To understand which treatments are likely to be effective, it is important to understand the different mechanisms underlying osteoarthritis, says Dr David Samra
Jack is a 49-year old ex-footballer who now works as a plumber. He has had a few years of medial knee pain.
Recently, Jack noticed that swelling is becoming a problem and the pain is getting worse. He had an ACL reconstruction and medial meniscal repair when he was 19, but had a successful career in Australian Rules football until an injury when aged 32 required a partial medial meniscectomy.
He is overweight with central adiposity, and finds kneeling at work is becoming impossible.
You examine his knee and there is a moderate effusion with isolated medial joint line tenderness. He has an apparent varus knee alignment.
You suspect early medial compartment osteoarthritis.
Jack wants to get an MRI, as he has heard this is the “only way to know its arthritis for sure”.
He asks you whether he should see a surgeon for “another scope and clean up”. Jack really wants to keep working as a plumber, and would love to be able to keep running. He has heard there are lots of treatments that can fix him, including “stem cells”.
Osteoarthritis (OA) is a very common condition and every GP will have patients who want to know what they can do about it.
Over one in eight Australian adults are affected and it’s been flagged as one of the fastest growing causes of years lived with disability over the past 20 years. (1)
It has high direct and indirect costs to society. The less definable costs include the contribution to a sedentary lifestyle for many patients, which is an independent risk factor for mortality. (2)
In the wake of this fact, and that up to two-thirds of patients are diagnosed with OA before retirement age, (3) sport and exercise medicine finds importance as a public health specialty. The elitism of the earlier days of this specialty, with its focus on professional athletes, has given way to rewarding partnerships with more sedentary, metabolically challenged patients to restore function and quality of life.
DIAGNOSIS
Would you perform an MRI?
Patients such as Jack can be reliably diagnosed with knee OA on clinical grounds. There is a wide variety of presenting features, but usage-related joint pain in a patient aged over 45 without mechanical features or prolonged morning stiffness is OA until proven otherwise.
Considering his history, risk-factors and clinical presentation, the most likely diagnosis is osteoarthritis. He does not describe mechanical symptoms such as locking or concerning systemic features such as unexplained weight loss.
Plain weight-bearing X-rays can be performed to provide baseline information about the joint space, but are neither sensitive or specific for the diagnosis. The Rosenberg view is a PA film done in a slightly flexed position which allows visualisation of the more posterior weight-bearing portion of the joint space.
Multiplanar X-rays may be helpful in assessing whether the medial or lateral compartment is under more pressure, particularly when there is visible varus or valgus malalignment. Bow-legged (varus) patients have increased medial compartment stress, while knock-kneed (valgus) patients have increased lateral compartment stress. Further advanced imaging is usually unnecessary unless there are concerning systemic or mechanical features to raise suspicion for acute cruciate or meniscal injury, AVN or malignancy.
Clinical and functional scores are recommended to obtain a baseline measure with which to assess the effects of treatment, and determine the role and timing for escalation of treatment. Validated measures include the KOOS (Knee Oxsteoarthritis Outcome Score) and WOMAC (Western Ontario McMaster University Osteoarthritis Index) questionnaire. Functional tests, such as the “timed up and go”, or a timed 40-metre walk test, are usually undertaken with the physiotherapist or exercise physiologist.
What if it’s a meniscal tear?
While advanced imaging is not recommended for OA, in reality, Jack’s age and surgical history could justify an MRI if plain X-rays were normal. This would be to assess the ACL graft and meniscal lesion and to answer the question of whether there is isolated meniscal pathology causing his medial joint line pain. MRI is much more sensitive to identify early osteoarthritis, since once loss of joint space and bony changes appear on X-ray the condition is fairly advanced. Meniscal pathology as a part of the OA process is most commonly seen as horizontal tears in the older age group.
The high prevalence of these tears and the lack of effective surgical treatment4-6 means an MRI is low yield in the presence of a clear clinical diagnosis of OA.
A holistic approach and GP partnership
OA is a complex condition. It was initially also called “degenerative joint disease”, in reference to the progressive loss of articular cartilage. Then the emphasis changed; with the knowledge that there is more than “wear”-related cartilage loss involved, and that both inflammatory and degradative pathways are involved that affect the whole joint, including periarticular tissues. More recently, the medical community are coming around to the notion that osteoarthritis is commonly an issue of general health, as both a sign and consequence of poor metabolic health.
The traditional medical model of referral and escalation of treatment for OA involves increasing specialisation with pathways to rheumatologists and orthopods who focus on joint health. In contrast, the role of the GP in optimising overall health is crucial, and partnership with sport and exercise medicine physicians can be very powerful in getting patients physically active.
