Continuing Education Activity
Knee osteoarthritis (OA), also known as degenerative joint disease of the knee, is typically the result of wear and tear and progressive loss of articular cartilage. It is most common in the elderly. Knee osteoarthritis can be divided into two types, primary and secondary. Primary osteoarthritis is articular degeneration without any apparent underlying reason. Secondary osteoarthritis is the consequence of either an abnormal concentration of force across the joint as with post-traumatic causes or abnormal articular cartilage, such as rheumatoid arthritis (RA). Osteoarthritis is typically a progressive disease that may eventually lead to disability. The intensity of the clinical symptoms may vary from each individual. However, they typically become more severe, more frequent, and more debilitating over time. The rate of progression also varies for each individual. Common clinical symptoms include knee pain that is gradual in onset and worse with activity, knee stiffness and swelling, pain after prolonged sitting or resting, and pain that worsens over time. Treatment for knee osteoarthritis begins with conservative methods and progresses to surgical treatment options when conservative treatment fails. While medications can help slow the progression of RA and other inflammatory conditions, no proven disease-modifying agents for the treatment of knee osteoarthritis currently exist. This activity highlights the role of the interprofessional team in caring for patients with this condition.
Objectives:
Identify the etiology of knee osteoarthritis.
Review the appropriate history, physical, and evaluation of knee osteoarthritis.
Outline the management options available for knee osteoarthritis.
Describe interprofessional team strategies for improving communication to advance medical care and improve outcomes for knee osteoarthritis.
Access free multiple choice questions on this topic.
Introduction
Knee osteoarthritis (OA), also known as degenerative joint disease, is typically the result of wear and tear and progressive loss of articular cartilage. It is most common in the elderly. Knee osteoarthritis can be divided into two types, primary and secondary. Primary osteoarthritis is articular degeneration without any apparent underlying reason. Secondary osteoarthritis is the consequence of either an abnormal concentration of force across the joint as with post-traumatic causes or abnormal articular cartilage, such as rheumatoid arthritis (RA).
Osteoarthritis is typically a progressive disease that may eventually lead to disability. The intensity of the clinical symptoms may vary for each individual. However, they typically become more severe, more frequent, and more debilitating over time. The rate of progression also varies for each individual. Common clinical symptoms include knee pain that is gradual in onset and worse with activity, knee stiffness and swelling, pain after prolonged sitting or resting, and pain that worsens over time. Treatment for knee osteoarthritis begins with conservative methods and progresses to surgical treatment options when conservative treatment fails. While medications can help slow the progression of RA and other inflammatory conditions, no proven disease-modifying agents for the treatment of knee osteoarthritis currently exist.[1][2][3]
Etiology
Knee osteoarthritis is classified as either primary or secondary, depending on its cause. Primary knee osteoarthritis is the result of articular cartilage degeneration without any known reason. This is typically thought of as degeneration due to age as well as wear and tear. Secondary knee osteoarthritis is the result of articular cartilage degeneration due to a known reason.[4][5]
Possible Causes of Secondary Knee OA
Risk Factors for Knee OA
Modifiable
Articular trauma
Occupation – prolonged standing and repetitive knee bending
Muscle weakness or imbalance
Weight
Health – metabolic syndrome
Non-modifiable
Epidemiology
Knee osteoarthritis is the most common type of arthritis diagnosed, and its prevalence will continue to increase as life expectancy and obesity rises. Depending on the source, roughly 13% of women and 10% of men 60 years and older have symptomatic knee osteoarthritis. Among those older than 70 years of age, the prevalence rises to as high as 40%. The prevalence of knee osteoarthritis in males is also lower than in females. Interestingly, not everyone who demonstrates radiographic findings of knee osteoarthritis will be symptomatic. One study found that only 15% of patients with radiographic findings of knee OA were symptomatic. Not factoring in age, the incidence of symptomatic knee osteoarthritis is roughly 240 cases per 100,000 people per year.[6][7]
