What is osteoarthritis?







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Osteoarthritis:
     Osteoarthritis (OA) is by far the most common form of arthritis and is a major cause of pain and osteosclerosis, osteophyte formation at the joint margin, and remodelling of joint contour with enlargement of affected joints.
Epidemiology
The prevalence rises progressively with age and it has been estimated that 45% of all people develop knee OA and 25% hip OA at some point during life. Although some are asymptomatic, the lifetime risk of having a total hip or knee replacement for OA in someone aged 50 is about 11% for women and 8% for men in the UK. There are major ethnic differences in susceptibility: the prevalence of hip OA is lower in Africa, China, Japan and the Indian subcontinent than in European countries, and that of knee OA is higher.
Pathophysiology
OA is a complex disorder with both genetic and environmental components (Box 24.36).



Genetic factors are recognized as playing a key role in the pathogenesis of OA. Family-based studies have estimated that the heritability of OA ranges from about 43% at the knee to between 60% and 65% at the hip and hand, respectively. In most cases, the inheritance is polygenic and mediated by several genetic variants of small effect.
      OA can, however, be a component of multiple epiphyseal dysplasias, which are caused by mutations in the genes that encode components of cartilage matrix. Structural abnormalities, such as slipped femoral epiphysis and developmental dysplasia of the hip, are also associated with a high risk of OA, presumably due to abnormal load distribution across the joint. Similar mechanisms probably explain the increased risk of OA in patients with limb deformity secondary to Paget’s disease of bone.
            Biomechanical factors play an important role in OA related to certain occupations, such as farmers (hip OA), miners (knee OA) and elite or professional athletes (knee and ankle OA). It has been speculated that the higher prevalence of knee OA in the Indian subcontinent and East Asia might be accounted for by squatting. There is also a high risk of OA in people who have had destabilising injuries, such as cruciate ligament rupture, and those who have had meniscetomy. For most individuals, however, participation in recreational sport does not appear to increase the risk significantly. There is a strong association between obesity and OA, particularly of the hip. This is thought to be due partly to biomechanical factors but it has also been speculated that cytokines released from adipose tissue may play a role.
           Oestrogen appears to play a role; lower rates of OA have been observed in women who use hormone replacement therapy (HRT), and women who receive aromatase inhibitor therapy for breast cancer often experience a flare in symptoms of OA.
                 Degeneration of articular cartilage is the defining feature of OA. Under normal circumstances, chondrocytes are terminally differentiated cells but in OA they start dividing to produce nests of metabolically active cells (Fig. 24.16A). Initially, matrix components are produced by these cells at an increased rate, but at the same time there is accelerated degradation of the major structural components of cartilage matrix, including aggrecan and type II collagen (see Fig. 24.5, p. 987).
             Eventually, the concentration of aggrecan in cartilage matrix falls and makes the cartilage vulnerable to load-bearing injury. Fissuring of the cartilage surface (‘fibrillation’) then occurs, leading to the development of deep vertical clefts (Fig. 24.16B), localised chondrocyte death and decreased cartilage thickness. This is initially focal, mainly targeting the maximum load-bearing part of the joint, but eventually large parts of the cartilage surface are damaged. Calcium pyrophosphate and basic calcium phosphate crystals often become deposited in the abnormal cartilage.
OA is also accompanied by abnormalities in subchondral bone, which becomes sclerotic and the site of subchondral cysts (Fig. 24.16C).



