What is Osteoarthritis (OA)?
Osteoarthritis can be viewed as the clinical and pathological outcome of a range of disorders that result in structural and functional failure of synovial joints with loss and erosion of articular cartilage, subchondral bone alterations, meniscal degeneration, a limited synovial inflammatory response, and bone and cartilage overgrowth (osteophytes) (1). It occurs when the delicate balance between the breakdown and repair of joint tissues becomes unbalanced (2). This progressive joint failure may cause pain and disability (3), although many persons with structural changes consistent with OA do not have symptoms (4). OA can occur in any synovial joint in the body, but is most common in the knees, hips, and hands. OA may affect a single joint or multiple joints.
What is the Impact of OA?
Most people over 60 years of age will have some form of OA and about half will have symptoms. It is becoming one of the most frequent diseases of elderly populations all over the world.
Typically osteoarthritis presents as joint pain. During a one year period, 25% of people over 55 years of age have a persistent episode of knee pain, of whom about one in six consult their doctor about it (5). Approximately 50% of these persons show evidence of knee osteoarthritis on x-ray. Symptomatic knee OA occurs in approximately 6% of persons aged 30 years or older and 12% of those 65 years or older. The risk of mobility disability (defined as needing help walking or climbing stairs) attributable to knee OA alone is greater than that due to any other medical condition in people aged 65 and over (3).
The burden to society, both in terms of personal suffering and the use of healthcare resources, of this highly prevalent condition is expected to increase with the increasing prevalence of obesity and the aging of the community. OA is currently ranked as the leading cause of disability among elders and by the year 2020, an estimated 60 million people will have arthritis. Knee pain from knee OA is a key symptom in the decision to seek medical care, and it often is the first reason for disability.
How is OA Diagnosed?
OA is a complex process in which mechanical factors play a central role and is characterized by changes in structure and function of the whole joint (6). A diagnosis is usually made by assessing many presenting clinical features on history and physical examination and can be confirmed by x-ray or other imaging methods.
The major risk factors for having OA include increasing age, female gender, obesity, joint injury and muscle weakness.
What is the Current Treatment of OA?
To date, there is no known cure for OA, and the goal of contemporary management of this disease remains control of pain and improvement in function and health-related quality of life with avoidance, if possible, of therapeutic toxicity. The current research agenda reflects a predilection for pharmacologic modification of pain, with inherent risk for toxicity, with little or no attention being paid to potentially modifiable risk factors for exacerbation of such pain.
The management of OA should be individualized so that it addresses the specific findings of the clinical examination. This is especially the case for findings of obesity, malalignment, and muscle weakness. Comprehensive management always includes a combination of treatment options that are directed towards the common goal of improving the patient's pain and tolerance for functional activity.
Treatment plans should never be defined rigidly according to the x-ray appearance of the joint (the structural alterations seen on x-ray are often poorly related to pain and functional limitation), but should instead remain flexible so that they can be altered according to the functional and symptomatic responses obtained.
Options for the conservative care of patients with OA are often overlooked (7). However, given the known toxicity and adverse event profiles of therapies such as NSAIDs, COX-2 inhibitors, and total joint replacement surgery, it is recommended that primary care for OA place far greater emphasis on non-pharmacologic treatments. Only when more conservative efforts fail to improve function should pharmaceuticals be offered. Surgery should be a last resort. There are guidelines available that describe the management of osteoarthritis that are based on evidence from trials and expert consensus (8-10).
What Does the Future Hold?
The current research agenda reflects a tendency for the use of pain medications with inherent risk for toxicity, with little or no attention being paid to potentially modifiable risk factors for exacerbation of such pain.
The use of pain medication for the management of symptoms is associated with many disadvantages. In particular, the frequent use of NSAIDs for elderly patients has been questioned because of their high risk for gastrointestinal (GI) and other toxicity. Identification of measures to prevent the development or exacerbation of pain is warranted.
This suggests that there is an opportunity to match the goals and interests of the research community with the interests and needs of its consumers. Pain is of great concern to patients with OA. Where research relates directly to patients and their experience of an illness, it is essential that their opinions are considered and avoidance of adverse side effects optimized.
For further information on osteoarthritis, please look at one of these references (11-13) or visit one of the following patient information websites:
Research Approaches at NEBH
- Developing and testing non-pharmacologic therapies (especially braces and shoe wear) for the management of knee osteoarthritis
- Natural history studies evaluating biomechanics, pain, and using MRI and biomarker measurements to improve understanding of predictors and progression of OA
- Tissue and molecular engineering studies to regenerate tissues in adults and to recapitulate key events in embryonic tissue formation and growth. These techniques have been used for a number of years for focal cartilage defects in persons without OA. The application of autologous chondrocyte transplantation and meniscal allograft surgery has been attempted in persons with OA with little success to date primarily because of lack of consideration of the altered mechanical environment and the continued activity of cytokines and chemokines. Careful thought and a staged approach to this activity could result in true biologic joint replacement.
