙,6mg/kg;每周注射一次,共三次)注射15周后,韧带单元的最大破坏负荷(降低20%)、破坏前的能量吸收(降低11%)和线性刚度(降低11%)均出现显著下降。相比之下,在第二组动物中,高剂量药物使用6周后,韧带强度特性仅出现极小的、无统计学意义的改变。这种强烈的时间依赖性可能部分解释了短期研究中报道的负面结果。按体重计算,所使用的高剂量药物约为人类等效剂量的10倍,表明这类药物有能力显著改变韧带单元的力学性能。第三组动物接受了总共两次关节内皮质类固醇注射(单次注射,间隔两周),剂量(0.6mg/kg)与临床上常用于人类的剂量相当。最大破坏负荷(降低9%)和能量吸收(降低8%)出现了统计学上的显著下降;然而,这种变化被认为对韧带单元的预计功能能力影响不大。未发现关节内注射皮质类固醇对接受药物注射肢体对侧的韧带单元力学性能有可检测到的全身影响。破坏后组织学检查显示韧带、纤维软骨交界处和下方骨的细胞数量和染色特征正常。在韧带插入部位下方未观察到骨吸收变化。韧带模式破坏仍然是标本破坏最常见的机制。扫描电子显微镜显示整个韧带多处胶原纤维破坏,表明存在连续的撕开破坏过程。证实前交叉韧带血管丰富,血管破坏是通过变细过程发生的。就结果适用于人类而言,提示高剂量和频繁关节内注射微溶性皮质类固醇有改变韧带强度和功能的可能性。单次关节内注射或每隔几个月重复注射一次可能对韧带性能几乎没有风险。

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