Chondrocalcinosis, osteophytes and osteoarthritis.

An association between osteoarthritis (OA) and radiographic evidence of chon-drocalcinosis (CC) has been recognised for years. Crystals of calcium pyrophos-phate 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, Wil-son'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 osteo-phyte 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 phago-cytosis 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 metallopro-teinases, 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 pro-teoglycan loss from the cartilage matrix, suggesting that crystals present in syno-vial fluid may cause increased wear of the articular surface in vivo. 4 Furthermore , calcium crystals are phlogistic; their presence within the joint space and synovium may initiate an inflammatory response. 5 Radiography of OA The paper by Neame et al in this issue of the Annals examines the association between knee OA and CC from an epidemiological perspective. 6 Subjects in this cross sectional study were defined as having OA on the basis of radiographic evidence of a definite osteophyte and definite joint space narrowing (JSN, a surrogate for thinning of the articular cartilage). …