Epidemiology

OA is the commonest type of arthritis. Radiographic and autopsy surveys show a steady age-related increase in prevalence from the age of 30 years. By the age of 65 years, 80% of people have some radiographic evidence of OA, although only one in four is symptomatic. The joints most frequently affected are the spine, hips, knees, and some of the small joints of the hands and feet (Fig. 15.1). Community-based studies in the UK have shown that 10% of the population over the age of 55 years have troublesome knee pain and, of those, 25% are severely disabled. OA is the leading cause of physical disability in people age over 65 years. The prevalence of both radiographically defined OA and OA-related disability is greater in women than in men. Although disability associated with OA also increases steadily with age, the majority of people with OA-related disability in the community are between the ages of 55 and 75 years.

FIGURE 15.1 Hand osteoarthritis

Risk factors for OA include constitutional factors such as age, sex, the shape and alignment of joints, obesity and some genetic determinants, but there are also important environmental triggers, such as previous injury or the repetitive trauma associated with certain recreational activities, such as weightlifting or long-distance running, and with some occupations, such as mining and farming. Mechanical factors play a role in the pathogenesis of all types of primary, as well as secondary, OA. Joint failure occurs when mechanical stresses overwhelm the capacity of articular tissues to resist and repair the damage. Structural failure of the articular cartilage, bone and periarticular tissues can result from abnormal mechanical stresses damaging previously normal tissues, or from the failure of pathologically impaired joint tissues in response to physiologically normal mechanical forces (Fig. 15.2). Obesity, joint mal-alignment, occupational trauma and muscle weakness are all important, potentially modifiable, biomechanical risk factors that determine the site and severity of the disease. Race and ethnicity have some influence on the probability of developing OA at different sites. Although OA of the knee is prevalent in all ethnic groups (particularly frequent in black women), hip, hand and generalized OA are seen predominantly in Caucasians. Genetic factors are known to be important determinants. Twin studies suggest heritability of up to 65% in primary OA of the hand and knee, but the susceptibility genes themselves still remain largely undefined.

FIGURE 15.2 Factors leading to osteoarthritis

Progress has been made in identifying mutations in collagen genes that are associated with different types of bone and cartilage dysplasia where OA is part of a more complex phenotype, but none of these single gene mutations in genes that code for structural matrix proteins appears to be important in determining susceptibility to the common types of OA. Recently, however, there has been some progress in identifying a promoter polymorphism in a bone morphogenetic protein (growth differentiation factor 5) that is associated with both hip and knee OA, as well as other polymorphisms in genes that code for signalling proteins involved in the development and maintenance of articular cartilage, which appear to be associated with susceptibility to hip OA in certain ethnic groups (see Chapter 3).

Pathology and pathogenesis

OA involves all tissues of the joint (subchondral bone, ligaments, capsule and synovial membrane) as well as the articular cartilage, but inflammatory changes in the synovium are usually minor and secondary. To a variable extent OA is a dynamic process characterized by remodelling of the anatomy of the joint and proliferation of new bone in the form of osteophytes, as well as by focal degeneration of articular cartilage. In many cases these processes reach a state of non-progressive equilibrium, but in others there is symptomatic failure of the joint characterized by progressive degeneration of the articular cartilage with fibrillation, fissuring, ulceration and, eventually, full-thickness focal loss of cartilage at sites of joint loading. In addition, with wear, there is compaction and sclerosis (‘eburnation’) of the adjacent subchondral bone and the formation of bone cysts (Fig. 15.3). The biomechanical properties of the cortical and subchondral bone play an important role in protecting articular cartilage following impact loading. It is suggested that the pathogenesis of OA in some cases may be initiated by an increase in the density and stiffness of the subchondral bone following the healing of microfractures caused by unprotected loading of joints. The consequent loss of bone viscoelasticity results in steep stiffness gradients in the bone. This in turn results in stretching and fibrillation of the overlying articular cartilage, as well as focal osteonecrosis and the formation of bone cysts. In support of this hypothesis, patients with hip and knee OA have higher than normal bone mass and there is evidence that focal increases in subchondral bone density can precede and predict future cartilage loss in patients with OA of the knee. The sequence of pathological and biochemical changes in the articular cartilage in OA follows a characteristic pattern (Table 15.2), whether primary or secondary to changes in the subchondral bone. Early increases in matrix hydration and articular cartilage thickness follow disruption of the collagen fibre network, loss of tensile strength in the superficial zone of the articular cartilage and swelling of the negatively charged, high-molecular-weight proteoglycan, aggrecan. Initially, chondrocyte activation and proliferation of clusters of chondrocytes are associated with an anabolic response with increased synthesis and turnover of matrix collagens and proteoglycans, but in the later stages of OA, catabolism of cartilage matrix proteins outstrips the capacity for cartilage repair. Anabolic mediators include growth factors, such as the insulin-like growth factor (IGF-1), fibroblast growth factor (FGF), transforming growth factor β (TGFβ) and the bone morphogenetic proteins (BMPs): the anti-inflammatory cytokine interleukin (IL)-4 and proteinase inhibitors, such as tissue inhibitors of metalloproteinases (TIMPs) and plasminogen activator inhibitor (PAI). Catabolic mediators include nitric oxide, prostaglandins and the pro-inflammatory cytokines IL-1β, tumour necrosis factor (TNFα), IL-6 and IL-17, as well as metalloproteinases (MMP-1, -8, and -13) and aggrecanases (ADAM-TS-4 and -5).

