Degradative changes in human articular cartilage induced by chemotherapeutic agents.

We determined the effects of cytotoxic drugs on human articular cartilage by studying patients who received cancer chemotherapy. Tissue morphology and the biochemical findings of the "treated" cartilage were compared with those of "normal" human cartilage. The histological and ultrastructural studies showed that degeneration and repair occurred simultaneously. Degenerative changes included: chondrocytic alterations, collagen network disruption, decreased safranin-O staining at the superficial layer and pericellular area of the midlayer chondrocytes. Repair was shown by cartilage hypercellularity and clone formation. Some chondrocytes showed intense perilacunar metachromasia. Abnormal biochemistry included increased amounts of DNA content; total neutral collagenolytic enzyme and metalloproteoglycan-degrading enzyme (NMPE) activities; and the active form of the neutral collagenolytic enzyme. The cartilage proteoglycan content was lower in treated patients than in controls. Thus, chemotherapeutic agents can induce cartilage changes similar to those of early osteoarthritis. The reversibility of these changes and drug effects on diseased cartilage remain to be determined.