The effect of systemic corticosteroids on rabbit articular cartilage

Abstract

Rabbits were treated for up to 9 weeks with daily doses of cortisone. Cartilage from the distal femur was studied biochemically at regular intervals, and no change in the content of DNA but a significant and progressive decline in the concentration of hexosamine were noted. In vitro incorporation of J5S04 and W-glycine was depressed markedly. Because the test animals lost 25% of their body weight, a separate group of starved controls were studied and the changes noted were similar to those seen with corticoid treatment but were not as marked.Prior studies from this and other laboratories demonstrated the potential deleterious effects of intraarticularly administered corticosteroids on articular cartilage of experimental animals. It has been shown that, when injected into the animal joint, both soluble and slightly soluble steroid products used in clinical treatment may significantly inhibit protein and polysaccharide synthesis by the chondrocyte, and that prolonged treatment may produce specific pathologic lesions (1 -5). Submitted for publication April 19, 1972; accepted July 13, 1972. Numerous reports have indicated that systemically administered corticosteroids may alter cell metabolism and, specifically, can cause inhibition of protein and polysaccharide synthesis in a number of organs (5-19). Little is known, however, regarding the effect of the hormone(s) on articular cartilage; but, from the data reported for other tissues, as well as theoretic considerations, it would seem likely that systemically administered steroids would significantly interfere with the anabolic activities of the cartilage cell.The purpose of this report is to describe the results of an experimental study in which cortisone acetate, 4.5 mg/kg/day, was administered intramuscularly to adult rabbits. T h e articular cartilage from the distal femur was analyzed for alterations in biochemical constituents and rates of synthesis of the matrix at intervals up to 9 weeks. Early analyses of the data demonstrated a significant effect on the general metabolic state of the rabbit, as indicated by a weight loss of up to 28.8%. These findings dictated a second metabolic experiment, in which another group of rabbits was partially starved over a 7-week period. T h e articular cartilage from both groups of animals was studied biochemically and metabolically, and the data showed a significant depletion in polysaccharide content and a decrease in rates of synthesis of both protein and polysaccharide of the matrix, more severe in the steroid-treated group than in the starved controls. T h e changes were proportional to the duration of the study and the severity of the systemic catabolic state, as measured by weight loss. O n the basis of these observations, it is possible to speculate on the effect of systemically administered corticosteroids on rabbit articular cartilage and the relationship of this response to starvation and negative nutritional balance. MATERIALS AND METHODSAdult New Zealand white (NZW) rabbits were obtained Study 1Forty N Z W r...

Effect of intra-articular corticosteroid injections on primate cartilage.

“…Decrease in the size of chondrocytes and cell death were observed by Silberberg et al (1966) in the articular cartilage of mice given systemic cortisone. Layton (1951) 0-9 mol/Il MgCl, reported that cortisone inhibited the synthesis of chondroitin sulphate by chick embryo and wound tissues in vitro, and Mankin et al (1972) observed marked reduction of in vitro glycosaminoglycan synthesis by cartilage removed from cortisonetreated rabbits.…”

Musculoskeletal System

“…Corticosteroids are quite frequently employed by this route to reduce synovial inflammation accompanying osteoarthritis, rheumatoid or other forms of arthritis. 151,185,186 Injection of rabbit knee joints with triamcinolone acetonide, a potent fluorinated corticosteroid for periods of up to six weeks, produced degeneration of chondrocytes in tangential and transitional zones of articular cartilage. 183 However, degenerative changes in articular cartilage and underlying bone have also been ascribed to intra-articular injection of corticosteroids in patients, although the pathogenesis for the alterations is not clear.…”

Physiological levels of hydrocortisone maintain an optimal chondrocyte extracellular matrix metabolism

“…Most early in vivo experiments showed that corticosteroids, especially after intra-articular administration, may provoke or worsen cartilage lesions. [1][2][3][4][5][6][7][8][9] However, a systematic review of these reports shows that degeneration of articular cartilage, resulting from steroid administration, occurred after the administration of unrealistically high doses of this hormone. Similarly, Charcot-like arthropathy has been reported in man after a series of about 20 intra-articular injections of steroids.…”