What are we trying to achieve?
To understand which treatments are likely to be effective for your patient, it is important to understand the different mechanisms underlying OA. The harsh reality is that there are no disease-modifying agents for OA, largely because the pathophysiology follows many complex pathways that are not fully understood. It is no longer true to tell patients that OA represents a simple “wear and tear” process, as part of normal ageing. It is true that ageing is a factor, but only part of the process involves joint degeneration from mechanical and traumatic cartilage wear. The arthritic process is also strongly driven by pro-inflammatory mediators that promote “matrix metalloproteases” (MMPs), enzymes that progressively and irreversibly degrade articular cartilage, and also the periarticular tissues including the menisci and ligaments. These MMPs are thought to represent a final common pathway to joint (and periarticular) damage, and inhibition of this process has proven difficult due to problems with toxicity and lack of clinical effectiveness.
Different “phenotypes” of OA are thought to exist, which potentially changes the way treatment is directed.
Inflammatory OA
Patients with OA that affects multiple joints, particularly the hands, hips and knees are said to have “nodal OA”, whereas patients who have one or up to a few joints with significant morning stiffness and fluctuating, variable pain are likely to have a more inflammatory phenotype. There is some suggestion that this fluctuating, inflammatory phenotype may involve crystal arthropathy, in particular calcium pyrophosphate deposition.
Trauma
Post-traumatic OA represents another common pathway to knee OA. Chondral injury may elicit an initial and sustained inflammatory response that is perpetuated by matrix debris in the joint. The bone marrow oedema that is seen on MRI following significant knee injury (such as ACL rupture), correlates with the development of OA. (8) Researchers have found that the injured subchondral bone releases cytokines and proteinases that leads to articular cartilage breakdown- raising the idea that the process of OA may start in the bone.
Metabolic OA
There is a relatively new phenotype; metabolic associated OA. This is well supported by human and epidemiological studies showing overlap with features of the metabolic syndrome (hyperinsulinaemia), beyond overweight and obesity alone. (9) It is known that visceral fat produces circulating adipokines and macrophages, which are powerful promoters of inflammation. (10) This certainly supports the role of diet and exercise in promoting insulin sensitivity and reduction of visceral adiposity.
As we age, all of these processes gain momentum. Cellular ageing results in reduced responsiveness to growth and repair factors, and reduced cell turnover. At the same time, matrix ageing (12) increases collagen cross-linking and brittleness of articular cartilage. This has overlap with the metabolic pathogenesis, implicating prolonged exposure of joints to hyperinsulinaemia or hyperglycaemia as we age in a metabolically challenged society.
Can we slow the progression?
It is important to realise that symptomatic progression is generally slow in OA. Not all patients are inevitably going to require joint replacement surgery. In fact, the symptoms of knee OA tend to be stable over several years, with sudden deterioration being rare. (13) Therefore, patients must learn to manage their symptoms, adapt their lifestyle and daily activities to their knees and maintain some form of physical activity to mitigate the harms of a sedentary lifestyle.
We are currently still uncertain as to how to prevent deterioration in OA. Firstly, there is no universal pathophysiological problem that can be targeted because multiple different pathways contribute to the disease. Also, there is a poor correlation between imaging findings of joint space loss (commonly used to grade severity) and the symptoms of OA. In fact, researchers refer to “radiological OA” (ROA) as a separate entity to clinical OA.
What is seen currently is that treatments that may assist in symptomatic management may have no bearing on radiographic progression of the condition, and vice versa. Despite many years of pre-clinical and clinical studies on a range of biological agents, there are no treatments that have a confirmed disease-modifying effect for OA.
SIRT-1 is a protein responsible for multiple wide-reaching downstream effects, via de-acetylation of multiple transcription factors that affect metabolism cell death and inflammation. It is seen to be inhibited in the metabolic syndrome (particularly in fatty liver disease). Ways of modulating SIRT-1 are being explored as a means of managing many of the health concerns of modern society- including OA. The good news is that SIRT-1 appears to be upregulated by the things we do to improve general health- exercise and diet (caloric restriction). (15-17) The future may hold therapeutic agents that are able to upregulate it (the so called “exercise in a pill” concept).
I wouldn’t hold my breath for this.
MANAGEMENT
The role of the sport and exercise physician
In the precious time we have with our OA patients, the recent Clinical Care Standards recommend the provision of:
• A thorough clinical assessment
• Education and self-help strategies
• Individualised, concrete tools for weight loss, exercise maintenance and pain control
• Regular monitoring and goal setting
The clinical pathways that were developed as a result of these standards, placed sport and exercise physicians alongside physiotherapists as “non-specialists” in knee OA management.. Accordingly, GPs, physiotherapists and sport and exercise physicians are team members on the forward line of OA management, particularly for earlier disease.