Pathophysiology
Articular cartilage is composed primarily of type II collagen, proteoglycans, chondrocytes, and water. Healthy articular cartilage constantly maintains an equilibrium between each of the components so that any degradation of cartilage is matched by synthesis. Healthy articular cartilage is thus maintained. In the process of osteoarthritis, matrix metalloproteases (MMPs), or degradative enzymes, are overexpressed, disrupting the equilibrium and resulting in an overall loss of collagen and proteoglycans. In the early stages of osteoarthritis, chondrocytes secrete tissue inhibitors of MMPs (TIMPs) and attempt to increase the synthesis of proteoglycans to match the degradative process. However, this reparative process is not enough. The loss in equilibrium results in a decreased amount of proteoglycans despite increased synthesis, increased water content, the disorganized pattern of collagen, and ultimately loss of articular cartilage elasticity. Macroscopically these changes result in cracking and fissuring of the cartilage and ultimately erosion of the articular surface.[8]
Although knee osteoarthritis is closely correlated with aging, it is important to note that knee osteoarthritis is not simply a consequence of aging but rather its own disease. This is supported by the differences seen in cartilage with both osteoarthritis and aging. Furthermore, the enzymes responsible for cartilage degradation are expressed in higher amounts in knee osteoarthritis, whereas they are at normal levels in the normal aging cartilage.
Histopathology
Cartilage Changes in Aging
[9]
Water content – decreased
Collagen – same
Proteoglycan content – decreased
Proteoglycan synthesis – same
Chondrocyte size – increased
Chondrocyte number – decreased
Modulus of elasticity – increased
Cartilage Changes in OA
Water content – increased
Collagen – disorganized
Proteoglycan content – decreased
Proteoglycan synthesis – increased
Chondrocyte size – same
Chondrocyte number – same
Modulus of elasticity – decreased
Matrix Metalloproteases
Responsible for cartilage matrix degradation
Stromelysin
Plasmin
Aggrecanase-1 (ADAMTS-4)
Collagenase
Gelatinase
Tissue Inhibitors of MMPs
Control MMP activity preventing excess degradation
TIMP-1
TIMP-2
Alpha-2-macroglobulin
History and Physical
Patients typically present to their healthcare provider with the chief complaint of knee pain. Therefore, it is essential to obtain a detailed history of their symptoms. Pay careful attention to the history as knee pain can be referred from the lumbar spine or the hip joint. It is equally important to obtain a detailed medical and surgical history to identify any risk factors associated with secondary knee OA.
The history of the present illness should include the following:
Onset of symptoms
Specific location of pain
Duration of pain and symptoms
Characteristics of the pain
Alleviating and aggravating factors
Any radiation of pain
Specific timing of symptoms
Severity of symptoms
The patient's functional activity
Clinical Symptoms of Knee OA
Knee Pain
Typically of gradual onset
Worse with prolonged activity
Worse with repetitive bending or stairs
Worse with inactivity
Worsening over time
Better with rest
Better with ice or anti-inflammatory medication
Knee stiffness
Knee swelling
Decreased ambulatory capacity
Physical examination of the knee should begin with a visual inspection. With the patient standing, look for periarticular erythema and swelling, quadriceps muscle atrophy, and varus or valgus deformities. Observe gait for signs of pain or abnormal motion of the knee joint that can indicate ligamentous instability. Next, inspect the surrounding skin for the presence and location of any scars from previous surgical procedures, overlying evidence of trauma, or any soft tissue lesions.
Range of motion (ROM) testing is an essential aspect of the knee exam. Active and passive ROM with regard to flexion and extension should be assessed and documented.
Palpation along the bony and soft tissue structures is an essential part of any knee exam. The palpatory exam can be broken down into the medial, midline, and lateral structures of the knee.
