Osteoarthritis is a disease of synovial joints characterized by cartilage loss with an accompanying periarticular bone response. There is no simple definition of OA as it requires consideration of three overlapping areas – pathological changes, radiological features and clinical consequences. Pathologically, there is an alteration in cartilage structure, radiologically there are osteophytes and joint space narrowing, and clinically some patients complain of pain and disability.

Epidemiology

Osteoarthritis is the most common type of arthritis. The prevalence increases with age, and most people over 60 years will have some radiological evidence of it. It occurs world-wide, although OA of the hip is less common in black Africans and Chinese populations than in Caucasians. Most epidemiological studies have been based on radiological evidence, which is much more frequent than symptomatic OA. Women over 55 years are affected more commonly than are men of a similar age. There is a familial pattern of inheritance with distal interphalangeal joint involvement as the hallmark (nodal OA) and also with primary generalized OA. OA has a variable distribution. The resulting disabilities have major socio-economic resource implications, particularly in the developed world.

Aetiology

Genes that encode collagen type II have been proposed as candidate genes for familial OA. Osteoarthritis is the result of active, sometimes inflammatory but potentially reparative processes rather than the inevitable result of trauma and ageing. Focal destruction of the articular cartilage is the common pathological feature. The spectrum of OA ranges from atrophic disease in which cartilage destruction occurs without any subchondral bone response, to hypertrophic disease in which there is massive new bone formation at the joint margins.

Cartilage is a matrix of collagen fibres (mainly type II), enclosing a mixture of proteoglycans and water. Proteoglycans are present mainly as large molecular aggrecans, which consist of a protein core with attached chondroitin sulphate and keratan sulphate chains. The gene for human aggrecan has been cloned, and polymorphisms of the gene have been correlated with OA of the hand in older men.

Cartilage is smooth-surfaced and shock-absorbing. Under normal circumstances there is a dynamic balance between cartilage degradation by wear and its production by chondrocytes. Early in the development of OA this balance is lost and, despite increased synthesis of extracellular matrix, the cartilage becomes oedematous. Focal erosion of cartilage develops. Chondrocytes die and, although repair is attempted from adjacent cartilage, the process is disordered. Eventually the synthesis of extracellular matrix fails and the surface becomes fibrillated and fissured. Cartilage ulceration exposes underlying bone to increased stress, producing microfractures and cysts. The bone attempts repair but produces abnormal sclerotic subchondral bone and overgrowths at the joint margins, called osteophytes. There is some secondary inflammation.

These occur in 75% of patients with advanced breast and prostate cancer and in 25% of patients with other solid tumours, e.g. lung, GI tract, thyroid, bladder or kidney.

Metastases are either osteolytic or osteoblastic with some patients having both.

Prostate cancer is predominantly osteoblastic while most patients with breast cancer have osteolytic lesions.
In multiple myeloma the lesions are purely osteolytic.

Bone is a frequent site of metastases due to:

• high blood flow
• tumour cell production of adhesins which bind them to marrow stromal cells
• growth factors in bone, including TGFβ, insulin-like growth factor (ILG)-1 and 2, platelet-derived growth factor and fibroblastic growth factors.

Osteolytic metastases

The destruction of bone is mediated by osteoclasts and not the tumour cells. Tumour cells produce parathyroid hormone-related peptide, IL-6, prostaglandin E2, TNF and macrophage colony-stimulating factor (M-CSF) which increase the expression of receptor activity of nuclear factor κB ligand (RANKL) which directly induces formation of osteoclasts and bone resorption. Bone destruction increases calcium levels, which promotes both tumour growth and the production of PTH-related peptide, which is a major factor in osteolytic bone destruction in many tumours. In multiple myeloma there is, additionally, inhibition of osteoblast activity.

Osteoblastic metastases.

The mechanism for this is less clear. It has been suggested that osteoclastic activity precedes osteoblastic activity and bone formation. It is also possible that the vicious circle (as in osteoclastic activity) may be in action, whereby the tumour induces osteoblastic activity and the release of growth factors for osteoblasts, which then increases the growth of tumours. Endothelin 1 has been shown to stimulate bone formation and its levels are increased in, for example, prostate and breast cancers.