Escalation to rheumatologist and orthopaedic care is more appropriate when there is an indication for systemic medical therapy or surgery.
OA management justifies a long consult to invest the time into understanding what they need to do to manage the condition The evidence-based physician understands the limited role of knee surgery in all but the most advanced knee OA, and works closely with trusted physiotherapists. The burden of OA is enormous, and sport and exercise physicians are experts in key areas of exercise prescription, metabolic management and non-surgical orthopaedics; with the capacity to rationalise health care costs including unnecessary surgical consultation and intervention.
Education is the starting point
Control, or at least perceived control is critically important to patient care. To directly involve patients in the management of chronic conditions is really a skill of asking the right questions. Motivational interviewing helps establish goals, with questions such as:
• What do you want to be able to do on your knee?
• What exercise do you love? (sometimes probing into sports they once played can spark a conversation)
• What have you done to date to manage your knee?
• What else do you think would help you?
• How do you think that would help?
Since lifestyle modification is the cornerstone of OA management, unhelpful beliefs are important to identify early, because they may sabotage the effectiveness of management and the patient’s sense of satisfaction. It is known that comorbid depression and helplessness predicts worse symptoms and more rapid progression of knee OA. (7)
Exploring the patients communication and thinking styles can help us intervene. “Magical thinking” describes the mindset of patients who believe all their problems will be solved if they receive the one “curative treatment”– so that fixing their knee will solve all problems in their life. Similarly, patients who transfer all responsibility for their problem to you are exhibiting “passive thinking”, and are more likely to explore treatments that do not require their input.
In the context of a progressive condition like OA, patients should be compelled to set realistic goals, take on the information we provide them and make informed decisions that involve them at the centre of their care.
Cognitive behavioural therapy (CBT) is embedded in our management of OA. Most clinicians will educate and clarify misconceptions (cognitive restructuring), encourage and reward positive behaviours (positive reinforcement), and monitor a gradual progression (pacing and grading). Physiotherapists and exercise physiologists are particularly skilled in the provision of CBT via exercise prescription- placing emphasis on function rather than pain. Programs of exercise prescription and pain coping skills training (PCST) have been shown reduce pain and improve function in comparison to education alone.
Many patients are quick to look for a therapy they can take that will alleviate or cure their condition. I see many patients who come in for an injection (of some description) for their OA knees; what they leave with is a better sense of what they can do to manage their condition; including concrete tools for weight loss, exercise and pain control.
What is the most effective type of exercise?
The evidence suggests that general aerobic exercise is effective for pain management. Walking or cycling are straight forward and easy to prescribe. Experienced clinicians prefer cycling because intensity can be increased without impact or high peak loads. Tai chi and aquatic exercise are also excellent options.18 Patients should be encouraged to find exercise they enjoy and are likely to adhere to. They should build up to the recommended guidelines of 30 minutes, five days per week; to accumulate at least 150 minutes of moderate intensity exercise weekly.
Progressive resistance training involves both the hip girdle and upper thigh musculature. an exercise physiologist would be an ideal team member to involve in providing exercises for this.
Striking the right balance
Patients commonly ask us whether they can continue to play their sport. This is difficult to answer scientifically because there is limited and conflicting data on whether impact sports (running in particular), accelerates OA. For the development of knee OA, the best available evidence suggests that neuro-anatomically normal knees are actually protected with repetitive, low impact exercise such as recreational running. Risk of OA increases with repetitive high impact exercise (such as competitive running or sport, which may be due to increased injury risk). (19–22)
However, neuro-anatomically abnormal knees (whether there is OA, malalignment, pre-existing injury, meniscal pathology or neuropathy) appear to have increased risk of progression to OA even with repetitive, low-impact exercise such as recreational running. These patients are often very disappointed when they hear this information, especially that they should no longer run, but most patients intuitively understand the reasoning. All tissues in the body are dynamic and resilient, but once there is joint damage the repair process cannot keep up.
Patients need alternatives, and it helps to understand their interests and be creative in developing an exercise prescription plan together.
There is an art and science to managing knee OA. It is a chronic, slowly progressive condition that has no disease modifying agent and is strongly linked to poor metabolic health.
This means we need to arm patients with ways of monitoring their OA, and help them to be pro-active in the long-term process using education, exercise and diet as the core interventions. The use the wide range of adjunctive treatments should be based on accessibility, risks and evidence-base, offered with patient’s OA phenotype and goals in mind.