 Fibrocartilage is produced at the joint margin, which undergoes endochondral ossification to form osteophytes. Bone remodeling and cartilage thinning slowly alter the shape of the OA joint, increasing its surface area. It is almost as though there is a homeostatic mechanism operative in OA that causes enlargement of the failing joint to spread the mechanical load over a greater surface area. Patients with OA also have higher BMD values at sites distant from the joint and this is particularly associated with osteophyte formation. This is in keeping with observations made in epidemiological studies that show that patients with OA are partially protected from developing osteoporosis and vice versa. This is likely to be due to the fact that the genetic factors that predispose to osteoporosis might be protective for OA.
                   The synovium in OA is often hyperplastic and may be the site of inflammatory change, but to a much lesser extent than in RA and other inflammatory arthropathies. Osteochondral bodies commonly occur within the synovium, reflecting chondroid metaplasia or secondary uptake and growth of damaged cartilage fragments. The outer capsule also thickens and contracts, usually retaining the stability of the remodelling joint. The muscles surrounding affected joints commonly show evidence of wasting and non-specific type II fibre atrophy
Clinical features
         OA has a characteristic distribution, mainly targeting the hips, knees, PIP and DIP joints of the hands, neck and lumbar spine (see Fig. 24.10). The main presenting symptoms are pain and functional restriction. The causes of pain in OA are not completely understood but may relate to increased pressure in subchondral bone (mainly causing night pain), trabecular microfractures, capsular distension and low-grade synovitis. Pain may also result from bursitis and enthesopathy secondary to altered joint mechanics. Typical OA pain has the characteristics listed in Box 24.37.



 For many people, functional restriction of the hands, knees or hips is an equal, if not greater, problem than pain. The clinical findings vary according to severity but are principally those of joint damage.
The correlation between the presence of structural change, as assessed by imaging, and symptoms such as pain and disability varies markedly according to site. It is stronger at the hip than at the knee, and poor at most small joints. This suggests that the risk factors for pain and disability may differ from those for structural change. At the knee, for example, reduced quadriceps muscle strength and adverse psychosocial factors (anxiety, depression) correlate more strongly with pain and disability than the degree of radiographic change. Radiological evidence of OA is very common in middle-aged and older people, and the disease may coexist with other conditions, so it is important to remember that pain in a patient with OA may be due to another cause

Generalized nodal OA
                            Characteristics of this common form of OA are shown in Box 24.38.


Some patients are asymptomatic whereas others develop pain, stiffness and swelling of one or more PIP and DIP joints of the hands from the age of about 40 years onwards. Gradually, these develop posterolateral swellings on each side of the extensor tendon, which slowly enlarge and harden to become Heberden’s (DIP) and Bouchard’s (PIP) nodes (Fig. 24.17).



Typically, each joint goes through a phase of episodic symptoms (1–5 years) while the node evolves and OA develops. Once OA is fully established, symptoms may subside and hand function often remains good. Affected joints are enlarged as a result of osteophyte formation and often show characteristic lateral deviation, reflecting the asymmetric focal cartilage loss of OA (Fig. 24.18).



 Involvement of the first CMC joint is also common, leading to pain on trying to open bottles and jars, and functional impairment. Clinically, it may be detected by the presence of crepitus on joint movement, and squaring of the thumb base. Generalised nodal OA has a very strong genetic component: the daughter of an affected mother has a 1 in 3 chance of developing nodal OA herself. People with nodal OA are also at increased risk of OA at other sites, especially the knee
. Knee OA
                    At the knee, OA principally targets the patello-femoral and medial tibio-femoral compartments but eventually spreads to affect the whole of the joint (Fig. 24.19).



It may be isolated or occur as part of generalised nodal OA. Most patients have bilateral and symmetrical involvement. In men, trauma is often a more important risk factor and may result in unilateral OA. The pain is usually localised to the anterior or medial aspect of the knee and upper tibia. Patello-femoral pain is usually worse going up and down stairs or inclines. Posterior knee pain suggests the presence of a complicating popliteal cyst (Baker’s cyst). Prolonged walking, rising from a chair, getting in or out of a car, or bending to put on shoes and socks may be difficult.
Local examination ndings may include:
• a jerky, asymmetric (antalgic) gait with less time weightbearing on the painful side
• a varus (Fig. 24.20) or, less commonly, valgus and/or a fixed flexion deformity
• joint-line and/or periarticular tenderness (secondary anserine bursitis and medial ligament enthesopathy (see Box 24.25), causing tenderness of the upper medial tibia)
 • weakness and wasting of the quadriceps muscle
• restricted flexion and extension with coarse crepitus
 • bony swelling around the joint line.



