- Email: [email protected]
Osteoarthritis
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Seminar
Osteoarthritis Paul Creamer, Marc C Hochberg Osteoarthritis is the most common form of arthritis. Osteoarthritis is a major cause of morbidity and disability as well as a burden on health-care resources, especially for the elderly. There have been advances in our understanding of this condition. No longer is osteoarthritis regarded as a simple consequence of ageing and cartilage degeneration; indeed, the former diagnostic label of degenerative joint disease is now recognised to be a misnomer. Rather, the pathological changes of osteoarthritis are seen as the result of active processes, many of which may be reparative rather than destructive in nature. In addition, osteoarthritis may not be a single disorder, but rather a group of overlapping distinct diseases. Risk factors, pathophysiology, clinical features and outcome vary from site to site, leading to the suggestion of osteoarthritic disorders as a more appropriate label.1 While aiming to be comprehensive, we will stress those areas in which most recent advances have been made.
Epidemiology A single definition of osteoarthritis remains elusive. A workshop held in 1995 proposed the following consensus definition: “Osteoarthritic diseases are a result of both mechanical and biologic events that destabilize the normal coupling of degradation and synthesis of articular cartilage chondrocytes and extracellular matrix, and subchondral bone. Although they may be initiated by multiple factors, including genetic, developmental, metabolic, and traumatic, osteoarthritis diseases involve all of the tissues of the diarthrodial joint. Ultimately, osteoarthritis diseases are manifested by morphologic, biochemical, molecular, and biomechanical changes of both cells and matrix which lead to a softening, fibrillation, ulceration, loss of articular carilage, sclerosis and eburnation of subchondral bone, osteophytes, and subchondral cysts. When clinically evident, osteoarthritis diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects.”1 A classification schema for primary and secondary osteoarthritis has been developed by the American College of Rheumatology (panel 1),2 as have classification criteria for osteoarthritis of the hand, hip, and knee.3 These latter criteria are most useful in clinical research, especially as Lancet 1997; 350: 503–09 Geriatric Research Education and Clinical Center, Maryland Veterans Affairs Health Care System, Baltimore (Prof M C Hochberg MD); and Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA (M C Hochberg, P Creamer MD) Correspondence to: Prof Marc C Hochberg, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland at Baltimore, MSTF Room 8–34, Baltimore, MD 21201, USA
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Panel 1: Classification of osteoarthritis2 ● Idiopathic Localised (eg, hands, feet, knees, hips, and other single sites) Generalised (three or more joint groups listed above) ● Secondary Post-traumatic Congenital or developmental diseases Localised (eg, hip dysplasia) Generalised (eg, chondrodysplasias, inherited metabolic diseases [ochronosis, haemochromatosis]) Calcium-deposition disease Other bone and joint disorders (eg, avascular necrosis, rheumatoid arthritis, Paget’s disease) ● Other diseases Endocrine diseases (eg, acromegaly, hyperparathyroidism) Neuropathical (Charcot’s) arthropathy Miscellaneous
inclusion criteria for clinical trials, rather than for case definition in epidemiological studies. Most epidemiological studies have defined cases of osteoarthritis based on the presence of typical radiographic features as originally described by Kellgren and Lawrence in 1957. The ability to compare epidemiological studies, especially those that estimate prevalence in different populations, is limited by variability in the accuracy of reading radiographs as well as other factors.4 In populations of white North Americans and Northern Europeans, about one-third of adults aged 25-74 years have features of radiographic osteoarthritis involving at least one peripheral joint group: the most common sites are the hands, followed by feet, knees, and hips. Much is known about the risk factors for radiographic osteoarthritis (panel 2, figure 1), and some studies suggest that they differ not only from joint to joint but also at different sites within the same joint (eg, patellofemoral vs tibiofemoral compartment of the knee joint).5 Furthermore, the principal risk factors for radiographic knee osteoarthritis (age, female sex, obesity, and joint trauma) are not the same as those reporting knee pain (psychosocial factors, general health status).6,7 Age is the strongest determinant of osteoarthritis with prevalence rates for all joints rising with increasing age. Incidence rates also rise with age but there is some evidence that this reaches a plateau in the seventh decade. The mechanism by which age predisposes to osteoarthritis is unclear. It is tempting to speculate that biochemical changes within aging cartilage render it more susceptible to damage and degradation but evidence to support this is lacking. Women are at higher risk of developing osteoarthritis than men, particularly after the menopause. While the biochemical effects of sex hormones on cartilage metabolism are complex and in-vitro and in-vivo animal studies have produced conflicting results; most epidemiological studies suggest that hormone-replacement therapy confers a protective effect on the development of 503
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Panel 2: Factors associated with osteoarthritis* ● Genetic factors Sex Inherited disorders of type II collagen (eg, Stickler’s syndrome) Mutations in the type II collagen gene (ie, COL2A1) Other inherited disorders of bones and joints Race/ethnicity ● Non-genetic host factors Increasing age Overweight Depletion of female sex hormones (eg, postmenopausal state) (?) Developmental and acquired bone and joint diseases Previous joint surgery (eg, meniscectomy) Race/ethnicity ● Environmental factors Occupations and physical demands of work Major trauma to joints Leisure and/or sports activities *Reproduced, with permission, from reference 9.
knee and hip osteoarthritis.8 The effects of sex hormones on cartilage may vary with menopausal status and stage of osteoarthritis. Obesity has been strongly linked to osteoarthritis of the knee and, to a lesser extent, the hip, in cross-sectional and prospective studies.9 Obesity may act by increasing mechanical stress in weight-bearing joints, but because women are more susceptible to the risks of obesity than men and because obesity may be a risk factor for osteoarthritis in the hand, systemic factors are also thought to be involved. Several studies in England and Sweden have focused on the role of occupation and sporting activity as risk factors for hip and knee osteoarthritis. Jobs involving kneeling, squatting, and climbing stairs are associated with higher rates of knee osteoarthritis, while jobs which require heavy lifting, including farming, are associated with higher rates
of hip osteoarthritis.9 Participation in sport has also been associated with an increased risk of lower-limb osteoarthritis. However, recreational physical activity, such as jogging, does not appear to increase the risk of osteoarthritis as long as the joints being subjected to repetitive stress are biomechanically normal. Although a hereditary component to osteoarthritis, particularly generalised osteoarthritis with Heberden’s nodes, has long been recognised, a recent study of female twin pairs showed significant heritability for radiographic features of osteoarthritis at the knee and hip.10 Although mutations in the gene for type II collagen (COL2A1) have been associated with early polyarticular osteoarthritis with mild chondrodysplasia, it is unlikely that there is a single gene for a structural component of cartilage that fully explains the genetic contribution to osteoarthritis.
