Heberden Oration, 1976. Molecular approach to the understanding of osteoarthrosis.

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Abstract
The experimentally induced osteoarthrosis [in dogs] reproduced the changes in the joint and the biochemical changes in the cartilage that were seen in naturally occurring canine osteoarthrosis. These change were similar to those observed in human osteoarthrosis. The experimental model enables the early events to be studied so that a chronological sequence may be established. Changes occur first in the areas where lesions will later develop, they then spread to areas immediately surrounding lesions and finally the entire cartilage of the joint is involved even where lesions do not develop. In its initial stages osteoarthrosis appears to involve profound changes in the metabolism of cartilage cells set in train by increased hydration of the tissue; only at advanced stages does it become degenerative. At what stage the metabolic changes are reversible is a question of crucial importance in understanding the disease process and in attempting to develop effective therapeutic measures.