FIGURE 15.3 Radiographic appearances of osteoarthritis, showing loss of joint space and sclerosis in both hands, especially at the first carpometacarpal joint

Table 15.2 Structural, cellular and biochemical changes in articular cartilage in osteoarthritis

Clinical features

Pain is the presenting symptom in the majority of patients. Usually insidious in onset and intermittent at first, the pain is typically aching in character. Initially, it is provoked by weight-bearing or movement of the joint, and relieved by rest, but as the disease progresses the pain may be more prolonged and experienced at rest, and may become severe enough to wake the patient at night. Prolonged early morning stiffness is not a feature as it is in rheumatoid arthritis and other predominantly inflammatory joint diseases, but a few minutes of early morning stiffness and transient stiffness (gelling) after rest are common. Pain in OA can emanate from all the tissues of the joint, except the articular cartilage, which is aneural. Pain may result from increased pressure or microfractures in the subchondral bone, from low-grade synovitis, inflammatory effusions, capsular distension, enthesitis or muscle spasm, and nocturnal aching may be associated with hyperaemia in the subchondral bone. Associated anxiety and depression are not uncommon, and these can amplify pain and disability. There is only a weak relationship between symptoms and radiographic evidence of structural changes of OA at all joint sites, although the correlation between pain and structural changes is somewhat stronger in the weight-bearing joints (hip > knee) than in the small joints of the hands. Patients may develop painless functional impairment due to restricted movement in the hands, hips or knees. Physical signs associated with OA include: restriction of movement of joints as a result of capsular fibrosis or blocking by osteophytes, palpable bony swelling, periarticular or joint-line tenderness, deformities with or without joint instability, muscle weakness and wasting in addition to occasional joint effusions, and palpable or even audible joint crepitus.

Common clinical presentations

The salient features of the common types of hip, knee, hand and nodal generalized OA are summarized in Table 15.3.

Table 15.3 Common clinical types/patterns of osteoarthritis

Hip OA commonly affects the superior pole of the joint. Typically, patients present with pain in the groin on exercise, but referred pain in the buttock, anterior thigh, knee and even the lower leg are not uncommon. With increasing severity it radiates down to the knee, is constant on exercise, and begins to cause stiffness and inability to reach down to tie shoe-laces. Pain begins to disturb sleep. Enjoyment of active hobbies is curtailed, and progression to joint destruction and fixed flexion contracture can be the end result in some patients. Characteristically, examination reveals an antalgic gait with painful restriction of internal rotation with the hip in flexion. Medial pole OA is less common. It occurs more frequently in women, is more frequently bilateral, and less frequently progresses. In patients with generalized nodal OA, the pattern of hip involvement is usually also medial or concentric. Bony destruction of the acetabulum or femoral head may lead to a ‘bobbing’ short-leg gait. A Trendelenburg gait is rare, but a coxalgic (Duchenne) gait is more common due to a desire to off-load the hip abductor muscles and hence reduce the joint reaction force, which is often three times body weight in single-leg stance. There is little to see apart from thigh wasting and, perhaps, fixed flexion. Tenderness is rare. Range of movement reveals a global deficit and fixed flexion; reduced adduction and internal rotation are often seen. Rotation is often the most ‘irritable’ of the movements.

Antero-posterior radiographs of the hip and pelvis should be inspected carefully to detect cardinal features of OA. Destructive arthropathy and avascular necrosis may be associated with non-steroidal anti-inflammatory drug (NSAID) therapy.

Knee OA commonly affects the medial and patello-femoral compartments of the joint, but may affect any of the three compartments. The medial compartment is most frequently affected, and leads to a varus deformity. Forces that occur on weight-bearing will pass medial to the knee and this increases point-loading in the medial compartment. Typically, patients present with anterior or medial knee pain aggravated by walking on uneven ground and by ascending or descending stairs. On examination they frequently have a characteristic antalgic gait and bilateral, symmetrical varus deformities. In some patients, knee OA is associated with generalized nodal OA. Unilateral knee OA, especially in men, may be a consequence of a previous injury, meniscus tear or complete meniscal resection.