- Translational approaches to improve our understanding of musculoskeletal disease etiopathogenesis through analysis of routinely discarded tissue from joint replacement surgeries. These analyses explore the histopathology and cell biology of diseased tissues in osteoarthritis, use gene expression to identify common transcripts that are differentially expressed in disease tissues versus uninvolved tissue, and identify new molecules that show a unique distribution to disease tissue and that have potential as molecular markers of this process using proteomics.
- Development of disease (structure) modifying therapies for osteoarthritis. OA is a clinical condition manifested by structural changes in many tissues. If structural modification is the intent of treatment, this should only be done mindful of attaining symptomatic improvement and not divorced from it. This is particularly important as there is a current predilection of focusing treatment targets on hyaline articular cartilage. Articular cartilage is both aneural and avascular. As such, cartilage is incapable of directly generating pain, inflammation, stiffness, or any of the symptoms that patients with OA typically describe. Given its relative unimportance to OA's symptomatic presentation, it is ironic that articular cartilage has received so much attention while other common symptom sources in the joint are ignored. Interventions that focus exclusively on nourishing, replenishing, or replacing articular cartilage have little chance of providing long-term symptomatic relief unless they also simultaneously relieve strain on other innervated structures. This is true whether the intervention is dietary, pharmacologic or surgical. A more logical approach is to assess the function of the entire joint organ and to target intervention to the reduction of pain and physical limitation on all moving parts. An important element in delineating the structural endpoints of choice for clinical trials is that they are associated with symptom change, or are at least, a surrogate for a clinically meaningful endpoint, as treatments which affect these structures are likely to alleviate pain. We are focusing on both endpoint (14) and clinical trial development with this perspective in mind.
Reference List
(1) Nuki G. Osteoarthritis: a problem of joint failure. [Review] [55 refs]. Zeitschrift fur Rheumatologie 1999; 58(3):142-147.
(2) Eyre DR. Collagens and cartilage matrix homeostasis. [Review] [37 refs]. Clinical Orthopaedics & Related Research 2004;(427 Suppl):S118-S122.
(3) Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW et al. The effects of specific medical conditions on the functional limitations of elders in the Framingham Study. American Journal of Public Health 1994; 84(3):351-358.
(4) Hannan MT, Felson DT, Pincus T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. Journal of Rheumatology 2000; 27(6):1513-1517.
(5) Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. [see comments.]. [Review] [45 refs]. Annals of the Rheumatic Diseases 2001; 60(2):91-97.
(6) Martin JA, Buckwalter JA. Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. [Review] [34 refs]. Iowa Orthopaedic Journal 2001; 21:1-7.
(7) Glazier RH, Dalby DM, Badley EM, Hawker GA, Bell MJ, Buchbinder R et al. Management of common musculoskeletal problems: a survey of Ontario primary care physicians.[see comment]. CMAJ Canadian Medical Association Journal 1998; 158(8):1037-1040.
(8) Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). [Review] [82 refs]. Annals of the Rheumatic Diseases 62(12):1145-55, 2003.
(9) Zhang W, Doherty M, Arden N, Bannwarth B, Bijlsma J, Gunther KP et al. EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).[see comment]. [Review] [113 refs]. Annals of the Rheumatic Diseases 2005; 64(5):669-681.
(10) Anonymous. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis & Rheumatism 2000; 43(9):1905-1915.
(11) Hunter DJ, Felson DT, Osteoarthritis. [Review] [20 refs]. BMJ 2006; 332(7542):639-642.
(12) Hunter DJ, In the clinic. Osteoarthritis. [Review] [115 refs]. Annals of Internal Medicine 2007; 147(3):ITC8.
(13) Eckstein F, Mosher T, Hunter D, Eckstein F, Mosher T, Hunter D. Imaging of knee osteoarthritis: data beyond the beauty. [Review] [100 refs]. Current Opinion in Rheumatology 2007; 19(5):435-443.
(14) Hunter D, Gale D, Grainger G, Lo G, Conaghan P. Development and reliability of a new scoring system for OA features on MRI of the knee. Osteoarthritis & Cartilage 13[Supplement A], P241. 2005.
Ref Type: Abstract