We have proposed a hypothesis that generalised OA is a metabolic disorder in which systemic factors induce changes in skeletal tissues by modifying the formation and biosynthetic activity of cells derived from mesenchymal precursors (8). In this case, the erosion of articular cartilage would be mechanically driven, but the disease itself would not. However, this is only a small part of the disease process. This hypothesis can also offer explanations for the changes in bone, even at sites remote from joints (9;10), in other tissues such as muscle (11;12), and for the link with obesity. What is becoming clear, however, is that searching for changes among the articular cartilage matrix proteins is not likely to yield significant insight into the disorder except in rare cases.

Osteoarthritic changes in juxta-articular bone are well described with sclerosis of the subchondral bone, the formation of so-called ‘cysts’ within it, and the development of osteophytes. This involvement of the bone is universally recognised, though it is largely believed to be a secondary consequence of the disease. More recently, alterations have been found in the bone matrix and in osteoblast behaviour which are difficult to explain as secondary changes. There is a reduced mineralisation in the femoral head (13-15), increased formation of woven bone and evidence for enhanced osteoclastic activity (16). Patients with OA changes evident on hip radiographs were found to have a higher than average bone mineral density not only in the hip but also in the distal radius, vertebrae and calcaneus (17). Increased mineralisation and greater levels of growth factors were found in the iliac crest of patients with OA of the hand (9). These matrix changes are reflected in cellular changes and it has been shown that osteoblasts from patients with OA proliferate in vitro more rapidly than normal and express different levels of markers (18;19).

Fig 1 Total serum cholesterol and body mass index in a random selection of patients presenting for a total hip replacement in Aberdeen with the WHO definitions of overweight and obese and the Scottish Intercollegiate Guidelines Network threshold for intervention for hyperlipideamia. An indication of the expected normal range is shown shaded.

Fig 2 Total lipid content in cancellous bone (including marrow) of the hip expressed as mass per unit volume of bone tissue. Despite the increased porosity of osteoporotic bone it contains only half the fat content of bone from patients with OA.

Fig 3. Fatty acid contents of lipids extracted from the OA and OP bones showed different profiles in the two diseases. Of particular note is the two-fold higher level of arachidonic acid in OA, in the light of its role as a precursor for the pro-inflammatory PGE2. (*P<0.05, **P<0.01, ***P<0.001)

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