Osteoarthritis (OA) - Past, Present and Future

Cy Frank, M.D., FRCSC
2013 Macnab Lecturer, COA/CORS Annual Meeting

David Hart, PhD
Calgary, AB

The Past - What do we know about OA?
As described by many clinicians and researchers over the last several decades, Osteoarthritis (OA) is, by far, the most common type of arthritis. Whether described by the word 'Osteoarthrosis' that is preferred by some since the condition does not always involve inflammation, OA of literally every diarthrodial joint has been identified, including its most common locations in the knee, hip and spine. It can be unilateral or bilateral and many anatomic combinations of joint involvement have been seen. A recent review conducted by the COA's partners in the Arthritis Alliance of Canada (AAC), Canadian cohort data strongly suggests that the prevalence of OA will more than double in the decades ahead, and its future economic burden in Canada is predicted to grow exponentially1.


While considered a disease of the elderly for many years, the demographics of people with OA are changing. Many individuals are now developing OA at a young age, primarily due to the consequences of joint injuries. For example, even younger individuals who suffer an ACL tear and have the ligament reconstructed have a high incidence of OA by 15 years post-injury. In those with idiopathic OA, the incidence is similar in females and males prior to age 55, but the incidence during the post-menopausal years becomes closer to 2/1 in females/males2.

At a basic level, OA usually presents with progressive, often activity-related, joint pain, progressive loss of joint motion with related loss of function, and episodic swelling (early in the disease). Later in the disease, there is progressive and obvious osteophyte formation, joint deformity and loss of motion and a change in character of the pain to 'bone pain' as opposed to joint pain. Loading of the joint often causes more excruciating pain, with aching and night pain also becoming more common. All conservative measures become less and less effective in a subset of people for reasons that are as yet unclear.

As originally described by Mankin and his subsequent colleagues3, in many patients, these symptoms and signs do progress in concert with what have been thought to be predictable pathology in radiographic, gross and histologic assessments of the joint tissues. X-ray changes of osteophyte formation, joint space narrowing, subchondral sclerosis and cyst formation used to be the gold standard diagnostic changes, but more recently, articular cartilage abnormalities and loss on MRI's have become the non-invasive test of choice. Arthroscopic identification of cartilage softening, cracking and loss have provided another perspective on the pathology that accompanies joint symptoms. These changes, accompanied by those seen on MRI, have contributed to the misconception that OA is purely a disease of articular cartilage. This misconception stems from clear evidence that cartilage pathology is always involved in OA. The implication that treating only the cartilage pathology will cure the clinical syndrome has more recently been recognized to be false. As emphasized by Radin for decades4, either passive (alignment) or dynamic (neuromusclular/gait-related) biomechanical abnormalities of the joint can not only result in cartilage damage, but they must be corrected as a priority in allowing any restoration of joint structure and function.

The Present - How do we diagnose and treat OA now?
- As noted above, within the past two decades, there have been a number of advances in OA diagnosis and care. In terms of the diagnosis, MRI has allowed earlier detection of joint pathology, including the interesting identification of OA associated inflammatory marrow lesions within the bone5. Further, MRI has shown some changes in virtually every other tissue in and around the joint at different stages of OA. This has resulted in progressive recognition of the concept that OA is not just a disease of articular cartilage. In fact, OA may actually begin with changes or damage to other joint tissues (bone, synovium, ligaments, tendons, muscles and perhaps nerves). It is now recognized therefore that the 'treatment for OA' will thus likely target different tissues in different situations.

Non-surgical Care Options - Clinical care options have expanded, with more recognition of the importance of weight loss, neuromuscular training, control of joint loading (using orthotics, braces, therapy and various strengthening strategies), and different strategies for controlling joint pain and inflammation. In addition to oral anti-inflammatories and analgesics (Tylenol and NSAIDS), steroid injections and viscosupplementation are current clinical standards. Intravenous injections of 'biologicals' that block inflammatory pathways and have clearly changed natural histories of inflammatory arthritis are under current investigation, but thus far, they have not consistently improved OA. Injections of 'stem cells'6 and (PRP) platelet-rich plasma7 are, among things, under investigation for their potential to inhibit pain and inflammation, perhaps via some regenerative means. As of 2013, claims of regenerative capacity of these, or any joint resurfacing option, remain to be confirmed.