Nodal OA is a clinically distinct form of primary generalized OA, with a strong genetic component. It is much more common in women than in men and characteristically affects the interphalangeal (IP) joints of the fingers (DIPJs > PIPJs) and the carpometacarpal joints of the thumbs. The onset, which is sometimes subacute with considerable pain, swelling and local inflammation, is often in the perimenopausal period, and may be triggered by oestrogen withdrawal and other endocrine changes at this time. Although multiple joints in both hands are frequently affected, the onset is typically episodic and additive in pattern, with each joint going through a sequence of changes over a number of months. Pain, soft-tissue swelling and tenderness are followed by the gradual development of hard, bony swellings on either side of the extensor tendons on the dorsal aspect of the fingers in relationship to the IP joints. Heberden nodes at the DIPJs are more frequent than Bouchard nodes at the PIPJs. Once the inflammation has settled, patients are left with relatively pain-free, knobbly fingers. Although the lesions can be associated with considerable deformity and subluxation, serious disability is unusual. In generalized nodal OA, osteophyte formation and subluxation of the first carpometacarpal joints results in characteristic ‘squaring’ of the hands, and the knees and other joints may be also affected. Rarely, in cases with a more acute onset (‘hot Heberden nodes’), the initial soft-tissue inflammation is associated with the development of cysts containing hyaluronate. Erosive OA is the name sometimes given to describe a rarer variant of nodal osteoarthritis, which is characterized by similar episodic symptoms and signs of local inflammation followed by the development of more destructive subchondral erosions associated with florid proliferation of bone, instability, and subluxation in the PIPJs and DIPJs.

Atypical and ‘secondary’ osteoarthritis

The possibility of some defined predisposing underlying condition (see Table 15.1) needs to be considered, particularly in patients who develop typical symptoms and signs of OA before the age of 40 years, in those who develop OA in joints that are usually not affected, and in those with certain characteristic patterns of joint involvement. A history of major preceding trauma, such as a fracture that resulted in articular cartilage damage or subsequent mal-alignment, is often found to be the cause of monoarticular OA developing at an early age or in a joint, such as the ankle, that is seldom otherwise affected. Nearly 50% of patients have knee OA 21 years after open meniscectomy, and the average time to develop hip OA following a fracture dislocation is 7 years. Early-onset OA with prominent involvement of the second and third metacarpophalangeal (MCP) joints is very characteristic in patients with haemochromatosis and may be an early clinical clue that leads to establishment of the diagnosis (for more details see Chapter 14). Although deposition of calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP or apatite) crystals is common in articular cartilage in OA, the possibility of familial CPPD disease should be considered in patients presenting with premature knee OA. This is especially important when the knee OA is accompanied by frequent inflammatory episodes or prominent hypertrophic radiographic features, and in patients presenting with OA in relatively atypical joints, such as the shoulder, elbow or radiocarpal joints in the wrists.

Investigations

Plain radiographs are used to assess the severity of the structural changes in patients with OA. Because radiographic evidence of OA is so frequent in asymptomatic middle-aged and elderly persons, it is important to consider the clinical features (symptoms and signs) when interpreting the results. Focal, rather than uniform, joint space narrowing and the presence of osteophytes are the main radiographic features, with subchondral bone sclerosis and cysts in more advanced cases. Ossified synovial loose bodies and chondrocalcinosis can also sometimes be detected on plain radiography. Standing radiographs are required to assess the extent to which joint space narrowing reflects loss of articular cartilage in the tibio-femoral joints.

Magnetic resonance imaging (MRI) is being developed for the earlier and more quantitative detection of articular cartilage changes, including changes in hydration and proteoglycan composition, but has yet to be refined and validated sufficiently to make it useful in clinical practice. This is also true of isotope scans with ⁹⁹Tc-labelled bisphosphonate, which in research studies have shown increased uptake of isotope in OA joints that subsequently go on to develop progressive structural changes. MRI is, however, useful for detecting intra-articular soft-tissue lesions, such as meniscus tears, and for the diagnosis of osteonecrosis. Bone scintigraphy is occasionally used for the detection of osteonecrosis, stress fractures and bone metastases but is increasingly being replaced by MRI.

Blood tests are not helpful in the diagnosis or management of OA and are used largely to exclude other diseases associated with systemic inflammation or metabolic abnormalities. For example, measurements of serum calcium and alkaline phosphatase are critical for the diagnosis of primary hyperparathyroidism and hypophosphatasia; measurement of serum ferritin is required for the diagnosis of haemochromatosis; and detection of homogentisic acid in the urine will confirm a diagnosis of ochronosis.

Although cartilage degradation products, such as hyaluronan, keratan sulphate and cartilage oligomeric protein, and cartilage synthesis markers, such as Type II collagen c-pro-peptide, have been shown to be increased in the plasma, synovial fluid or urine of patients with OA, there are currently no biochemical or molecular markers that have clinical utility for diagnosis, monitoring the progress of structural changes, or assessing the prognosis of OA in clinical practice.

Synovial fluid analysis in OA is really indicated only to exclude bacterial joint infection or gout. The fluid is usually clear and viscous with a low cell count. Detection of crystals by polarizing light microscopy is not helpful in distinguishing OA from primary calcium crystal deposition disorders, because crystals of CPPD and BCP are each detected in up to half of all effusions from patients with knee OA.

Management

Treatment is directed predominantly at relieving symptoms, maintaining and improving joint function, and minimizing disability and handicap. Optimal management of patients with all types of OA requires a combination of non-pharmacological and pharmacological modalities.

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