Pathogenesis Osteoarthritis is generally seen as a disease of articular cartilage although it is clear that changes in subchondral bone are also important. Indeed, in idiopathic osteoarthritis, it remains unknown whether the initial abnormality occurs in the articular cartilage or the subchondral bone. Articular cartilage has two main functions: absorbing stress by deforming under mechanical load and providing a smooth load bearing surface to permit low-friction movement of the joint. The functional properties of cartilage result from its unique structure of chondrocytes embedded in a matrix of collagen and proteoglycan. The major structural protein is type II collagen, which consists of a triple helix of hydrophilic chains. The importance of type-II collagen is exemplified by the effect of mutations in the COL2A1 gene, but type-II collagen is also important in its ability to bind other matrix macromolecules, most notably types IX and XI collagen which, though present in small amounts, are critical for cartilage stability. The other major component of cartilage is proteoglycan, mainly
Figure 1: Aetiopathogenesis of osteoarthritis
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present as a large macromolecule called aggrecan. Aggrecan consists of a protein core to which many chondroitin and keratan-sulphate chains are attached, the core itself being attached to the hyaluronan skeleton via a link protein. Aggrecan is highly hydrophilic but also of low viscosity, ideally suited to its function of load dispersal. The gene for human aggrecan has been cloned and sequenced, and a preliminary study has shown an association between a polymorphism in this gene with polyarticular hand osteoarthritis in elderly men.11 Cartilage matrix turnover is a process of synthesis and degradation, which is balanced in healthy individuals. One view of osteoarthritis is as a failure to maintain this homeostatic balance, because of reduced formation or increased catabolism (figure 1). For example, matrix metalloproteinases—enzymes that catalyse both collagen and proteoglycan degradation including collagenase, gelatinase, and stromelysin—are found in increased concentrations in osteoarthritis cartilage, and their synthesis by chondrocytes can be stimulated by interleukin 1 (IL-1).12 Furthermore, blockage of these enzymes by doxycycline or chemically modified tetracyclines, at least in animal models, can reduce the severity of osteoarthritis lesions.13 Synthesis of cartilage components, on the other hand, appears to be dependent on a number of growth factors including insulin-like growth-factor 1 (IGF-1) and transforming growth-factor  (TGF). Although IGF-1 has been shown to reduce the development of osteoarthritis in animal models, evidence of a role for IGF-1 in human beings is conflicting: increased, reduced, and normal concentrations have been described in patients with osteoarthritis. The picture is equally confused with TGF. Much of this work has been done in vitro or in animal models and caution is needed when extrapolating to adult human beings. Subchondral bone changes are often seen on radiographs in patients with established osteoarthritis and increasingly these are viewed as an important cause of osteoarthritis rather than the sequelae of cartilage damage. It is known, for example, that the integrity of overlying cartilage depends on the mechanical properties of its bony bed. One model of osteoarthritis suggests that stiffening of subchondral bone, perhaps after repetitive microfractures, results in bone that is no longer effective as a shock absorber. Indirect evidence supporting a role for subchondral-bone turnover in osteoarthritis comes from: in-vivo studies of the guinea-pig model where changes in subchondral bone occur before cartilage changes are apparent;14 increased bone expression of matrix metalloproteinases and alkaline phosphatase in human hip osteoarthritis;15 and prospective studies in which bone changes as detected by scintigraphy have been shown to predict radiographic progression at both the hand and the knee.16 Evidence of the importance of bone also comes from the inverse association between osteoarthritis and diseases of low mineral density, most notably osteoporosis.17 Bone mineral density in patients with radiographic features of hip osteoarthritis is higher than in patients with normal radiographs, even after adjusting for body weight, not only in areas close to joints affected by osteoarthritis but also in sites away from these joints.18 The role of inflammation in the pathogenesis of osteoarthritis remains controversial. An inflammatory component may be present in osteoarthritis, at least in some patients at some phases of the disease. For example, there may be clear synovial hyperplasia and a dense Vol 350 • August 16, 1997
Panel 3: Symptoms and signs in patients with osteoarthritis ● Symptoms Joint pain Morning stiffness Gel phenomenon Buckling/instability Loss of function ● Signs Bony enlargement Limitation of range of motion Crepitus on motion Tenderness on pressure Pain on motion Joint effusion Malalignment, joint deformity, or both
mononuclear cell infiltrate, indistinguishable from that seen in rheumatoid arthritis.19 Such inflammation is focal, being most pronounced where the synovium is adjacent to cartilage.20 Expression of oncoproteins21 and nuclear factor (NF)B,22 an essential transcription factor for expression of various proinflammatory genes, have been found in osteoarthritis synovium. Nitric oxide synthase has also been found in chondrocytes from cartilage affected by osteoarthritis, and human articular chondrocytes, when stimulated by cytokines such as IL-1, release inflammatory mediators including nitric oxide.23 Nitric oxide may be directly toxic to articular cartilage; suggested mechanisms include down regulation of IL-1 receptor antagonist synthesis and induction of apoptosis of chondrocytes. Finally, systemic markers of inflammation such as Creactive protein are raised in many patients if a sensitive assay is used.24 The cause of inflammation in osteoarthritis remains unclear. Calcium pyrophosphate crystals can be shown to worsen the development of osteoarthritis in rabbit models,25 but their role and that of other crystals, such as basic calcium apatite, in human osteoarthritis is controversial.26 Once initiated, the release of wear particles may contribute to a cycle of inflammation resulting in further activation of synovium and release of cytokines. Although inflammation can be an important part of healing and repair, in the context of osteoarthritis it is generally regarded as harmful: in animal models, for example, the degree of inflammation correlates with the amount of cartilage loss. Inflammation may contribute to cartilage loss via production of inflammatory cytokines such as IL-1, which in turn result in release of matrix metalloproteinases, such as collagenases and stromelysin, as well as prostaglandins and plasminogen activators.27 Finally, in the dog model of osteoarthritis, the intraarticular administration of IL-1 receptor antagonist reduces the expression of collagenase and the subsequent development of osteoarthritis.28
Clinical features The clinical features of osteoarthritis are summarised in panel 3. Pain is the most important symptom which brings the patient to the doctor’s surgery; it is usually insidious in onset, mild-to-moderate in intensity, worsened by use of the involved joint, and improved with rest. Pain at rest or during the night are features of severe disease. Possible sources and causes of pain in patients with osteoarthritis include the synovial membrane, joint capsule, periarticular ligaments, periarticular muscle spasm, periosteum, and 505
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subchondral bone. Several observations strongly suggest as functional limitation and reduced quality of life may also that pain in patients with osteoarthritis is not simply the be included in trials.29 Systematic reviews of both nonresult of structural changes in the affected joint, but, rather, pharmacological33 and pharmacological therapy of lowerthe outcome of a complex interplay between structural limb osteoarthritis,34,35 as well as guidelines for the change, peripheral and central pain processing management of lower-limb osteoarthritis, have been mechanisms, and subjective differences in what constitutes published.36-38 A pyramid approach to the management of pain, which in turn are influenced by culture, sex, and patients with osteoarthritis is illustrated in figure 2. It is psychosocial factors.7 Indeed, although reporting of pain is important for the practitioner to recognise that the layers of significantly associated with the presence of radiographic the pyramid are added one to another in a stepwise fashion features of osteoarthritis in the general population, there is during the course of managing the individual patient (eg, a poor correlation between severity of pain and radiographic NSAIDs can be added on in lower dosages to a regimen features of osteoarthritis in patients. Nonetheless, valid and consisting of paracetamol and topical capsaicin, or intrareliable measures, including the Western Ontario McMaster articular corticosteroid injections can be given to patients Osteoarthritis Index, are now available to measure pain in already on paracetamol, NSAIDs, or both). clinical trials and outcome studies.29 Treatment should be individualised and based on the The clinical diagnosis of osteoarthritis is usually distribution and severity of joint involvement as well as the confirmed by the finding of typical radiographic changes presence of comorbid conditions. Education of patients, of osteoarthritis including marginal osteophytes, social support, and counselling are often beneficial. asymmetrical joint-space narrowing, subchondral bone Arthritis charities, such as the Arthritis and Rheumatism sclerosis, subchondral cyst formation and, in severe Council in the UK, the Arthritis Foundation in the cases, deformity of bone ends. Juxta-articular USA, and the Arthritis Society in Canada publish osteoporosis and marginal erosions, seen in brochures on education for patients and often patients with rheumatoid arthritis, are not a organise local self-help groups. Formal feature of osteoarthritis. Routine laboratory interventions include self-management tests, including complete blood count and programmes, such as the arthritis self-help chemistry panel, are usually normal. These and cognitive behavioural course39 laboratory tests should be obtained before approaches, designed to teach patients beginning therapy with a non-steroidal ways of coping with their pain.40 anti-inflammatory drug (NSAID) and Physical therapy has an important at annual intervals in patients on role in the management of long-term NSAID therapy.30 patients with osteoarthritis, The natural history of including instruction in muscle osteoarthritis is highly variable.16 strengthening exercises and Most studies have been done participation in aerobic in patients with knee osteoexercise programmes. arthritis, although some Quadriceps strengthening have included patients with exercises and aerobic Figure 2: Pyramid approach to the management of osteoarthritis hand and hip osteoarthritis.31 exercises have both been It is clear that, although shown to be effective in radiographic progression is reducing pain and usual, it is by no means inevitable, and a proportion of improving function in patients with knee osteoarthritis in patients with established osteoarthritis do not show further studies of up to 6 months.33 The technique for quadriceps progression on follow-up over several years. For example, strengthening is illustrated in figure 3. The patient is in a prospective observational study of 188 outpatients