Kalbhen D A
Institute of Pharmacology and Toxicology, University of Bonn, FRG.
Scand J Rheumatol Suppl. 1988;77:13-22. doi: 10.3109/03009748809096930.
A large number of experimental data have given evidence that many NSAIDs can inhibit the synthetic processes of connective tissue in-vitro and ex-vivo. During the past 18 years we have investigated the in-vivo effect of antirheumatic drugs on knee joint cartilage using rats and hens. Single or once-weekly intraarticular injections of salicylates, indomethacin, phenylbutazone, naproxen, ibuprofen, clofezone, fufenamic acid, niflumic acid, or dexamethasone induced morphological alterations in the joint cartilage and subchondral bone, which were demonstrable by means of histology, stereoelectron-microscopy, biochemistry and X-ray. The cartilage of these laboratory animals had a faster turnover compared to man, and the degenerative and destructive processes occurred within 8-12 weeks and were identical or very similar to osteoarthritis in man. In contrast to the general opinion that all NSAIDs possess more or less the same pharmacological properties, the influence of these drugs on articular cartilage was, surprisingly, quite different. In our animal experiments we found that comparable doses between NSAIDs, such as fenbufen, ketoprofen, diclofenac, and tiaprofenic acid, did not induce any degenerative processes in cartilage and subchondral bone in-vivo. A documentation of our radiographical, macroscopical and histomorphological results demonstrated the pronounced differences between NSAIDs on joint tissue. Our experimental data suggested that in the pharmacotherapy of osteoarthritis a specific selection of NSAIDs between those with catabolic and those with non-catabolic characteristics in regard to connective tissue metabolism was important and beneficial.
大量实验数据表明，许多非甾体抗炎药在体内外均可抑制结缔组织的合成过程。在过去18年中，我们使用大鼠和母鸡研究了抗风湿药物对膝关节软骨的体内作用。单次或每周一次关节内注射水杨酸盐、吲哚美辛、保泰松、萘普生、布洛芬、氯苯宗、氟芬那酸、尼氟酸或地塞米松可导致关节软骨和软骨下骨出现形态学改变，这些改变可通过组织学、立体电子显微镜、生物化学和X射线检测到。与人类相比，这些实验动物的软骨周转更快，退变和破坏过程在8 - 12周内发生，且与人类骨关节炎相同或非常相似。与普遍认为所有非甾体抗炎药或多或少具有相同药理特性的观点相反，令人惊讶的是，这些药物对关节软骨的影响差异很大。在我们的动物实验中，我们发现非甾体抗炎药如芬布芬、酮洛芬、双氯芬酸和噻洛芬酸之间的等效剂量在体内并未诱导软骨和软骨下骨出现任何退变过程。我们的影像学、大体和组织形态学结果记录表明了非甾体抗炎药对关节组织的显著差异。我们的实验数据表明，在骨关节炎的药物治疗中，根据结缔组织代谢情况，在具有分解代谢和非分解代谢特征的非甾体抗炎药之间进行特定选择是重要且有益的。
