Elsevier

The Lancet

Volume 377, Issue 9783, 18–24 June 2011, Pages 2115-2126
The Lancet

Series
Osteoarthritis: an update with relevance for clinical practice

https://doi.org/10.1016/S0140-6736(11)60243-2Get rights and content

Summary

Osteoarthritis is thought to be the most prevalent chronic joint disease. The incidence of osteoarthritis is rising because of the ageing population and the epidemic of obesity. Pain and loss of function are the main clinical features that lead to treatment, including non-pharmacological, pharmacological, and surgical approaches. Clinicians recognise that the diagnosis of osteoarthritis is established late in the disease process, maybe too late to expect much help from disease-modifying drugs. Despite efforts over the past decades to develop markers of disease, still-imaging procedures and biochemical marker analyses need to be improved and possibly extended with more specific and sensitive methods to reliably describe disease processes, to diagnose the disease at an early stage, to classify patients according to their prognosis, and to follow the course of disease and treatment effectiveness. In the coming years, a better definition of osteoarthritis is expected by delineating different phenotypes of the disease. Treatment targeted more specifically at these phenotypes might lead to improved outcomes.

Introduction

The prevalence of osteoarthritis is dependent on the precise definition used and on the site of interest. The knee, hip, and hand are most affected by the disease (figure 1). Osteoarthritis becomes more common with age, and after age 50 years more women than men are affected. For example, the Rotterdam study1 of a population-based cohort of 3906 people 55 years or older reported that 67% of women and 55% of men had radiographic osteoarthritis of the hand. In people older than 80 years, 53% of women and 33% of men had radiographic osteoarthritis of the knee. The age-standardised and sex-standardised incidence of osteoarthritis of the hand is 100 per 100 000 person-years, for the hip is 88 per 100 000 person-years, and for the knee is 240 per 100 000 person-years.2

Osteoarthritis in general develops progressively over several years, although symptoms might remain stable for long periods within this period. The diagnosis of the disease relies on clinical and radiological features (panel).3 Nearly half of patients with radiological features of osteoarthritis have no symptoms and vice versa. Risk factors for occurrence and progression of osteoarthritis have been identified, and differ on the basis of the joints involved (table 1).3

In addition to the involvement of several joint tissues, osteoarthritis has long been mainly characterised by a failure of the repair process of damaged cartilage due to biomechanical and biochemical changes in the joint. Cartilage is non-vascularised, so this restricts the supply of nutrients and oxygen to the chondrocytes—the cells that are responsible for the maintenance of a very large amount of extracellular matrix. At an early stage, in an attempt to effect a repair, clusters of chondrocytes form in the damaged areas and the concentration of growth factors in the matrix rises.4, 5 This attempt subsequently fails and leads to an imbalance in favour of degradation. Increased synthesis of tissue-destructive proteinases (matrix metalloproteinases and agrecanases),6, 7 increased apoptotic death of chondrocytes, and inadequate synthesis of components of the extracellular matrix, lead to the formation of a matrix that is unable to withstand normal mechanical stresses. Consequently, the tissue enters a vicious cycle in which breakdown dominates synthesis of extracellular matrix. Since articular cartilage is aneural, these changes do not produce clinical signs unless innervated tissues become involved. This is one reason for the late diagnosis of osteoarthritis.

Although the pathophysiology of osteoarthritis has long been thought to be cartilage driven, recent evidence shows an additional and integrated role of bone and synovial tissue, and patchy chronic synovitis is evident in the disease.8 Synovial inflammation corresponds to clinical symptoms such as joint swelling and inflammatory pain, and it is thought to be secondary to cartilage debris and catabolic mediators entering the synovial cavity. Synovial macrophages produce catabolic and proinflammatory mediators and inflammation starts negatively affecting the balance of cartilage matrix degradation and repair.9 This process in turn amplifies synovial inflammation, creating a vicious cycle. Synovial inflammation happens in early as well as late phases of osteoarthritis and is seldom as severe as in rheumatoid arthritis, but it might add to the vicious cycle of progressive joint degeneration.

The main characteristics of osteoarthritis are changes in the subchondral bone. Osteophyte formation, bone remodelling, subchondral sclerosis, and attrition are crucial for radiological diagnosis. Several of these bone changes take place not only during the final stage of the disease, but also at the onset of the disease—possibly before cartilage degradation.10, 11 This finding led to the suggestion that subchondral bone could initiate cartilage damage.