with instructed to lie on their back with one knee bent and the knee osteoarthritis, followed up for 1-5 years, 28% showed other leg straight with the ankle dorsiflexed to 90º. The no change in any radiographic feature.32 Some joints even quadriceps muscle of the straight leg is tightened and, appear to improve with apparent recovery of joint space, while keeping the knee straight, the leg is raised about 25though the degree to which this represents true cartilage 50 cm off the ground. The leg is held up for 10 s and then regrowth or simply an artefact of radiographic technique is lowered and the muscle relaxed. The exercise is repeated at not known. Similarly, pain, and less often function, can also least ten times alternating legs. improve. Changes on radiographs are often discordant with A multicentre study, by Ettinger and colleagues,41 that changes in pain; thus, radiographs may not be the most lasted 18 months showed that aerobic or resistive exercise appropriate outcome measure when designing intervention got better results than education for patients alone when studies in osteoarthritis. combined with standard pharmacological therapy in Certain features are now known to predict radiographic patients with knee osteoarthritis and mild disability. Data progession. In addition to abnormal bone scintigraphy, from well designed clinical trials support the routine these include obesity, presence of generalised osteoarthritis recommendation of exercise programmes in patients with with Heberden’s nodes, presence of chondrocalcinosis, and knee osteoarthritis. Occupational therapy may also be of raised serum concentrations of markers such as C-reactive value to patients to help them adapt to functional protein and hyaluronate.16 limitations by teaching them to do day-to-day activities. Weight reduction has been shown to reduce the risk of Management developing symptomatic knee osteoarthritis in an epidemiological study by Felson and colleagues,42 and to be Current treatment of osteoarthritis is purely to control associated with a reduction in both pain and impaired symptoms because as yet there are no disease-modifying function in overweight postmenopausal women with knee osteoarthritis drugs. The principal measure of treatment osteoarthritis.43 Diet counselling should also be a part of efficacy is traditionally pain, though other outcomes, such
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routine management for all overweight patients with moderate-to-severe lower-limb osteoarthritis in the past 20 osteoarthritis. years. With advances in prosthesis design, the rate of The main indication for drug therapy in osteoarthritis is revision due to loosening has fallen. pain. The drug of choice is currently paracetamol, which should be given at full dose for a reasonable time before Future other drugs are considered. A variable proportion of The understanding of the osteoarthritic disorders has patients will not respond to treatment and appear to derive increased over the past decade. The development of additional benefit from NSAIDs. It is reasonable to try selective cyclooxygenase-2 inhibitors may provide safer NSAIDs if non-pharmacological therapy and paracetamol NSAIDs which will improve the management of symptoms have failed to provide adequate symptom relief. There is no in patients with osteoarthritis.46,47 Studies of several novel clear evidence to suggest agents, including chemically superiority of one NSAID over modified tetracyclines and other another; however, indometacin metalloproteinase inhibitors, should not be used because of and IL-1 receptor antagonists greater comparative toxicity in have the potential to reverse the clinical trials.34,35 In addition, a structural or biochemical meta-analysis, by Henry and abnormalities of osteoarthritis found that Figure 3: Quadriceps strengthening exercise colleagues,44 are currently being investigated. piroxicam, ketoprofen, tolmetin In addition, autologous sodium, and azapropazone cartilage transplantation may be were associated with greater useful in patients with early risk of serious gastrointestinal complications such as disease and focal cartilage defects. Hopefully, these advances perforation, ulcers, and bleeds than other NSAIDs, will alter the prognosis and improve the quality of life for especially low-dose ibuprofen. General principles of patients with osteoarthritis in the coming century. NSAIDs used in osteoarthritis include: use of the PC is the recipient of a Travelling Postdoctoral Fellowship from the Arthritis minimum effective dose; avoidance of using more than one and Rheumatism Council, UK. NSAID simultaneously; assessment of benefit after about References 1 month (and cessation if no benefit is seen); and 1 Kuettner K, Goldberg VM. Osteoarthritic disorders. Rosemont: encouragement of intelligent non-compliance, such that American Academy of Orthopaedic Surgeons, 1995. the patient does not take medication if no pain is felt. 2 Altman R, Asch E, Bloch D, et al. Development of criteria for the Topical creams, either a NSAID or capsaicin, can be classification and reporting of osteoarthritis: classification of helpful as either monotherapy or when added to oral osteoarthritis of the knee. Arthritis Rheum 1986; 29: 1039–49. 3 Altman R. Classification of disease: osteoarthritis [suppl]. Semin Arthritis analgesics, especially if only one or more joints are involved. Rheum 1991; 20 (2): 40–47. In addition, topical creams give the patient a measure of 4 Spector TD, Hochberg MC. Methodological problems in the self control over their therapy which may itself be epidemiological study of osteoarthritis. Ann Rheum Dis 1994; 53: 43–46. beneficial. 5 Cooper C, McAlindon T, Snow S, et al. Mechanical and constitutional risk factors for symptomatic knee osteoarthritis: differences between Intra-articular steroids are widely used in osteoarthritis, medial tibiofemoral and patellofemoral disease. J Rheumatol particularly for the knee. There is some evidence to support 1994; 21: 307–13. their efficacy, but only for 1–3 weeks; triamcinolone 6 Davis M, Ettinger W, Neuhaus J, Barclay J, Degal M. Correlates of knee 45 hexacetonide is the most efficacious preparation. This pain among US adults with and without radiographic knee osteoarthritis. J Rheumatol 1992; 19: 1943–49. short efficacy is not reflected in clinical practice in which 7 Creamer P, Hochberg MC.Why does osteoarthritis of the knee hurt— some patients seem to have a sustained response to intrasometimes? Br J Rheumatol 1997; 37: 726–28. articular steroid. Efforts to identify predictors of response 8 Nevitt MC, Felson DT. Sex hormones and the risk of osteoarthritis in have proved largely unsuccessful. women: epidemiological evidence. Ann Rheum Dis 1996; 55: 673–76. 9 Hochberg MC, Lethbridge-Cejku M. Epidemiologic considerations in Intra-articular hyaluronic acid has also been shown to be the primary prevention of osteoarthritis. In: Hamerman D, ed. effective in patients with knee osteoarthritis; this therapy Osteoarthritis: public health implications for an aging population. requires weekly injections for 3–5 weeks and is more Baltimore: Johns Hopkins University Press, 1997: 169–86. efficacious than a single injection of intra-articular steroids. 10 Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin study. BMJ 1996; 312: 940–44. Patients whose pain is not adequately controlled by the 11 Horton W, Balakir R, Precht P, et al. Association between an aggrecan above measures may benefit from the judicious use of polymorphic allele and bilateral hand osteoarthritis in elderly white men: narcotic analgesics; however, controlled studies of these data from the Baltimore Longitudinal Study of Aging [suppl]. Arthritis Rheum 1996; 39 (9): 167. agents in patients with osteoarthritis are lacking and one 12 Woessner J Jr.The family of matrix metalloproteinases. Ann N Y Acad Sci must be concerned with the potential for long-term abuse. 1994; 732: 11–21. Tidal lavage with saline is effective in some patients with 13 Ryan ME, Greenwald RA, Golub LM. Potential of tetracyclines to knee osteoarthritis that has not responded to standard modify cartilage breakdown in osteoarthritis. Curr Opin Rheumatol 1996; 8: 238–47. medical therapy and is particularly useful in those for 14 Watson PJ, Hall LD, Malcolm A,Tyler JA. Degenerative joint disease in whom surgery is not recommended or refused. This can be the guinea pig: use of magnetic resonance imaging to monitor done with a needle arthroscope or even a sterile disposable progression of bone pathology. Arthritis Rheum 1996; 39: 1327–37. 14-gauge cannula, thereby avoiding the need for operating 15 Mansell JP,Tarlton JF, Bailey AJ. Biochemical evidence for altered subchondral bone collagen metabolism in osteoarthritis of the hip. theatre and general anaesthesia. The mechanism of action Br J Rheumatol 1997; 36: 16–19. of lavage is unknown; removal of wear particles and debris, 16 Hochberg MC. Prognosis of osteoarthritis. Ann Rheum Dis 1996; and removal of inflammatory mediators have all been 55: 685–88. suggested. 17 Star V, Hochberg MC. Osteoporosis in patients with rheumatic diseases. Rheum Dis Clin North Am 1994; 20: 561–76. Total joint replacement is an excellent treatment for 18 Nevitt MC, Lane NE, Scott JC, et al. Radiographic osteoarthritis of the osteoarthritis and has been responsible for a dramatic hip and bone mineral density: the Study of Osteoporotic Fractures improvement in the quality of life of individuals with Research Group. Arthritis Rheum 1995; 38: 907–16.
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THE LANCET 19 Haraoui B, Pelletier JP, Cloutier JM, Faure MP, Martel-Pelletier J. Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis. Arthritis Rheum 1991; 34: 153–63. 20 Lindblad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum 1987; 30: 1081–88. 21 Roivainen A, Soderstrom KO, Pirila L, et al. Oncoprotein expression in human synovial tissue: an immunohistochemical study of different types of arthritis. Br J Rheumatol 1996; 35: 933–42. 22 Marok R,Winyard PG, Coumbe A, et al. Activation of the transcription factor nuclear factor-B in human inflamed synovial tissue. Arthritis Rheum 1996; 39: 583–91. 23 Amin AR, DiCesare PE,Vyas P, et al.The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase. J Exp Med 1995; 182: 2097–102. 24 Spector TD, Hart DJ, Nandra D, et al. Low level increases in serum Creactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 1997; 40: 723–27. 25 Fam AG, Morava-Protzner I, Purcell C,Young BD, Bunting PS, Lewis AJ. Acceleration of experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis. Arthritis Rheum 1995; 38: 201–10. 26 Schumacher HR Jr. Synovial inflammation, crystals, and osteoarthritis [suppl]. J Rheumatol 1995; 20 (43): 101–03. 27 Belcher C, Fawthrop F, Bunning R, Doherty M. Plasminogen activators and their inhibitors in synovial fluids from normal, osteoarthritis, and rheumatoid arthritis knees. Ann Rheum Dis 1996; 55: 230–36. 28 Caron JP, Fernandes JC, Martel-Pelletier J, et al. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis: suppression of collagenase-1 expression. Arthritis Rheum 1996; 39: 1535-44. 29 Bellamy N, Kirwan J, Boers M, et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip and hand OA: consensus development at OMERACT III. J Rheumatol 1977; 24: 799–802. 30 American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996; 39: 723–31. 31 Dieppe PA, Cushnaghan J, Shepstone L.The Bristol “OA500” study: progression of osteoarthrits (OA) over 3 years and the relationship between clinical and radiographic features at the knee joint. Osteoarthritis Cartilage 1997; 5: 87–97. 32 Ledingham J, Regan M, Jones A, Doherty M. Factors affecting radiographic progression of knee osteoarthritis. Ann Rheum Dis 1995; 54: 53–8.