Surgical Options - As shown by Kirkley and colleagues8, arthroscopy has no role in treating OA per se. Arthroscopy is reserved for mechanical abnormalities and damage to other intra-articular or peri-articular structures that may be causing symptoms or may be causing painful impingements (menisci, labrum, bone abnormalities). Selective arthroscopic micro-fracture for more advanced disease is being investigated for its potential to delay the need for partial or full joint replacement. Various modifications of joint realignment and/or joint resurfacing are currently being evaluated for forms of OA that are diagnosed to be symptomatic because of what are thought to be locally correctable conditions.

Limitations of OA Treatment -Due to the low profile of this disease, patients with OA often suffer with it for years before seeking care and when they do seek care, it is currently highly variable. Primary care providers don't always recognize OA as a treatable condition and care is thus often delayed. When recognized, there are a number of treatment options as noted above, but none of them are 'curative'. The biggest advance in OA in recent years has been the clear recognition that not all OA is 'the same". Treatments are variably effective in subsets of patents for reasons that are not clear. Drug therapy is variably effective at inhibiting signs and symptoms, but it has been generally recognized that they are likely not preventing disease progression in most people. As noted above, arthroscopy definitely does not prevent disease progression. Perhaps due to expectations being too high, joint replacement for OA is also now recognized to not be quite as effective as originally thought, with a number of patients still having unexpected post-replacement issues. In an attempt to make expectations meet reality, patient selection for arthroplasty is currently a major area of research interest9.

Predisposing Causes and OA Pathogenesis - Genetic predisposition to OA is under intense investigation at the present time, with some gene associations reported10. Until these biological factors are better defined, only gross classification systems for OA are currently possible. While most were previously lumped into only one type of OA (idiopathic), at the present time this idiopathic group is shrinking and there are now at least two better recognized categories of OA. The first type is excessive biomechanical loading (that includes 'injury-induced') and the second is systemic/inflammatory OA (resulting from metabolic abnormalities that are often related to, or present as, overt obesity). The biomechanical causes of OA are now recognized to be associated with dynamic neuromuscular abnormalities (eg. adductor moment increases at the knee), while the latter type is related to what is now recognized as a 'metabolic syndrome' - or some predisposition to a systemic inflammation of many body organs at the same time (not just joints). The reason(s) for such a syndrome are currently under intense investigation as systemic treatments may help multiple organs, including the joints.

OA is a Complex Chronic Disease - As of 2013, it is recognized that not all OA is the same, as not all OA pain is the same. OA is not a simple degenerative disease of one or two tissues. It is a complex multisystem disease in many people. It is now known to interact with other chronic diseases (diabetes, cardiovascular disease, etc) or conditions (e.g. obesity, metabolic syndromes), and recognition of these multisystem patients do have implications to outcomes, and thus should have implications to treatment options. Further, there are a subset of patients who develop a chronic nociceptive pain with central and/or peripheral pain sensitization that don't respond to the usual treatments11. There are, in fact, a number of predictors of failed OA pain treatment, including: psychosocial factors, the burden (number) of painful joints, and pain intensity.

Current OA Research - OA research is currently expanding internationally with an annual meeting and a dedicated society called OARSI12. All four pillars of OA research are growing, with a number of promising new approaches emerging. Stem cells have been recognized in synovium and synovial fluid and may demonstrate some ability for intrinsic repair if inappropriate inflammation can be turned off13. More personalized approaches to both biological and biomechanical therapies that target better classified subsets of OA patients are beginning to emerge.

The Future of OA Care and Research
Over the next decade, we expect major advances in OA diagnosis and care, with much more scientific, quantitative disease classification and more personalized, targeted care. Blood tests and synovial fluid analysis will be used in combination with biomechanical/kinematic assessments to identify more precise or personalized approaches to therapy. Recently, the potential for serum and synovial fluid biomarker analysis to identify those with OA have been reported by our colleagues14. Their validation will add to the ability to phenotype patients and potential patients earlier in the disease. Cell therapies will become more practical and repair will be enhanced by targeted biological therapies.

