Association between OA and chondrocalcinosis

An association between osteoarthritis (OA) and radiographic evidence of chondrocalcinosis (CC) has been recognised for years. Crystals of calcium pyrophosphate dihydrate (CPPD) may be found in synovial fluid from patients with OA who are relatively asymptomatic as well as from those who are experiencing an acute flare up of joint pain due to an attack of pseudogout. Whether CC is the cause of OA in such people or develops as a result of changes in metabolism of the chondrocyte or in the extracellular matrix of the articular cartilage is unclear. In any event, conditions associated with CC, such as hyperparathyroidism, Wilson’s disease, and haemochromatosis, are well recognised causes of “secondary” OA.¹

Chondrocytes from patients with OA who do not exhibit CC produce as much pyrophosphate as those from the cartilage of patients with CPPD disease.² Furthermore, chondrocytes from human OA cartilage exhibit increased sensitivity to transforming growth factor β (TGFβ), which has been shown to induce osteophyte formation in murine knee joints, an effect not seen with insulin-like growth factor 1.³ TGFβ also stimulates the secretion of pyrophosphate by chondrocytes, predisposing to formation of pericellular CPPD crystals; the phagocytosis of which results in the synthesis of matrix metalloproteinases by chondrocytes.⁴ These enzymes participate directly in the breakdown of the extracellular matrix of the cartilage and activate latent proenzymes and growth factors that cause further structural damage. Calcium crystals also decrease the synthesis of proteinase inhibitors, such as tissue inhibitors of metalloproteinases, exacerbating tissue damage.⁴

In addition to the effects of CPPD crystals on cartilage cited above, calcium crystals may produce direct mechanical damage to articular cartilage. Addition of CPPD crystals to the solution bathing cartilage plugs that were subjected to mechanical wear in vitro increased proteoglycan loss from the cartilage matrix, …