CPPD crystal deposition in association with OA is common at the knee. This may result in a more overt inflammatory component (stiffness, effusions) and super-added acute attacks of synovitis (‘pseudogout’; p. 1016), which may be associated with more rapid radiographic and clinical progression.
Hip OA
Hip OA most commonly targets the superior aspect of the joint (Fig. 24.21).



It is often unilateral at presentation, frequently progresses with superolateral migration of the femoral head, and has a poor prognosis. The less common central (medial) OA shows more central cartilage loss and is largely confined to women. It is often bilateral at presentation and can be associated with generalised nodal OA. It has a better prognosis than superior hip OA and progression to axial migration of the femoral head is uncommon.
The hip shows the best correlation between symptoms and radiographic change. Hip pain is usually maximal deep in the anterior groin, with variable radiation to the buttock, anterolateral thigh, knee or shin. Lateral hip pain, worse on lying on that side with tenderness over the greater trochanter, suggests secondary trochanteric bursitis. Common functional difficulties are the same as for knee OA; in addition, restricted hip abduction in women may cause pain during sexual intercourse. Examination may reveal:
• an antalgic gait                                                                                                                                 
 • weakness and wasting of quadriceps and gluteal muscles
 • pain and restriction of internal rotation with the hip  flexed – the earliest and most sensitive sign of hip OA; other movements may subsequently be restricted and painful
 • anterior groin tenderness just lateral to the femoral pulse • fixed flexion, external rotation deformity of the hip
 • ipsilateral leg shortening with severe joint attrition and superior femoral migration.
Obesity is associated with more rapid progression of hip OA.
Spine OA
The cervical and lumbar spine are the sites most often targeted by OA, where it is referred to as cervical spondylosis and lumbar spondylosis, respectively (Fig. 24.22).



Spine OA may occur in isolation or as part of generalised OA. The typical presentation is with pain localised to the low back region or the neck, although radiation of pain to the arms, buttocks and legs may also occur due to nerve root compression. The pain is typically relieved by rest and worse on movement. On physical examination, the range of movement may be limited and loss of lumbar lordosis is typical. The straight leg-raising test or femoral stretch test may be positive and neurological signs may be seen in the legs where there is complicating spinal stenosis or nerve root compression.
Early-onset OA
Unusually, typical symptoms and signs of OA may present before the age of 45. In most cases, a single joint is affected and there is a clear history of previous trauma. However, specific causes of OA need to be considered in people with early-onset disease affecting several joints, especially those not normally targeted by OA, in which case rare causes need to be considered (Box 24.39). Kashin–Beck disease is a rare form of OA that occurs in children, typically between the ages of 7 and 13, in some regions of China. The cause is unknown but suggested predisposing factors are selenium deficiency and contamination of cereals with mycotoxin-producing fungi.



Erosive OA
This term is used to describe an unusual group of patients with hand OA who have a more prolonged symptom phase, more overt inflammation, more disability and worse outcome than those with nodal OA. Distinguishing features include preferential targeting of PIP joints, subchondral erosions on X-rays, occasional ankylosis of affected joints and lack of association with OA elsewhere. It is unclear whether erosive OA is part of the spectrum of hand OA or a discrete subset.
 Investigations
A plain X-ray of the affected joint should be performed and often this will show one or more of the typical features of OA (see Figs 24.18–24.22). In addition to providing diagnostic information, X-rays are of value in assessing the severity of structural change, which is helpful if joint replacement surgery is being considered. Non-weight-bearing posteroanterior views of the pelvis are adequate for assessing hip OA. Patients with suspected knee OA should have standing anteroposterior X-rays taken to assess tibio-femoral cartilage loss, and a flexed skyline view to assessing patellofemoral involvement. Spine OA can often be diagnosed on a plain X-ray, which typically shows evidence of disc space narrowing and osteophytes. If nerve root compression or spinal stenosis is suspected, MRI should be performed
.                    Routine biochemistry, hematology and autoantibody tests are usually normal, though OA is associated with a moderate acute phase response. Synovial fluid aspirated from an affected joint is viscous with a low cell count. Unexplained early-onset OA requires additional investigation, guided by the suspected underlying condition. X-rays may show typical features of dysplasia or avascular necrosis, widening of joint spaces in acromegaly, multiple cysts, chondrocalcinosis and MCP joint involvement in hemochromatosis (p. 895), or disorganized architecture in neuropathic joints.
 Management
Treatment follows the principles outlined on pages 1000–1007. Measures that are pertinent in older people are summarised in Box 24.40.