33 Puett DW, Griffin MR. Published trials of nonmedicinal and noninvasive therapies for hip and knee osteoarthritis. Ann Intern Med 1994; 121: 133–40. 34 Towheed TE, Hochberg MC. A systematic review of randomized controlled trials of pharmacologic therapy in osteoarthritis of the hip. J Rheumatol 1997; 24: 549–57. 35 Towheed TE, Hochberg MC. A systematic review of randomized controlled trials of pharmacological therapy in osteoarthritis of the knee, with an emphasis on trial methodology. Semin Arthritis Rheum 1997; 26: 755–70. 36 Scott DL. Guidelines for the diagnosis, investigation and management of osteoarthritis of the hip and knee. J R Coll Phys 1993; 27: 391–96. 37 Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part I: osteoarthritis of the hip. Arthritis Rheum 1995; 38: 1535–40. 38 Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part II: osteoarthritis of the knee. Arthritis Rheum 1995; 38: 1541–46. 39. Lorig KR, Holman HR. Arthritis self management studies: a 12 year review. Health Educ Quart 1993; 20: 17-28. 40 Keefe FJ, Caldwell DS, Baucom D, et al. Spouse-assisted coping skills training in the management of osteoarthritic knee pain. Arthritis Care Res 1996; 9: 279–91. 41 Ettinger WH, Burns R, Messier SP, et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. JAMA 1997; 277: 25–31. 42 Felson DT, Ahange Y, Anthony JM, Naimark A, Anderson J.Weight loss reduces the risk for symptomatic knee osteoarthritis in women. Ann Intern Med 1992; 116: 535–39. 43 Martin K, Nicklas BJ, Bunyard LB, et al.Weight loss and walking improve symptoms of knee osteoarthritis [suppl]. Arthritis Rheum 1996; 39 (9): 225. 44 Henry D, Lim LL, Garcia Rodriquez LA, et al.Variability in risk of gastrointestinal complications with individual non-steroidal antiinflammatory drugs: results of a collaborative meta-analysis. BMJ 1996; 312: 1563–66. 45 Creamer P. Intra-articular steroids in osteoarthritis: do they work and if so how? Ann Rheum Dis 1997 (in press). 46 Spangler RS. Cyclooxygenase 1 and 2 in rheumatic disease: implications for nonsteroidal anti-inflammatory drug therapy. Semin Arthritis Rheum 1996; 26: 435–46. 47 Brune K. COX-2 selective NSAIDs: claims, hopes, and reality. Rheumatology 1997; 11: 3–4.
Further reading
Dequeker J, Boonen S, Aerssens J, Westhovens R. Inverse relationship osteoarthritis-osteoporosis: what is the evidence? What are the consequences? Br J Rheumatol 1996; 35: 813–88. Loughlin J, Irven C, Fergussen C, Sykes B. Sibling pair analysis shows no linkage of generalized osteoarthritis to the loci encoding type II collagen, cartilage link protein or cartilage matrix protein. Br J Rheumatol 1994; 33: 1103–06. Nakata K, Ono K, Miyazaki J, et al. Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha1(IX) collagen chains with a central deletion. Proc Natl Acad Sci USA 1993; 90: 2870–74.
General Moskowitz RW. Osteoarthritis. Rheum Dis Clin N A 1993; 19: 523–763. Pelletier JP. Osteoarthritis: challenges for the 21st century [suppl]. J Rheumatol 1995; 22 (43): 1–160. Hamerman D. Osteoarthritis: public health implications for an aging population. Baltimore: Johns Hopkins University Press, 1997.
Epidemiology EULAR Workshop. The epidemiology of osteoarthritis in the peripheral joints. Ann Rheum Dis 1996; 55: 651–94. Silman AJ, Hochberg MC. Epidemiology of the rheumatic diseases. Oxford: Oxford University Press, 1993: 257–88. Felson DT. The epidemiology of osteoarthritis: prevalence and risk factors. In: Kuettner K, Goldberg VM, eds. Osteoarthritic disorders. Rosemont: American Academy of Orthopaedic Surgeons, 1995: 13–24. Cicuttini FM. Spector TD. The genetics of osteoarthritis. J Clin Pathol 1996; 49: 617–19. Felson DT, Radin EL. What causes knee osteoarthritis: are different compartments susceptible to different risk factors? J Rheumatol 1994; 21: 181–83. Felson DT, Zhang Y, Hannan MT, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly. Arthritis Rheum 1997; 40: 728–33.
Pathogenesis Baldwin CT, Farrer LA, Adair R, Dharmavaram R, Jimenez S, Anderson L. Linkage of early onset osteoarthritis and chondrocalcinosis to human chromosome 8q. Am J Hum Genet 1995; 56: 692–97 Brandt K. Insights into the natural history of osteoarthritis provided by the cruciate-deficient dog. Ann N Y Acad Sci 1994; 732: 199–205. Kraus VB. Pathogenesis and treatment of osteoarthritis. Med Clin North Am 1997; 81: 85–112.
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Clinical features Dieppe PA, Cushnaghan J, Young P, Kirwan J. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by scintigraphy. Ann Rheum Dis 1993; 52: 557–63. Preidler KW, Resnick D. Imaging of osteoarthritis. Radiol Clin N A 1996; 34: 259–71. Scott DL, Houssien DA. Clinical and laboratory assessments in rheumatoid arthritis and osteoarthritis [suppl]. Br J Rheumatol 1996; 35 (3): 6–9. Jonsson H, Valtysdottir ST, Kjartansson O, Brekkan A. Hypermobility associated with osteoarthritis of the thumb base: a clinical and radiological subset of hand osteoarthritis. Ann Rheum Dis 1996; 55: 540–43. Wada M, Imura S, Baba H, Shimada S. Knee laxity in patients with osteoarthritis and rheumatoid arthritis. Br J Rheumatol 1996; 35: 560–63. Madsen OR, Bliddal H, Egsmose C, Sylvest J. Isometric and isokinetic quadriceps strength in gonarthrosis: interrelations between quadriceps strength, walking ability, radiology, subchondral bone density and pain. Clin Rheumatol 1996; 14: 308–14.
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Management Bellamy N, Bradley LA. Workshop on chronic pain, pain control, and patient outcomes in rheumatoid arthritis and osteoarthritis. Arthritis Rheum 1996; 39: 357–62. Brandt KD, Dieppe PA, eds. Management of pain in osteoarthritis: current approaches [suppl]. Drugs 1996; 52 (3): 1–62. Brandt KD. Modification by oral doxycycline administration of articular cartilage breakdown in osteoarthritis [suppl]. J Rheumatol 1995; 22 (43): 149–51 Brandt KD. Toward pharmacologic modification of joint damage in osteoarthritis [editorial]. Ann Intern Med 1995; 122: 874–75. Hochberg MC, Perlmutter DL, Hudson JI, Altman RD. Preferences in the managment of osteoarthritis of the hip and knee: results of a survey
of community based rheumatologists in the United States. Arthritis Care Res 1996; 9: 170–76. Lorig KR, Mazonson PD, Holman HR. Evidence suggesting that health education for self management in chronic arthritis has sustained health benefits while reducing health care costs. Arthritis Rheum 1993; 36: 439–46. Nguyen M, Revel M, Dougados M. Prolonged effects of 3 week therapy in a spa resort on lumbar spine, knee and hip osteoarthritis: follow-up after 6 months: a randomized controlled trial. Br J Rheumatol 1997; 36: 77–81. Schilke JM, Johnson GO, Housh TJ, O’Dell JR. Effects of muscle-strength training on the functional status of patients with osteoarthritis of the knee joint. Nurs Res 1996; 45: 68–72.
Issues in imaging
Evidence-based diagnostic radiology Adrian K Dixon The radiological community has a long track record of self-examination, starting well before evidence-based medicine came of age. It had to produce such evidence to prove the need for and win funds for its expensive gadgets. The assessment of new tests is easier than proving the value of well-established ones, and in scrutinising the evidence base for an imaging technique a balance must be struck between apparent (eg, diagnostic) benefit and real benefit to the patient. And even when there is a wealth of good evidence healthy debate continues. So radiology may be ahead of some other disciplines in considering the evidence for its daily practice. For example, where is the evidence for the routine clinical examination—and might the radiologist with a chest X-ray and abdominal ultrasound do better? Radiology is the most rapidly evolving specialty within medicine. In few other disciplines have doctors had to throw away so many old techniques and embrace the new. Witness the demise of lymphangiography1 and myelography2 against the spectacular growth of ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). And soon there will be further advances. Magnetic resonance cholangiopancreatography3,4 will replace diagnostic endoscopic studies of the pancreas, and ERCP (endoscopic retrograde choledochopancreatography) will become a treatmentonly technique. Spiral CT is likely to take over from nuclear medicine (ie, ventilation-perfusion scintigraphy) as the primary investigation for pulmonary embolism.5 And it is not difficult to predict the gradual eclipse of percutaneous diagnostic arteriography, given the rate of progress in ultrasound, CT, and MR angiography. These advances have been accompanied by a steady increase in the range of interventional radiology (discussed earlier in this Lancet series by Kenneth Thomson). Core biopsy6 after skilled mammographic and ultrasound investigations means that there are relatively few surprises for the breast surgeon; patients should live longer as a result of quicker and more accurate diagnosis. Most abdominal abscesses are now drained via radiologically guided catheters. Vascular radiologists offer a long list of effective intervention procedures, and the radiological/surgical vascular team of the future should be able to deal with most abdominal aortic aneurysms by Lancet 1997; 350: 509–12 Department of Radiology, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK (Prof A K Dixon FRCR)
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Figure 1: Balance for evaluation of diagnostic procedure Adapted from Kelsey Fry.10
stents rather than formal surgery. For such interventional procedures there are clear outcomes—eg, the patient is dead or alive, the graft is patent or occluded. The evidence for the benefits of such procedures is accruing. But where, some ask in these days of evidence-based medicine,7 is the justification for all the frenzied activity and expense in diagnostic (as opposed to interventional) radiology? Is there good work being done to prove that the patient’s lot is improved by high technology imaging?8,9 If the evidence is available, are the conclusions being put into practice?