Areas of Focus for the Medial Aspect of the Lnee
Vastus medialis obliquus
Superomedial pole patella
Medial facet of the patella
Origin of the medial collateral ligament (MCL)
Midsubstance of the MCL
Broad insertion of the MCL
Medial joint line
Medial meniscus
Pes anserine tendons and bursa
Areas of Focus for the Midline of the Knee
Quadricep tendon
Suprapatellar pouch
Superior pole patella
Patellar mobility
Prepatellar bursa
Patellar tendon
Tibial tubercle
Areas of Focus for the Lateral Aspect of the Knee
A thorough neurovascular exam should be performed and documented. It is important to assess the strength of the quadriceps and hamstring muscles as these often will become atrophied in the presence of knee pain. A sensory exam of the femoral, peroneal, and tibial nerve should be assessed as there may be concomitant neurogenic symptoms associated. Palpation of a popliteal, dorsalis pedis, and posterior tibial pulse is important as any abnormalities may raise the concern for vascular problems.
Other knee tests may be performed, depending on the clinical suspicion based on the history.
Special Knee Tests
Patella apprehension – patellar instability
J-sign – patellar maltracking
Patella compression/grind – chondromalacia or patellofemoral arthritis
Medial McMurray – a medial meniscus tear
Lateral McMurray – lateral meniscus tear
Thessaly test – a meniscus tear
Lachman – anterior cruciate ligament (ACL) injury
Anterior drawer – ACL injury
Pivot shift – ACL injury
Posterior drawer – posterior cruciate ligament (PCL) injury
Posterior sag – PCL injury
Quadriceps active test – PCL injury
Valgus stress test – MCL injury
Varus stress test – LCL injury
Evaluation
In addition to a thorough history and physical, radiographic imaging is required. The recommend views include standing anteroposterior (AP), standing lateral in extension, and a skyline view of the patella. A standing 45-degree posteroanterior (PA) view of the knee may be obtained, which gives a better assessment of the weight-bearing surface of the knee. Occasionally, long leg standing films will be obtained to view the degree of deformity and overall alignment of the lower extremity. It is important to understand that radiographs of the knee must be obtained with the patient standing. This gives an accurate representation of the joint space narrowing present. Often, films will be taken with the patient supine, which gives a false sense of joint space and alignment and should not be used to evaluate suspected knee OA.[10][11][12]
Radiographic Findings of OA
Joint space narrowing
Osteophyte formation
Subchondral sclerosis
Subchondral cysts
Treatment / Management
Treatment for knee osteoarthritis can be broken down into non-surgical and surgical management. Initial treatment begins with non-surgical modalities and moves to surgical treatment once the non-surgical methods are no longer effective. A wide range of non-surgical modalities is available for the treatment of knee osteoarthritis. These interventions do not alter the underlying disease process, but they may substantially diminish pain and disability.[9][13][12]
Non-Surgical Treatment Options
[10]
Patient education
Activity modification
Physical therapy
Weight loss
Knee bracing
Acetaminophen
Nonsteroidal anti-inflammatory drugs (NSAIDs)
COX-2 inhibitors
Glucosamine and chondroitin sulfate
Corticosteroid injections
Hyaluronic acid (HA)
The first-line treatment for all patients with symptomatic knee osteoarthritis includes patient education and physical therapy. A combination of supervised exercises and a home exercise program have been shown to have the best results. These benefits are lost after 6 months if the exercises are stopped. The American Academy of Orthopedic Surgeons (AAOS) recommends this treatment.
Weight loss is valuable in all stages of knee osteoarthritis. It is indicated in patients with symptomatic arthritis with a body mass index greater than 25. The best recommendation to achieve weight loss is diet control and low-impact aerobic exercise. There is moderate evidence for weight loss based on the AAOS guidelines.
Knee bracing in osteoarthritis includes unloader-type braces that shift the load away from the involved knee compartment. This may be useful in the setting where either the lateral or medial compartment of the knee is involved, such as in a valgus or varus deformity.
Drug therapy is also the first-line treatment for patients with symptomatic osteoarthritis. A wide variety of NSAIDs are available, and the choice should be based on physician preference, patient acceptability, and cost. The duration of treatment with NSAIDs should be based on effectiveness, adverse effects, and past medical history. There is strong evidence for NSAID use based on the AAOS guidelines.
