Animal Studies
It is well known and accepted that medications must first be shown to be safe in animals before they are given or injected into human beings. It is also much easier to study the effects of the drugs, or injection of the drugs, in animals because the animals can be sacrificed, and the tissues examined under a microscope. This allows the researcher to evaluate not only the potential beneficial effect of the medication, but also detrimental effects.
 Using tritiated glycine (glycine 3H) as an indicator of amino acid incorporation in protein synthesis in cartilage matrices, Mankin and Conger injected hydrocortisone acetate into rabbit knees. Their data showed a rapid and profound decrease in glycine incorporation that appeared to depend on dosages. Maximum decline was seen six hours after the injection.28 They did a similar experiment using glycine 14C as the radiotracer, which showed a definite decrease in the rate of protein synthesis within two hours of the injection. They noted that the rate of the inhibitory effect of intraarticular hydrocortisone on cartilage protein synthesis was about twice that of the observed rate for corticosteroids given by intramuscular route.29 One year later, researchers injected hydrocortisone into normal rabbit knees and produced thinning of the cartilage, and the development of fissures and fibrillations in the articular cartilage. They also found multiple small white deposits within the substance of the articular cartilage, which were found to represent cystic areas of degeneration within the middle zone of the cartilage matrix. These effects were most marked in the animals which had the greatest number of injections.30 Deleterious effects of cortisone were reported by some researchers who noted that the drug inhibited the synthesis and deposition of chondroitin sulfate in cartilage.31-33 Many research papers have documented that corticosteroids reduced radiosulfate uptake into chondroitin sulfate, thereby decreasing cartilage growth and repair.34-37 Other research on the articular cartilage of rabbits showed that the destruction of articular cartilage by corticosteroids worsened with time. Microscopic degenerative changes were progressively more evident, including loss of protein polysaccharide in the matrix, decreased number of chondrocytes, loss of cell shape, distortion of the cell membrane and nucleus leading to chondrocyte degeneration, multiple fissuring of the matrix, clumping of collagen, and finally by the sixth month, appearance of large cysts containing debris and degenerated chondrocytes.38-41 (See Figure 6.)
 In regard to the progression of OA, is the articular cartilage damage seen from the disease or from the steroid injection treatments? One research paper put it this way: After administration of corticosteroids to patients suffering from arthritis, it is impossible to decide how much damage is due to the steroids and how much is due to the natural progress of the disease. To answer this question, these researchers devised a study to look at what happens to rabbit articular cartilage subjected to corticosteroid concentrations compatible with what we observed in human patients. They compared this group to normal control animals who received no injections. They also induced an artificial arthritis in one group of animals, used them as another control, and saw what happened to some of these animals if they also were subjected to low dose corticosteroids. Compared to the control groups, the corticosteroids caused severe deleterious effects on the articular cartilage. The articular cartilage became thin, the matrix near the surface lost its hyaline appearance and became fibrous, the surface fibrillated, and the arthritic cartilage lost its ability to repair itself. This last effect caused the researchers to state It must be expected that corticosteroids can retard or prevent recovery in naturally occurring joint diseases. Administration of these drugs must therefore be considered with caution.42 This last quote was written in 1973. For this review I purposely used old research to emphasize the point that the effects of corticosteroids have been known for years. Current research done in 2007 on rabbit cartilage continues to confirm that corticosteroid injections into the knee joints of rabbits causes cartilage necrosis.43
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