Effectiveness of radiology Some years ago Kelsey Fry pointed out how difficult it is to evaluate new radiological techniques10 (figure 1). Fineberg’s hierarchical step-by-step method of evaluation11 (figure 2) has been widely adopted.12 Despite such helpful prompts, few radiologists have taken up the 509
Seminar
Osteoarthritis Paul Creamer, Marc C Hochberg Osteoarthritis is the most common form of arthritis. Osteoarthritis is a major cause of morbidity and disability as well as a burden on health-care resources, especially for the elderly. There have been advances in our understanding of this condition. No longer is osteoarthritis regarded as a simple consequence of ageing and cartilage degeneration; indeed, the former diagnostic label of degenerative joint disease is now recognised to be a misnomer. Rather, the pathological changes of osteoarthritis are seen as the result of active processes, many of which may be reparative rather than destructive in nature. In addition, osteoarthritis may not be a single disorder, but rather a group of overlapping distinct diseases. Risk factors, pathophysiology, clinical features and outcome vary from site to site, leading to the suggestion of osteoarthritic disorders as a more appropriate label.1 While aiming to be comprehensive, we will stress those areas in which most recent advances have been made.
Epidemiology A single definition of osteoarthritis remains elusive. A workshop held in 1995 proposed the following consensus definition: “Osteoarthritic diseases are a result of both mechanical and biologic events that destabilize the normal coupling of degradation and synthesis of articular cartilage chondrocytes and extracellular matrix, and subchondral bone. Although they may be initiated by multiple factors, including genetic, developmental, metabolic, and traumatic, osteoarthritis diseases involve all of the tissues of the diarthrodial joint. Ultimately, osteoarthritis diseases are manifested by morphologic, biochemical, molecular, and biomechanical changes of both cells and matrix which lead to a softening, fibrillation, ulceration, loss of articular carilage, sclerosis and eburnation of subchondral bone, osteophytes, and subchondral cysts. When clinically evident, osteoarthritis diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects.”1 A classification schema for primary and secondary osteoarthritis has been developed by the American College of Rheumatology (panel 1),2 as have classification criteria for osteoarthritis of the hand, hip, and knee.3 These latter criteria are most useful in clinical research, especially as Lancet 1997; 350: 503–09 Geriatric Research Education and Clinical Center, Maryland Veterans Affairs Health Care System, Baltimore (Prof M C Hochberg MD); and Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA (M C Hochberg, P Creamer MD) Correspondence to: Prof Marc C Hochberg, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland at Baltimore, MSTF Room 8–34, Baltimore, MD 21201, USA
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Panel 1: Classification of osteoarthritis2 ● Idiopathic Localised (eg, hands, feet, knees, hips, and other single sites) Generalised (three or more joint groups listed above) ● Secondary Post-traumatic Congenital or developmental diseases Localised (eg, hip dysplasia) Generalised (eg, chondrodysplasias, inherited metabolic diseases [ochronosis, haemochromatosis]) Calcium-deposition disease Other bone and joint disorders (eg, avascular necrosis, rheumatoid arthritis, Paget’s disease) ● Other diseases Endocrine diseases (eg, acromegaly, hyperparathyroidism) Neuropathical (Charcot’s) arthropathy Miscellaneous
inclusion criteria for clinical trials, rather than for case definition in epidemiological studies. Most epidemiological studies have defined cases of osteoarthritis based on the presence of typical radiographic features as originally described by Kellgren and Lawrence in 1957. The ability to compare epidemiological studies, especially those that estimate prevalence in different populations, is limited by variability in the accuracy of reading radiographs as well as other factors.4 In populations of white North Americans and Northern Europeans, about one-third of adults aged 25-74 years have features of radiographic osteoarthritis involving at least one peripheral joint group: the most common sites are the hands, followed by feet, knees, and hips. Much is known about the risk factors for radiographic osteoarthritis (panel 2, figure 1), and some studies suggest that they differ not only from joint to joint but also at different sites within the same joint (eg, patellofemoral vs tibiofemoral compartment of the knee joint).5 Furthermore, the principal risk factors for radiographic knee osteoarthritis (age, female sex, obesity, and joint trauma) are not the same as those reporting knee pain (psychosocial factors, general health status).6,7 Age is the strongest determinant of osteoarthritis with prevalence rates for all joints rising with increasing age. Incidence rates also rise with age but there is some evidence that this reaches a plateau in the seventh decade. The mechanism by which age predisposes to osteoarthritis is unclear. It is tempting to speculate that biochemical changes within aging cartilage render it more susceptible to damage and degradation but evidence to support this is lacking. Women are at higher risk of developing osteoarthritis than men, particularly after the menopause. While the biochemical effects of sex hormones on cartilage metabolism are complex and in-vitro and in-vivo animal studies have produced conflicting results; most epidemiological studies suggest that hormone-replacement therapy confers a protective effect on the development of 503
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Panel 2: Factors associated with osteoarthritis* ● Genetic factors Sex Inherited disorders of type II collagen (eg, Stickler’s syndrome) Mutations in the type II collagen gene (ie, COL2A1) Other inherited disorders of bones and joints Race/ethnicity ● Non-genetic host factors Increasing age Overweight Depletion of female sex hormones (eg, postmenopausal state) (?) Developmental and acquired bone and joint diseases Previous joint surgery (eg, meniscectomy) Race/ethnicity ● Environmental factors Occupations and physical demands of work Major trauma to joints Leisure and/or sports activities *Reproduced, with permission, from reference 9.
knee and hip osteoarthritis.8 The effects of sex hormones on cartilage may vary with menopausal status and stage of osteoarthritis. Obesity has been strongly linked to osteoarthritis of the knee and, to a lesser extent, the hip, in cross-sectional and prospective studies.9 Obesity may act by increasing mechanical stress in weight-bearing joints, but because women are more susceptible to the risks of obesity than men and because obesity may be a risk factor for osteoarthritis in the hand, systemic factors are also thought to be involved. Several studies in England and Sweden have focused on the role of occupation and sporting activity as risk factors for hip and knee osteoarthritis. Jobs involving kneeling, squatting, and climbing stairs are associated with higher rates of knee osteoarthritis, while jobs which require heavy lifting, including farming, are associated with higher rates
of hip osteoarthritis.9 Participation in sport has also been associated with an increased risk of lower-limb osteoarthritis. However, recreational physical activity, such as jogging, does not appear to increase the risk of osteoarthritis as long as the joints being subjected to repetitive stress are biomechanically normal. Although a hereditary component to osteoarthritis, particularly generalised osteoarthritis with Heberden’s nodes, has long been recognised, a recent study of female twin pairs showed significant heritability for radiographic features of osteoarthritis at the knee and hip.10 Although mutations in the gene for type II collagen (COL2A1) have been associated with early polyarticular osteoarthritis with mild chondrodysplasia, it is unlikely that there is a single gene for a structural component of cartilage that fully explains the genetic contribution to osteoarthritis.
Pathogenesis Osteoarthritis is generally seen as a disease of articular cartilage although it is clear that changes in subchondral bone are also important. Indeed, in idiopathic osteoarthritis, it remains unknown whether the initial abnormality occurs in the articular cartilage or the subchondral bone. Articular cartilage has two main functions: absorbing stress by deforming under mechanical load and providing a smooth load bearing surface to permit low-friction movement of the joint. The functional properties of cartilage result from its unique structure of chondrocytes embedded in a matrix of collagen and proteoglycan. The major structural protein is type II collagen, which consists of a triple helix of hydrophilic chains. The importance of type-II collagen is exemplified by the effect of mutations in the COL2A1 gene, but type-II collagen is also important in its ability to bind other matrix macromolecules, most notably types IX and XI collagen which, though present in small amounts, are critical for cartilage stability. The other major component of cartilage is proteoglycan, mainly
Figure 1: Aetiopathogenesis of osteoarthritis