Glucosamine and chondroitin sulfate are available as dietary supplements. They are structural components of articular cartilage, and the thought is that a supplement will aid in the health of articular cartilage. No strong evidence exists that these supplements are beneficial in knee OA; in fact, there is strong evidence against the use according to the AAOS guidelines. There are no major downsides to taking the supplement. If the patient understands the evidence behind these supplements and is willing to try the supplement, it is a relatively safe option. Any benefit gained from supplementation is likely due to a placebo effect.
Intra-articular corticosteroid injections may be useful for symptomatic knee osteoarthritis, especially where there is a considerable inflammatory component. The delivery of the corticosteroid directly into the knee may reduce local inflammation associated with osteoarthritis and minimize the systemic effects of the steroid.
Intra-articular hyaluronic acid injections (HA) injections are another injectable option for knee osteoarthritis. HA is a glycosaminoglycan found throughout the human body and is an important component of synovial fluid and articular cartilage. HA breaks down during the process of osteoarthritis and contributes to the loss of articular cartilage as well as stiffness and pain. Local delivery of HA into the joint acts as a lubricant and may help increase the natural production of HA in the joint. Depending on the brand of HA, it can either be produced from avian cells or bacterial cells in the laboratory and therefore must be used with caution in those with avian allergies. While this is a prevalent treatment option, it is not highly supported in the literature, and there is strong evidence against its use based on the AAOS guidelines.
Surgical Treatment Options
[13]
A high tibial osteotomy (HTO) may be indicated for unicompartmental knee osteoarthritis associated with malalignment. Typically an HTO is done for varus deformities where the medial compartment of the knee is worn and arthritic. The ideal patient for an HTO would be a young, active patient in whom arthroplasty would fail due to excessive component wear. An HTO preserves the actual knee joint, including the cruciate ligaments, and allows the patient to return to high-impact activities once healed. It does require additional healing time compared to an arthroplasty, is more prone to complications, depends on bone and fracture healing, is less reliable for pain relief, and ultimately does not replace cartilage that is already lost or repair any remaining cartilage. An osteotomy will delay the need for arthroplasty for up to 10 years.
Indications for HTO
Young (less than 50 years old), active patient
Healthy patient with good vascular status
Non-obese patients
Pain and disability interfering with daily life
Only one knee compartment is affected
A compliant patient who will be able to follow postoperative protocol
Contraindications for HTO
Inflammatory arthritis
Obese patients
Knee flexion contracture greater than 15 degrees
Knee flexion less than 90 degrees
If the procedure will need greater than 20 degrees of deformity correction
Patellofemoral arthritis
Ligamentous instability
A UKA also is indicated in unicompartmental knee osteoarthritis. It is an alternative to an HTO and a TKA. It is indicated for older patients, typically 60 years or older, and relatively thin patients, although, with newer surgical techniques, the indications are being pushed.
Indications for UKA
Contraindications for UKA
Inflammatory arthritis
ACL deficiency
Fixed varus deformity greater than 10 degrees
Fixed valgus deformity greater than 5 degrees
Arc of motion less than 90 degrees
Flexion contracture greater than 10 degrees
Arthritis in more than one compartment
Younger, higher activity patients or heavy laborers
Patellofemoral arthritis
A TKA is the surgical treatment option for patients failing conservative management and those with osteoarthritis in more than one compartment. It is regarded as a valuable intervention for patients who have severe daily pain along with radiographic evidence of knee osteoarthritis.