Pain is the first and predominant symptom of osteoarthritis that causes patients to visit their family doctor. The pain experienced is intermittent, typically worst during and after weight-bearing activities. Inflammatory flares can happen during the course of the disease. Patients with osteoarthritis also experience stiffness: in the morning, after a period of inactivity, or particularly in the evening. This stiffness generally resolves in minutes, unlike the prolonged (usually >30 min) stiffness caused by rheumatoid arthritis.

Loss of movement and function is another reason patients visit their family doctor. Patients report symptoms that limit their day-to-day activities, such as stair climbing, walking, and doing household chores. Symptomatic osteoarthritis might be associated with depression and disturbed sleep, which additionally contribute to disability. The symptoms of osteoarthritis diminish the patients' quality of life.12

Physical examination is needed to confirm and characterise joint involvement, and to exclude pain and functional syndromes with other causes—eg, inflammatory arthritis.13 Joint enlargement results from joint effusion, bony swelling, or both. A synovial effusion might not only be identified during osteoarthritis flares, but also during chronic phases as a persistent feature. Restricted passive movement can be the first and sole physical sign of symptomatic disease. Bursitis, tendinitis, muscle spasm, and tissue response to, for instance, damaged meniscus can cause the same pain syndrome and must be carefully sought during examination. Crepitus, a sensation of crunching or crackling, is commonly felt on passive or active movement of a joint with osteoarthritis. Joint deformities relate to advanced disease with joint damage that involves cartilage, periarticular bone, synovium, articular capsule, ligaments, and muscles (figure 2). A joint can lock if loose bodies or fragments of cartilage (or meniscus) get into the joint space. Caution should be exercised to correctly attribute pain to the correct site—eg, patients with osteoarthritis of the hip might report knee pain because of referred pain or anserine bursitis. Additional neurological and spine examination is often needed.

Imaging investigations are seldom needed to confirm the diagnosis; they might be useful to establish the severity of joint damage and to monitor disease progression. However, some sites and clinical scenarios need imaging assessment (including MRI or scintigraphy) to exclude other diseases, including avascular osteonecrosis, Paget's disease, complex regional pain syndrome, inflammatory arthropathies, and stress fractures. Also, blood tests are not routinely needed in cases of uncomplicated chronic pain arising from clearly defined osteoarthritis. ESR and C-reactive protein are usually within the normal range. Some laboratory tests might be done to exclude other diseases, such as anti-cyclic citrullinated peptide antibodies for rheumatoid arthritis and uric acid for gout. Synovial fluid should be assessed if another arthropathy or septic arthritis is suspected. In patients with osteoarthritis, synovial fluid is sterile, without crystals, and a white-cell count of less than 1500 cells per μL.

Section snippets

Markers of tissue damage

Why there is little relation between clinical characteristics and structural tissue changes in osteoarthritis remains unclear.14, 15 Insensitivity of available monitoring methods for damage to joint tissue combined with slow progression of this damage might underlie the discrepancy. Assessment of structural changes is a challenge in studying the disease and improving treatment modalities.

Early and minimum tissue damage is difficult to assess in vivo. Biopsies for detailed histochemical and

Treatment

In early osteoarthritis, pain and stiffness dominate the other symptoms.73 Treatment should therefore focus on the reduction of pain and stiffness and on the maintenance and improvement of functional capacities. Furthermore, prevention of progression of joint damage and improvement of quality of life are long-term goals. There are three treatment modalities: non-pharmacological, pharmacological, and surgical. In many patients these modalities are combined, tailored to individual needs and risk

New developments

New discoveries about the pathophysiology of osteoarthritis prompt the division of the disease into distinguishable phenotypes. Delineating the different clinical and structural phenotypes of the disease will improve understanding—of disease in patients with pain, trauma, or obese-dominated clinical phenotypes (table 4 lists our attempt)—and will also allow specific targeted treatment in those in whom structural changes in either cartilage, bone, or synovial tissue dominate the disease.

Search strategy and selection criteria

The information in our paper is primarily based on PubMed searches with the terms “osteoarthritis” in combination with “cartilage”, “bone”, “synovitis”, “imaging”, “biomarker”, and “treatment”. We mainly included papers from the past 5 years, with the addition of highly regarded older papers. We also included some review articles and book chapters as comprehensive overviews, the details of which are beyond the scope of our report.

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