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present as a large macromolecule called aggrecan. Aggrecan consists of a protein core to which many chondroitin and keratan-sulphate chains are attached, the core itself being attached to the hyaluronan skeleton via a link protein. Aggrecan is highly hydrophilic but also of low viscosity, ideally suited to its function of load dispersal. The gene for human aggrecan has been cloned and sequenced, and a preliminary study has shown an association between a polymorphism in this gene with polyarticular hand osteoarthritis in elderly men.11 Cartilage matrix turnover is a process of synthesis and degradation, which is balanced in healthy individuals. One view of osteoarthritis is as a failure to maintain this homeostatic balance, because of reduced formation or increased catabolism (figure 1). For example, matrix metalloproteinases—enzymes that catalyse both collagen and proteoglycan degradation including collagenase, gelatinase, and stromelysin—are found in increased concentrations in osteoarthritis cartilage, and their synthesis by chondrocytes can be stimulated by interleukin 1 (IL-1).12 Furthermore, blockage of these enzymes by doxycycline or chemically modified tetracyclines, at least in animal models, can reduce the severity of osteoarthritis lesions.13 Synthesis of cartilage components, on the other hand, appears to be dependent on a number of growth factors including insulin-like growth-factor 1 (IGF-1) and transforming growth-factor  (TGF). Although IGF-1 has been shown to reduce the development of osteoarthritis in animal models, evidence of a role for IGF-1 in human beings is conflicting: increased, reduced, and normal concentrations have been described in patients with osteoarthritis. The picture is equally confused with TGF. Much of this work has been done in vitro or in animal models and caution is needed when extrapolating to adult human beings. Subchondral bone changes are often seen on radiographs in patients with established osteoarthritis and increasingly these are viewed as an important cause of osteoarthritis rather than the sequelae of cartilage damage. It is known, for example, that the integrity of overlying cartilage depends on the mechanical properties of its bony bed. One model of osteoarthritis suggests that stiffening of subchondral bone, perhaps after repetitive microfractures, results in bone that is no longer effective as a shock absorber. Indirect evidence supporting a role for subchondral-bone turnover in osteoarthritis comes from: in-vivo studies of the guinea-pig model where changes in subchondral bone occur before cartilage changes are apparent;14 increased bone expression of matrix metalloproteinases and alkaline phosphatase in human hip osteoarthritis;15 and prospective studies in which bone changes as detected by scintigraphy have been shown to predict radiographic progression at both the hand and the knee.16 Evidence of the importance of bone also comes from the inverse association between osteoarthritis and diseases of low mineral density, most notably osteoporosis.17 Bone mineral density in patients with radiographic features of hip osteoarthritis is higher than in patients with normal radiographs, even after adjusting for body weight, not only in areas close to joints affected by osteoarthritis but also in sites away from these joints.18 The role of inflammation in the pathogenesis of osteoarthritis remains controversial. An inflammatory component may be present in osteoarthritis, at least in some patients at some phases of the disease. For example, there may be clear synovial hyperplasia and a dense Vol 350 • August 16, 1997
Panel 3: Symptoms and signs in patients with osteoarthritis ● Symptoms Joint pain Morning stiffness Gel phenomenon Buckling/instability Loss of function ● Signs Bony enlargement Limitation of range of motion Crepitus on motion Tenderness on pressure Pain on motion Joint effusion Malalignment, joint deformity, or both
mononuclear cell infiltrate, indistinguishable from that seen in rheumatoid arthritis.19 Such inflammation is focal, being most pronounced where the synovium is adjacent to cartilage.20 Expression of oncoproteins21 and nuclear factor (NF)B,22 an essential transcription factor for expression of various proinflammatory genes, have been found in osteoarthritis synovium. Nitric oxide synthase has also been found in chondrocytes from cartilage affected by osteoarthritis, and human articular chondrocytes, when stimulated by cytokines such as IL-1, release inflammatory mediators including nitric oxide.23 Nitric oxide may be directly toxic to articular cartilage; suggested mechanisms include down regulation of IL-1 receptor antagonist synthesis and induction of apoptosis of chondrocytes. Finally, systemic markers of inflammation such as Creactive protein are raised in many patients if a sensitive assay is used.24 The cause of inflammation in osteoarthritis remains unclear. Calcium pyrophosphate crystals can be shown to worsen the development of osteoarthritis in rabbit models,25 but their role and that of other crystals, such as basic calcium apatite, in human osteoarthritis is controversial.26 Once initiated, the release of wear particles may contribute to a cycle of inflammation resulting in further activation of synovium and release of cytokines. Although inflammation can be an important part of healing and repair, in the context of osteoarthritis it is generally regarded as harmful: in animal models, for example, the degree of inflammation correlates with the amount of cartilage loss. Inflammation may contribute to cartilage loss via production of inflammatory cytokines such as IL-1, which in turn result in release of matrix metalloproteinases, such as collagenases and stromelysin, as well as prostaglandins and plasminogen activators.27 Finally, in the dog model of osteoarthritis, the intraarticular administration of IL-1 receptor antagonist reduces the expression of collagenase and the subsequent development of osteoarthritis.28
Clinical features The clinical features of osteoarthritis are summarised in panel 3. Pain is the most important symptom which brings the patient to the doctor’s surgery; it is usually insidious in onset, mild-to-moderate in intensity, worsened by use of the involved joint, and improved with rest. Pain at rest or during the night are features of severe disease. Possible sources and causes of pain in patients with osteoarthritis include the synovial membrane, joint capsule, periarticular ligaments, periarticular muscle spasm, periosteum, and 505
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subchondral bone. Several observations strongly suggest as functional limitation and reduced quality of life may also that pain in patients with osteoarthritis is not simply the be included in trials.29 Systematic reviews of both nonresult of structural changes in the affected joint, but, rather, pharmacological33 and pharmacological therapy of lowerthe outcome of a complex interplay between structural limb osteoarthritis,34,35 as well as guidelines for the change, peripheral and central pain processing management of lower-limb osteoarthritis, have been mechanisms, and subjective differences in what constitutes published.36-38 A pyramid approach to the management of pain, which in turn are influenced by culture, sex, and patients with osteoarthritis is illustrated in figure 2. It is psychosocial factors.7 Indeed, although reporting of pain is important for the practitioner to recognise that the layers of significantly associated with the presence of radiographic the pyramid are added one to another in a stepwise fashion features of osteoarthritis in the general population, there is during the course of managing the individual patient (eg, a poor correlation between severity of pain and radiographic NSAIDs can be added on in lower dosages to a regimen features of osteoarthritis in patients. Nonetheless, valid and consisting of paracetamol and topical capsaicin, or intrareliable measures, including the Western Ontario McMaster articular corticosteroid injections can be given to patients Osteoarthritis Index, are now available to measure pain in already on paracetamol, NSAIDs, or both). clinical trials and outcome studies.29 Treatment should be individualised and based on the The clinical diagnosis of osteoarthritis is usually distribution and severity of joint involvement as well as the confirmed by the finding of typical radiographic changes presence of comorbid conditions. Education of patients, of osteoarthritis including marginal osteophytes, social support, and counselling are often beneficial. asymmetrical joint-space narrowing, subchondral bone Arthritis charities, such as the Arthritis and Rheumatism sclerosis, subchondral cyst formation and, in severe Council in the UK, the Arthritis Foundation in the cases, deformity of bone ends. Juxta-articular USA, and the Arthritis Society in Canada publish osteoporosis and marginal erosions, seen in brochures on education for patients and often patients with rheumatoid arthritis, are not a organise local self-help groups. Formal feature of osteoarthritis. Routine laboratory interventions include self-management tests, including complete blood count and programmes, such as the arthritis self-help chemistry panel, are usually normal. These and cognitive behavioural course39 laboratory tests should be obtained before approaches, designed to teach patients beginning therapy with a non-steroidal ways of coping with their pain.40 anti-inflammatory drug (NSAID) and Physical therapy has an important at annual intervals in patients on role in the management of long-term NSAID therapy.30 patients with osteoarthritis, The natural history of including instruction in muscle osteoarthritis is highly variable.16 strengthening exercises and Most studies have been done participation in aerobic in patients with knee osteoexercise programmes. arthritis, although some Quadriceps strengthening have included patients with exercises and aerobic Figure 2: Pyramid approach to the management of osteoarthritis hand and hip osteoarthritis.31 exercises have both been It is clear that, although shown to be effective in radiographic progression is reducing pain and usual, it is by no means inevitable, and a proportion of improving function in patients with knee osteoarthritis in patients with established osteoarthritis do not show further studies of up to 6 months.33 The technique for quadriceps progression on follow-up over several years. For example, strengthening is illustrated in figure 3. The patient is in a prospective observational study of 188 outpatients with instructed to lie on their back with one knee bent and the knee osteoarthritis, followed up for 1-5 years, 28% showed other leg straight with the ankle dorsiflexed to 90º. The no change in any radiographic feature.32 Some joints even quadriceps muscle of the straight leg is tightened and, appear to improve with apparent recovery of joint space, while keeping the knee straight, the leg is raised about 25though the degree to which this represents true cartilage 50 cm off the ground. The leg is held up for 10 s and then regrowth or simply an artefact of radiographic technique is lowered and the muscle relaxed. The exercise is repeated at not known. Similarly, pain, and less often function, can also least ten times alternating legs. improve. Changes on radiographs are often discordant with A multicentre study, by Ettinger and colleagues,41 that changes in pain; thus, radiographs may not be the most lasted 18 months showed that aerobic or resistive exercise appropriate outcome measure when designing intervention got better results than education for patients alone when studies in osteoarthritis. combined with standard pharmacological therapy in Certain features are now known to predict radiographic patients with knee osteoarthritis and mild disability. Data progession. In addition to abnormal bone scintigraphy, from well designed clinical trials support the routine these include obesity, presence of generalised osteoarthritis recommendation of exercise programmes in patients with with Heberden’s nodes, presence of chondrocalcinosis, and knee osteoarthritis. Occupational therapy may also be of raised serum concentrations of markers such as C-reactive value to patients to help them adapt to functional protein and hyaluronate.16 limitations by teaching them to do day-to-day activities. Weight reduction has been shown to reduce the risk of Management developing symptomatic knee osteoarthritis in an epidemiological study by Felson and colleagues,42 and to be Current treatment of osteoarthritis is purely to control associated with a reduction in both pain and impaired symptoms because as yet there are no disease-modifying function in overweight postmenopausal women with knee osteoarthritis drugs. The principal measure of treatment osteoarthritis.43 Diet counselling should also be a part of efficacy is traditionally pain, though other outcomes, such