Dr David Samra is a senior specialist registrar in sports and exercise medicine, currently working with the Sydney Swans. He is also a trained physiotherapist.
References:
1. Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437–41.
2. Chau JY, Grunseit A, Midthjell K, Holmen J, Holmen TL, Bauman AE, et al. Sedentary behaviour and risk of mortality from all-causes and cardiometabolic diseases in adults: evidence from the HUNT3 population cohort. Br J Sports Med. 2013 May 9;bjsports – 2012–091974.
3. Losina E, Weinstein AM, Reichmann WM, Burbine SA, Solomon DH, Daigle ME, et al. Lifetime risk and age of diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res [Internet]. 2013 May;65(5). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886119/
4. Herrlin S, Hållander M, Wange P, Weidenhielm L, Werner S. Arthroscopic or conservative treatment of degenerative medial meniscal tears: a prospective randomised trial. Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2007 Apr;15(4):393–401.
5. Buchbinder R, Harris IA. Arthroscopy to treat osteoarthritis of the knee? Med J Aust. 2013 Jul 22;199(2):100.
6. Sihvonen R, Paavola M, Malmivaara A, Itälä A, Joukainen A, Nurmi H, et al. Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear. N Engl J Med. 2013 Dec 26;369(26):2515–24.
7. Creamer P, Lethbridge-Cejku M, Hochberg MC. Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures. J Rheumatol. 1999 Aug;26(8):1785–92.
8. Tanamas SK, Wluka AE, Pelletier J-P, Pelletier JM, Abram F, Berry PA, et al. Bone marrow lesions in people with knee osteoarthritis predict progression of disease and joint replacement: a longitudinal study. Rheumatol Oxf Engl. 2010 Dec;49(12):2413–9.
9. Sellam J, Berenbaum F. Is osteoarthritis a metabolic disease? Jt Bone Spine Rev Rhum. 2013 Dec;80(6):568–73.
10. de Boer TN, van Spil WE, Huisman AM, Polak AA, Bijlsma JWJ, Lafeber FPJG, et al. Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis Cartilage. 2012 Aug;20(8):846–53.
11. Zheng S, Xu J, Xu S, Zhang M, Huang S, He F, et al. Association between circulating adipokines, radiographic changes, and knee cartilage volume in patients with knee osteoarthritis. Scand J Rheumatol. 2016;45(3):224–9.
12. Courties A, Gualillo O, Berenbaum F, Sellam J. Metabolic stress-induced joint inflammation and osteoarthritis. Osteoarthritis Cartilage. 2015 Nov;23(11):1955–65.
13. Collins JE, Katz JN, Dervan EE, Losina E. Trajectories and Risk Profiles of Pain in Persons with Radiographic, Symptomatic Knee Osteoarthritis: Data from the Osteoarthritis Initiative. Osteoarthr Cartil OARS Osteoarthr Res Soc. 2014 May;22(5):622–30.
14. Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol. 2011 Jan;7(1):23–32.
15. Nassir F, Ibdah JA. Sirtuins and nonalcoholic fatty liver disease. World J Gastroenterol. 2016 Dec 14;22(46):10084–92.
16. Corbi G, Conti V, Scapagnini G, Filippelli A, Ferrara N. Role of sirtuins, calorie restriction and physical activity in aging. Front Biosci Elite Ed. 2012 Jan 1;4:768–78.
17. Brooks CL, Gu W. How does SIRT1 affect metabolism, senescence and cancer? Nat Rev Cancer. 2009 Feb;9(2):123–8.
18. Bartels EM, Juhl CB, Christensen R, Hagen KB, Danneskiold-Samsøe B, Dagfinrud H, et al. Aquatic exercise for the treatment of knee and hip osteoarthritis. In: Cochrane Database of Systematic Reviews [Internet]. John Wiley & Sons, Ltd; 2016 [cited 2016 Jun 22]. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005523.pub3/abstract
19. Baumgarten B. To Run or Not to Run: A Post-Meniscectomy Qualitative Risk Analysis Model for Osteoarthritis When Considering a Return to Recreational Running. J Man Manip Ther. 2007;15(1):E1–15.
20. Leech RD, Edwards KL, Batt ME. Does running protect against knee osteoarthritis? Or promote it? Assessing the current evidence. Br J Sports Med. 2015 Nov;49(21):1355–6.
21. Timmins KA, Leech RD, Batt ME, Edwards KL. Running and Knee Osteoarthritis: A Systematic Review and Meta-analysis. Am J Sports Med. 2017 May;45(6):1447–57.
22. Buckwalter JA. Osteoarthritis and articular cartilage use, disuse, and abuse: experimental studies. J Rheumatol Suppl. 1995 Feb;43:13–5.