Indications for TKA
Contraindications for TKA
Absolute
Active or latent knee infection
Presence of active infection elsewhere in the body
Incompetent quadriceps muscle or extensor mechanism
Relative
Neuropathic arthropathy
Poor soft-tissue coverage
Morbid obesity
Noncompliance due to major psychiatric disorder or alcohol or drug abuse
Insufficient bone stock for reconstruction
Poor health or presence of comorbidities that make the patient an unsuitable candidate for major surgery and anesthesia
Patient’s poor motivation or unrealistic expectations
Severe peripheral vascular disease
Advantages of UKA vs. TKA
Faster rehabilitation and quicker recovery
Less blood loss
Less morbidity
Less expensive
Preservation of normal kinematics
Smaller incision
Less post-surgical pain and shorter hospital stay
Advantages of UKA vs. HTO
Faster rehabilitation and quicker recovery
Improved cosmesis
Higher initial success rate
Fewer short-term complications
Lasts longer
Easier to convert to TKA
Differential Diagnosis
Any potential cause of local or diffuse knee pain should be considered in the differential diagnosis of knee osteoarthritis.
Prognosis
Strong evidence shows that age, ethnicity, BMI, the number of co-morbidities, MRI-detected infrapatellar synovitis, joint effusion, and both radiographic and the baseline of OA severity are predictive for clinical progression of knee osteoarthritis.[14] The most severe cases will result in total knee arthroplasty.[15]
Complications
Complications associated with non-surgical treatment are largely associated with NSAID use.
Common Adverse Effects of NSAID Use
Common Adverse Effects of Intra-Articular Corticosteroid Injection
Common Adverse Effects of Intra-Articular HA Injection
Injection site pain
Muscle pain
Trouble walking
Fever
Chills
Headache
Complications Associated with HTO
Complications Associated with UKA
Complications Associated with TKA
Postoperative and Rehabilitation Care
Postoperative and rehabilitation care after a TKA is aimed at restoring the highest possible range of mobility in and full muscular control of the operated knee. Adequate rehabilitation is an important requirement for successful TKA.[9] The specific rehabilitation program following a TKA is somewhat controversial and varies from surgeon to surgeon. Bed mobility, transfer training, and bedside exercises begin the same day as surgery. Full weight-bearing, typically with a walker, under the supervision of a therapist, is also allowed. Active range of motion (ROM), terminal knee extensions, straight leg raises, and muscle strengthening exercises begin postoperative day one. Gait training and transfers continue as well. In general, the patient must demonstrate safe ambulation with an assistive walking device on flat ground and stairs, the ability to safely transfer from bed to seated and standing positions, and adequate pain control prior to being discharged from the hospital. Patients are typically discharged to home or a skilled nursing facility. This is based on individual needs in consultation with social work. Discharge to home is greatly preferred if possible.
The typical hospital stays for a TKA is 1 to 2 nights, depending on the patient. The first postoperative visit is at the two-week mark, where a wound check is performed, and surgical staples are removed if present. Outpatient physical therapy will begin at this time if not begun already. The patient increases their ambulation, independence in their activities of daily living, works on their ROM and works on their quadriceps strength. Patients can resume driving when they can operate the pedals safely and rapidly. This usually takes 4 to 6 weeks. Return to work usually takes 4 to 10 weeks, depending on the work obligations. Patient follow-up is routinely at 6 weeks, 3 months, and one year after surgery. Once strength, mobility, and balance are regained, patients can resume low-impact sporting activities. High-impact activities are discouraged.
Deterrence and Patient Education
Patient education centers around non-medication and medication-based approaches. Non-medication approaches include weight loss, orthoses/bracing to correct joint alignment, exercise and physical therapy, and support groups. Medication compliance needs to be emphasized; sometimes, patient compliance wanes as symptomatic control from the drug occurs. Patients need to understand the disease has no cure and the likely progression that can take place, particularly with non-compliance to the therapeutic recommendations.
Pearls and Other Issues
The best predictor of final postoperative ROM following TKA is preoperative ROM, and patients should be aware of this before TKA.
Enhancing Healthcare Team Outcomes
Knee osteoarthritis (OA) is best managed by an interprofessional team that consists of an orthopedic surgeon, rheumatologist, physical therapist, dietitian, pain specialist, internist, nursing staff, physical therapist, and pharmacist. The disorder has no cure, and thus attempts should be made to prevent the progression of the disorder. The patient should be referred to a dietitian for weight loss and physical therapy to regain joint function and muscle strength. Treatment for knee osteoarthritis begins with conservative methods and progresses to surgical treatment options when conservative treatment fails. The pharmacist should look at the patient's medications to ensure there are no interactions and that the dosing and indications are all correct. While medications can help slow the progression of RA and other inflammatory conditions, no proven disease-modifying agents for the treatment of knee osteoarthritis currently exist. [Level 2]
Employing interprofessional collaboration and information sharing regarding the patient's case will drive better outcomes and increase the chances of avoiding TKA. [Level 5]
References
- 1.