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routine management for all overweight patients with moderate-to-severe lower-limb osteoarthritis in the past 20 osteoarthritis. years. With advances in prosthesis design, the rate of The main indication for drug therapy in osteoarthritis is revision due to loosening has fallen. pain. The drug of choice is currently paracetamol, which should be given at full dose for a reasonable time before Future other drugs are considered. A variable proportion of The understanding of the osteoarthritic disorders has patients will not respond to treatment and appear to derive increased over the past decade. The development of additional benefit from NSAIDs. It is reasonable to try selective cyclooxygenase-2 inhibitors may provide safer NSAIDs if non-pharmacological therapy and paracetamol NSAIDs which will improve the management of symptoms have failed to provide adequate symptom relief. There is no in patients with osteoarthritis.46,47 Studies of several novel clear evidence to suggest agents, including chemically superiority of one NSAID over modified tetracyclines and other another; however, indometacin metalloproteinase inhibitors, should not be used because of and IL-1 receptor antagonists greater comparative toxicity in have the potential to reverse the clinical trials.34,35 In addition, a structural or biochemical meta-analysis, by Henry and abnormalities of osteoarthritis found that Figure 3: Quadriceps strengthening exercise colleagues,44 are currently being investigated. piroxicam, ketoprofen, tolmetin In addition, autologous sodium, and azapropazone cartilage transplantation may be were associated with greater useful in patients with early risk of serious gastrointestinal complications such as disease and focal cartilage defects. Hopefully, these advances perforation, ulcers, and bleeds than other NSAIDs, will alter the prognosis and improve the quality of life for especially low-dose ibuprofen. General principles of patients with osteoarthritis in the coming century. NSAIDs used in osteoarthritis include: use of the PC is the recipient of a Travelling Postdoctoral Fellowship from the Arthritis minimum effective dose; avoidance of using more than one and Rheumatism Council, UK. NSAID simultaneously; assessment of benefit after about References 1 month (and cessation if no benefit is seen); and 1 Kuettner K, Goldberg VM. Osteoarthritic disorders. Rosemont: encouragement of intelligent non-compliance, such that American Academy of Orthopaedic Surgeons, 1995. the patient does not take medication if no pain is felt. 2 Altman R, Asch E, Bloch D, et al. Development of criteria for the Topical creams, either a NSAID or capsaicin, can be classification and reporting of osteoarthritis: classification of helpful as either monotherapy or when added to oral osteoarthritis of the knee. Arthritis Rheum 1986; 29: 1039–49. 3 Altman R. Classification of disease: osteoarthritis [suppl]. Semin Arthritis analgesics, especially if only one or more joints are involved. Rheum 1991; 20 (2): 40–47. In addition, topical creams give the patient a measure of 4 Spector TD, Hochberg MC. Methodological problems in the self control over their therapy which may itself be epidemiological study of osteoarthritis. Ann Rheum Dis 1994; 53: 43–46. beneficial. 5 Cooper C, McAlindon T, Snow S, et al. Mechanical and constitutional risk factors for symptomatic knee osteoarthritis: differences between Intra-articular steroids are widely used in osteoarthritis, medial tibiofemoral and patellofemoral disease. J Rheumatol particularly for the knee. There is some evidence to support 1994; 21: 307–13. their efficacy, but only for 1–3 weeks; triamcinolone 6 Davis M, Ettinger W, Neuhaus J, Barclay J, Degal M. Correlates of knee 45 hexacetonide is the most efficacious preparation. This pain among US adults with and without radiographic knee osteoarthritis. J Rheumatol 1992; 19: 1943–49. short efficacy is not reflected in clinical practice in which 7 Creamer P, Hochberg MC.Why does osteoarthritis of the knee hurt— some patients seem to have a sustained response to intrasometimes? Br J Rheumatol 1997; 37: 726–28. articular steroid. Efforts to identify predictors of response 8 Nevitt MC, Felson DT. Sex hormones and the risk of osteoarthritis in have proved largely unsuccessful. women: epidemiological evidence. Ann Rheum Dis 1996; 55: 673–76. 9 Hochberg MC, Lethbridge-Cejku M. Epidemiologic considerations in Intra-articular hyaluronic acid has also been shown to be the primary prevention of osteoarthritis. In: Hamerman D, ed. effective in patients with knee osteoarthritis; this therapy Osteoarthritis: public health implications for an aging population. requires weekly injections for 3–5 weeks and is more Baltimore: Johns Hopkins University Press, 1997: 169–86. efficacious than a single injection of intra-articular steroids. 10 Spector TD, Cicuttini F, Baker J, Loughlin J, Hart D. Genetic influences on osteoarthritis in women: a twin study. BMJ 1996; 312: 940–44. Patients whose pain is not adequately controlled by the 11 Horton W, Balakir R, Precht P, et al. Association between an aggrecan above measures may benefit from the judicious use of polymorphic allele and bilateral hand osteoarthritis in elderly white men: narcotic analgesics; however, controlled studies of these data from the Baltimore Longitudinal Study of Aging [suppl]. Arthritis Rheum 1996; 39 (9): 167. agents in patients with osteoarthritis are lacking and one 12 Woessner J Jr.The family of matrix metalloproteinases. Ann N Y Acad Sci must be concerned with the potential for long-term abuse. 1994; 732: 11–21. Tidal lavage with saline is effective in some patients with 13 Ryan ME, Greenwald RA, Golub LM. Potential of tetracyclines to knee osteoarthritis that has not responded to standard modify cartilage breakdown in osteoarthritis. Curr Opin Rheumatol 1996; 8: 238–47. medical therapy and is particularly useful in those for 14 Watson PJ, Hall LD, Malcolm A,Tyler JA. Degenerative joint disease in whom surgery is not recommended or refused. This can be the guinea pig: use of magnetic resonance imaging to monitor done with a needle arthroscope or even a sterile disposable progression of bone pathology. Arthritis Rheum 1996; 39: 1327–37. 14-gauge cannula, thereby avoiding the need for operating 15 Mansell JP,Tarlton JF, Bailey AJ. Biochemical evidence for altered subchondral bone collagen metabolism in osteoarthritis of the hip. theatre and general anaesthesia. The mechanism of action Br J Rheumatol 1997; 36: 16–19. of lavage is unknown; removal of wear particles and debris, 16 Hochberg MC. Prognosis of osteoarthritis. Ann Rheum Dis 1996; and removal of inflammatory mediators have all been 55: 685–88. suggested. 17 Star V, Hochberg MC. Osteoporosis in patients with rheumatic diseases. Rheum Dis Clin North Am 1994; 20: 561–76. Total joint replacement is an excellent treatment for 18 Nevitt MC, Lane NE, Scott JC, et al. Radiographic osteoarthritis of the osteoarthritis and has been responsible for a dramatic hip and bone mineral density: the Study of Osteoporotic Fractures improvement in the quality of life of individuals with Research Group. Arthritis Rheum 1995; 38: 907–16.
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THE LANCET 19 Haraoui B, Pelletier JP, Cloutier JM, Faure MP, Martel-Pelletier J. Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis. Arthritis Rheum 1991; 34: 153–63. 20 Lindblad S, Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum 1987; 30: 1081–88. 21 Roivainen A, Soderstrom KO, Pirila L, et al. Oncoprotein expression in human synovial tissue: an immunohistochemical study of different types of arthritis. Br J Rheumatol 1996; 35: 933–42. 22 Marok R,Winyard PG, Coumbe A, et al. Activation of the transcription factor nuclear factor-B in human inflamed synovial tissue. Arthritis Rheum 1996; 39: 583–91. 23 Amin AR, DiCesare PE,Vyas P, et al.The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase. J Exp Med 1995; 182: 2097–102. 24 Spector TD, Hart DJ, Nandra D, et al. Low level increases in serum Creactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 1997; 40: 723–27. 25 Fam AG, Morava-Protzner I, Purcell C,Young BD, Bunting PS, Lewis AJ. Acceleration of experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis. Arthritis Rheum 1995; 38: 201–10. 26 Schumacher HR Jr. Synovial inflammation, crystals, and osteoarthritis [suppl]. J Rheumatol 1995; 20 (43): 101–03. 27 Belcher C, Fawthrop F, Bunning R, Doherty M. Plasminogen activators and their inhibitors in synovial fluids from normal, osteoarthritis, and rheumatoid arthritis knees. Ann Rheum Dis 1996; 55: 230–36. 28 Caron JP, Fernandes JC, Martel-Pelletier J, et al. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis: suppression of collagenase-1 expression. Arthritis Rheum 1996; 39: 1535-44. 29 Bellamy N, Kirwan J, Boers M, et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip and hand OA: consensus development at OMERACT III. J Rheumatol 1977; 24: 799–802. 30 American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum 1996; 39: 723–31. 31 Dieppe PA, Cushnaghan J, Shepstone L.The Bristol “OA500” study: progression of osteoarthrits (OA) over 3 years and the relationship between clinical and radiographic features at the knee joint. Osteoarthritis Cartilage 1997; 5: 87–97. 32 Ledingham J, Regan M, Jones A, Doherty M. Factors affecting radiographic progression of knee osteoarthritis. Ann Rheum Dis 1995; 54: 53–8.