We also expect that there will be several recognized subtypes of OA that will be identified earlier by imaging, and by biological and mechanical testing and triaged into different therapeutic categories. Patients with the systemic 'inflammatory syndromes' who present with obesity and joint pain will likely receive systemic therapies earlier in their disease, hopefully decreasing their progressive joint damage and decreasing the need for joint replacements. Bone targeted therapies will be tested and will likely have some clinical impact on pain and disability. Rehabilitation methods will become more targeted and personalized. Patients with subtypes of pain syndromes will be identified earlier and triaged away from surgery, as will patients with unrealistic expectations of joint replacement.

From a surgical perspective, joint realignment and resurfacing or replacement will remain gold standards for advanced disease in appropriately triaged patients. Regenerative options for various joint tissues (blocking inhibition of endogenous repair or enhancing it by cellular and/or other biological means) will receive increasing research and clinical attention. It seems highly unlikely that any single 'magic bullet' for OA will be defined and that combined approaches will be required. At a minimum,  OA will finally begin to receive scientific attention as a complex chronic disease, some of which can potentially be prevented or at least be inhibited.


  1. http://www.arthritisalliance.ca/docs/media/201209171000_framework_EN_588.pdf
  2. J. Am. Acad. Orthop. Surg. 2012 Oct;20(10):668-9. Sex differences in osteoarthritis of the knee. Boyan BD, Tosi L, Coutts R, Enoka R, Hart DA, Nicolella DP, Berkley K, Sluka K, Kwoh K, O'Connor MI, Kohrt W.
  3. Instr Course Lect. 2005;54:465-80. Articular cartilage and osteoarthritis. Buckwalter JA, Mankin HJ, Grodzinsky AJ.
  4. J Rheumatol. 2005 Jun;32(6):1136-8. Who gets osteoarthritis and why? An update. Radin EL.
  5. Am J Orthop (Belle Mead NJ). 2012 Sep;41(9):413-7. Subchondral bone marrow lesions associated with knee osteoarthritis. Sharkey PF, Cohen SB, Leinberry CF, Parvizi J.
  6. Nat Rev Rheumatol. 2013 Jul 23. Mesenchymal stem cells in joint disease and repair. Barry F, Murphy M.
  7. Curr Opin Rheumatol. 2013 May;25(3):310-6. New treatments for osteoarthritis. Smelter E, Hochberg MC.
  8. N Engl J Med. 2008 Sep 11;359(11):1097-107. A randomized trial of arthroscopic surgery for osteoarthritis of the knee. Kirkley A, Birmingham TB, Litchfield RB, Giffin JR, Willits KR, Wong CJ, Feagan BG, Donner A, Griffin SH, D'Ascanio LM, Pope JE, Fowler PJ.
  9. Arthritis Rheum. 2013 May;65(5):1243-52. Which patients are most likely to benefit from total joint arthroplasty? Hawker GA, Badley EM, Borkhoff CM, Croxford R, Davis AM, Dunn S, Gignac MA, Jaglal SB, Kreder HJ, Sale JE.
  10. Ann Rheum Dis. 2013 Sep 4. doi: 10.1136/annrheumdis-2012-203114. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. Evangelou E, et al.
  11. Osteoarthritis Cartilage. 2013 Sep;21(9):1236-42. Neuropathic pain symptoms on the modified pain DETECT correlate with signs of central sensitization in knee osteoarthritis. Hochman JR, Davis AM, Elkayam J, Gagliese L, Hawker GA.
  12. http://www.oarsi.org
  13. Stem Cells. 2013 Jul 8. doi: 10.1002/stem.1477. Monocyte Chemotactic Protein-1 Inhibits Chondrogenesis of Synovial Mesenchymal Progenitor Cells: an In vitro Study. Harris Q, Seto J, O'Brien K, Lee PS, Kondo C, Heard BJ, Hart DA, Krawetz RJ.
  14. J Rheumatol. 2013 Aug;40(8):1379-87. doi: 10.3899/jrheum.121204. Intraarticular and systemic inflammatory profiles may identify patients with osteoarthritis. Heard BJ, Fritzler MJ, Wiley JP, McAllister J, Martin L, El-Gabalawy H, Hart DA, Frank CB, Krawetz R.

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