Education
It is important to explain the nature of the condition fully, outlining the role of relevant risk factors such as obesity, heredity, and trauma. The patent should be informed that established structural changes are permanent and that, although a cure is not possible at present, pain and function can often be improved. The prognosis should also be discussed, mentioning that it is generally good for nodal hand OA and better for knee than hip OA.
 Lifestyle advice
               Weight loss has a substantial beneficial effect on symptoms if the patient is obese and is probably one of the most effective treatments available for OA of the lower limbs. Strengthening and aerobic exercises also have beneficial effects in OA and should be advised, preferably with reinforcement by a physiotherapist (see Box 24.27). Quadriceps strengthening exercises are particularly beneficial in knee OA. Shock-absorbing footwear, the pacing of activities, the use of a walking stick for painful knee or hip OA, and the provision of built-up shoes to equalize leg lengths can all improve symptoms.
Non-pharmacological therapy
                     Acupuncture and transcutaneous electrical nerve stimulation (TENS) have been shown to be effective in knee OA. Local physical therapies, such as heat or cold, can sometimes give temporary relief.
 Pharmacological therapy                               
                    If symptoms do not respond to non-pharmacological measures, paracetamol should be tried. The addition of a topical NSAID, and then capsaicin, for knee and hand OA can also be helpful. Oral NSAIDs should be considered in patients who remain symptomatic. These drugs are significantly more effective than paracetamol and can be successfully combined with paracetamol or compound analgesics if the pain is severe. Strong opiates may occasionally be required. Anti neuropathic drugs, such as amitriptyline, gabapentin, and pregabalin, are sometimes used in patients with symptoms that are difficult to control but the evidence base for their use is poor. Neutralizing antibodies to nerve growth factors have been developed and are a highly effective treatment for pain in OA but they are not yet licensed for routine clinical use.
Intra-articular injections
                     Intra-articular glucocorticoid injections are effective in the treatment of knee OA and are also used for symptomatic relief in the treatment of OA at the first CMC joint. The duration of effect is usually short but trials of serial glucocorticoid injections every 3 months in knee OA have shown efficacy for up to 1 year. Intra-articular injections of hyaluronic acid are effective in knee OA but the treatment is expensive and the effect short-lived. In the UK they have not been considered to be cost-effective by NICE.
 Neutraceuticals           
                  Chondroitin sulfate and glucosamine sulfate have been used alone and in combination for the treatment of knee OA. There is evidence from randomized controlled trials that these agents can improve knee pain to a small extent (3–5%) compared with placebo.
Surgery
             Surgery should be considered for patients with OA whose symptoms and functional impairment impact significantly on their quality of life despite optimal medical therapy and lifestyle advice. Total joint replacement surgery is by far the most common surgical procedure for patients with OA. It can transform the quality of life for people with severe knee or hip OA and is indicated when there is significant structural damage on X-ray. Although surgery should not be undertaken at an early stage during the development of OA, it is important to consider it before functional limitation has become advanced since this may compromise outcome. Patient-specific factors, such as age, gender, smoking and presence of obesity, should not be barriers to referral for joint replacement.
Only a small proportion of patients with OA progress to the extent that total joint replacement is required but OA is by far the most frequent indication for this. Over 95% of joint replacements continue to function well into the second decade after surgery and most provide a life-long, pain-free function. Up to 20% of patients are not satisfied with the outcome, however, and a few experiences little or no improvement in pain. Other surgical procedures are performed much less frequently. Osteotomy is occasionally carried out to prolong the life of malaligned joints and to relieve pain by reducing intraosseous pressure. Cartilage repair is sometimes performed to treat focal cartilage defects resulting from joint injury.
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