33 Puett DW, Griffin MR. Published trials of nonmedicinal and noninvasive therapies for hip and knee osteoarthritis. Ann Intern Med 1994; 121: 133–40. 34 Towheed TE, Hochberg MC. A systematic review of randomized controlled trials of pharmacologic therapy in osteoarthritis of the hip. J Rheumatol 1997; 24: 549–57. 35 Towheed TE, Hochberg MC. A systematic review of randomized controlled trials of pharmacological therapy in osteoarthritis of the knee, with an emphasis on trial methodology. Semin Arthritis Rheum 1997; 26: 755–70. 36 Scott DL. Guidelines for the diagnosis, investigation and management of osteoarthritis of the hip and knee. J R Coll Phys 1993; 27: 391–96. 37 Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part I: osteoarthritis of the hip. Arthritis Rheum 1995; 38: 1535–40. 38 Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part II: osteoarthritis of the knee. Arthritis Rheum 1995; 38: 1541–46. 39. Lorig KR, Holman HR. Arthritis self management studies: a 12 year review. Health Educ Quart 1993; 20: 17-28. 40 Keefe FJ, Caldwell DS, Baucom D, et al. Spouse-assisted coping skills training in the management of osteoarthritic knee pain. Arthritis Care Res 1996; 9: 279–91. 41 Ettinger WH, Burns R, Messier SP, et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. JAMA 1997; 277: 25–31. 42 Felson DT, Ahange Y, Anthony JM, Naimark A, Anderson J.Weight loss reduces the risk for symptomatic knee osteoarthritis in women. Ann Intern Med 1992; 116: 535–39. 43 Martin K, Nicklas BJ, Bunyard LB, et al.Weight loss and walking improve symptoms of knee osteoarthritis [suppl]. Arthritis Rheum 1996; 39 (9): 225. 44 Henry D, Lim LL, Garcia Rodriquez LA, et al.Variability in risk of gastrointestinal complications with individual non-steroidal antiinflammatory drugs: results of a collaborative meta-analysis. BMJ 1996; 312: 1563–66. 45 Creamer P. Intra-articular steroids in osteoarthritis: do they work and if so how? Ann Rheum Dis 1997 (in press). 46 Spangler RS. Cyclooxygenase 1 and 2 in rheumatic disease: implications for nonsteroidal anti-inflammatory drug therapy. Semin Arthritis Rheum 1996; 26: 435–46. 47 Brune K. COX-2 selective NSAIDs: claims, hopes, and reality. Rheumatology 1997; 11: 3–4.
Further reading
Dequeker J, Boonen S, Aerssens J, Westhovens R. Inverse relationship osteoarthritis-osteoporosis: what is the evidence? What are the consequences? Br J Rheumatol 1996; 35: 813–88. Loughlin J, Irven C, Fergussen C, Sykes B. Sibling pair analysis shows no linkage of generalized osteoarthritis to the loci encoding type II collagen, cartilage link protein or cartilage matrix protein. Br J Rheumatol 1994; 33: 1103–06. Nakata K, Ono K, Miyazaki J, et al. Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha1(IX) collagen chains with a central deletion. Proc Natl Acad Sci USA 1993; 90: 2870–74.
General Moskowitz RW. Osteoarthritis. Rheum Dis Clin N A 1993; 19: 523–763. Pelletier JP. Osteoarthritis: challenges for the 21st century [suppl]. J Rheumatol 1995; 22 (43): 1–160. Hamerman D. Osteoarthritis: public health implications for an aging population. Baltimore: Johns Hopkins University Press, 1997.
Epidemiology EULAR Workshop. The epidemiology of osteoarthritis in the peripheral joints. Ann Rheum Dis 1996; 55: 651–94. Silman AJ, Hochberg MC. Epidemiology of the rheumatic diseases. Oxford: Oxford University Press, 1993: 257–88. Felson DT. The epidemiology of osteoarthritis: prevalence and risk factors. In: Kuettner K, Goldberg VM, eds. Osteoarthritic disorders. Rosemont: American Academy of Orthopaedic Surgeons, 1995: 13–24. Cicuttini FM. Spector TD. The genetics of osteoarthritis. J Clin Pathol 1996; 49: 617–19. Felson DT, Radin EL. What causes knee osteoarthritis: are different compartments susceptible to different risk factors? J Rheumatol 1994; 21: 181–83. Felson DT, Zhang Y, Hannan MT, et al. Risk factors for incident radiographic knee osteoarthritis in the elderly. Arthritis Rheum 1997; 40: 728–33.
Pathogenesis Baldwin CT, Farrer LA, Adair R, Dharmavaram R, Jimenez S, Anderson L. Linkage of early onset osteoarthritis and chondrocalcinosis to human chromosome 8q. Am J Hum Genet 1995; 56: 692–97 Brandt K. Insights into the natural history of osteoarthritis provided by the cruciate-deficient dog. Ann N Y Acad Sci 1994; 732: 199–205. Kraus VB. Pathogenesis and treatment of osteoarthritis. Med Clin North Am 1997; 81: 85–112.
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Clinical features Dieppe PA, Cushnaghan J, Young P, Kirwan J. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by scintigraphy. Ann Rheum Dis 1993; 52: 557–63. Preidler KW, Resnick D. Imaging of osteoarthritis. Radiol Clin N A 1996; 34: 259–71. Scott DL, Houssien DA. Clinical and laboratory assessments in rheumatoid arthritis and osteoarthritis [suppl]. Br J Rheumatol 1996; 35 (3): 6–9. Jonsson H, Valtysdottir ST, Kjartansson O, Brekkan A. Hypermobility associated with osteoarthritis of the thumb base: a clinical and radiological subset of hand osteoarthritis. Ann Rheum Dis 1996; 55: 540–43. Wada M, Imura S, Baba H, Shimada S. Knee laxity in patients with osteoarthritis and rheumatoid arthritis. Br J Rheumatol 1996; 35: 560–63. Madsen OR, Bliddal H, Egsmose C, Sylvest J. Isometric and isokinetic quadriceps strength in gonarthrosis: interrelations between quadriceps strength, walking ability, radiology, subchondral bone density and pain. Clin Rheumatol 1996; 14: 308–14.
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Management Bellamy N, Bradley LA. Workshop on chronic pain, pain control, and patient outcomes in rheumatoid arthritis and osteoarthritis. Arthritis Rheum 1996; 39: 357–62. Brandt KD, Dieppe PA, eds. Management of pain in osteoarthritis: current approaches [suppl]. Drugs 1996; 52 (3): 1–62. Brandt KD. Modification by oral doxycycline administration of articular cartilage breakdown in osteoarthritis [suppl]. J Rheumatol 1995; 22 (43): 149–51 Brandt KD. Toward pharmacologic modification of joint damage in osteoarthritis [editorial]. Ann Intern Med 1995; 122: 874–75. Hochberg MC, Perlmutter DL, Hudson JI, Altman RD. Preferences in the managment of osteoarthritis of the hip and knee: results of a survey
of community based rheumatologists in the United States. Arthritis Care Res 1996; 9: 170–76. Lorig KR, Mazonson PD, Holman HR. Evidence suggesting that health education for self management in chronic arthritis has sustained health benefits while reducing health care costs. Arthritis Rheum 1993; 36: 439–46. Nguyen M, Revel M, Dougados M. Prolonged effects of 3 week therapy in a spa resort on lumbar spine, knee and hip osteoarthritis: follow-up after 6 months: a randomized controlled trial. Br J Rheumatol 1997; 36: 77–81. Schilke JM, Johnson GO, Housh TJ, O’Dell JR. Effects of muscle-strength training on the functional status of patients with osteoarthritis of the knee joint. Nurs Res 1996; 45: 68–72.
Issues in imaging
Evidence-based diagnostic radiology Adrian K Dixon The radiological community has a long track record of self-examination, starting well before evidence-based medicine came of age. It had to produce such evidence to prove the need for and win funds for its expensive gadgets. The assessment of new tests is easier than proving the value of well-established ones, and in scrutinising the evidence base for an imaging technique a balance must be struck between apparent (eg, diagnostic) benefit and real benefit to the patient. And even when there is a wealth of good evidence healthy debate continues. So radiology may be ahead of some other disciplines in considering the evidence for its daily practice. For example, where is the evidence for the routine clinical examination—and might the radiologist with a chest X-ray and abdominal ultrasound do better? Radiology is the most rapidly evolving specialty within medicine. In few other disciplines have doctors had to throw away so many old techniques and embrace the new. Witness the demise of lymphangiography1 and myelography2 against the spectacular growth of ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). And soon there will be further advances. Magnetic resonance cholangiopancreatography3,4 will replace diagnostic endoscopic studies of the pancreas, and ERCP (endoscopic retrograde choledochopancreatography) will become a treatmentonly technique. Spiral CT is likely to take over from nuclear medicine (ie, ventilation-perfusion scintigraphy) as the primary investigation for pulmonary embolism.5 And it is not difficult to predict the gradual eclipse of percutaneous diagnostic arteriography, given the rate of progress in ultrasound, CT, and MR angiography. These advances have been accompanied by a steady increase in the range of interventional radiology (discussed earlier in this Lancet series by Kenneth Thomson). Core biopsy6 after skilled mammographic and ultrasound investigations means that there are relatively few surprises for the breast surgeon; patients should live longer as a result of quicker and more accurate diagnosis. Most abdominal abscesses are now drained via radiologically guided catheters. Vascular radiologists offer a long list of effective intervention procedures, and the radiological/surgical vascular team of the future should be able to deal with most abdominal aortic aneurysms by Lancet 1997; 350: 509–12 Department of Radiology, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK (Prof A K Dixon FRCR)
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Figure 1: Balance for evaluation of diagnostic procedure Adapted from Kelsey Fry.10
stents rather than formal surgery. For such interventional procedures there are clear outcomes—eg, the patient is dead or alive, the graft is patent or occluded. The evidence for the benefits of such procedures is accruing. But where, some ask in these days of evidence-based medicine,7 is the justification for all the frenzied activity and expense in diagnostic (as opposed to interventional) radiology? Is there good work being done to prove that the patient’s lot is improved by high technology imaging?8,9 If the evidence is available, are the conclusions being put into practice?
Effectiveness of radiology Some years ago Kelsey Fry pointed out how difficult it is to evaluate new radiological techniques10 (figure 1). Fineberg’s hierarchical step-by-step method of evaluation11 (figure 2) has been widely adopted.12 Despite such helpful prompts, few radiologists have taken up the 509