Springer BD. Management of the Bariatric Patient. What Are the Implications of Obesity and Total Joint Arthroplasty: The Orthopedic Surgeon's Perspective?
J Arthroplasty. 2019 Jul;34(7S):S30-S32. [
PubMed: 30638728]
- 2.
Elsiwy Y, Jovanovic I, Doma K, Hazratwala K, Letson H. Risk factors associated with cardiac complication after total joint arthroplasty of the hip and knee: a systematic review.
J Orthop Surg Res. 2019 Jan 11;14(1):15. [
PMC free article: PMC6330438] [
PubMed: 30635012]
- 3.
Lundgren-Nilsson Å, Dencker A, Palstam A, Person G, Horton MC, Escorpizo R, Küçükdeveci AA, Kutlay S, Elhan AH, Stucki G, Tennant A, Conaghan PG. Patient-reported outcome measures in osteoarthritis: a systematic search and review of their use and psychometric properties.
RMD Open. 2018;4(2):e000715. [
PMC free article: PMC6307597] [
PubMed: 30622735]
- 4.
Manlapaz DG, Sole G, Jayakaran P, Chapple CM. Risk Factors for Falls in Adults with Knee Osteoarthritis: A Systematic Review.
PM R. 2019 Jul;11(7):745-757. [
PubMed: 30609282]
- 5.
Hulshof CTJ, Colosio C, Daams JG, Ivanov ID, Prakash KC, Kuijer PPFM, Leppink N, Mandic-Rajcevic S, Masci F, van der Molen HF, Neupane S, Nygård CH, Oakman J, Pega F, Proper K, Prüss-Üstün AM, Ujita Y, Frings-Dresen MHW. WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to occupational ergonomic risk factors and of the effect of exposure to occupational ergonomic risk factors on osteoarthritis of hip or knee and selected other musculoskeletal diseases.
Environ Int. 2019 Apr;125:554-566. [
PMC free article: PMC7794864] [
PubMed: 30583853]
- 6.
Magnusson K, Turkiewicz A, Englund M. Nature vs nurture in knee osteoarthritis - the importance of age, sex and body mass index.
Osteoarthritis Cartilage. 2019 Apr;27(4):586-592. [
PubMed: 30634033]
- 7.
Li JS, Tsai TY, Clancy MM, Li G, Lewis CL, Felson DT. Weight loss changed gait kinematics in individuals with obesity and knee pain.
Gait Posture. 2019 Feb;68:461-465. [
PMC free article: PMC6599530] [
PubMed: 30611976]
- 8.
Kisand K, Tamm AE, Lintrop M, Tamm AO. New insights into the natural course of knee osteoarthritis: early regulation of cytokines and growth factors, with emphasis on sex-dependent angiogenesis and tissue remodeling. A pilot study.
Osteoarthritis Cartilage. 2018 Aug;26(8):1045-1054. [
PubMed: 29782915]
- 9.
Collins NJ, Hart HF, Mills KAG. Osteoarthritis year in review 2018: rehabilitation and outcomes.
Osteoarthritis Cartilage. 2019 Mar;27(3):378-391. [
PubMed: 30529739]
- 10.
Afzali T, Fangel MV, Vestergaard AS, Rathleff MS, Ehlers LH, Jensen MB. Cost-effectiveness of treatments for non-osteoarthritic knee pain conditions: A systematic review.
PLoS One. 2018;13(12):e0209240. [
PMC free article: PMC6300294] [
PubMed: 30566527]
- 11.
Alrushud AS, Rushton AB, Bhogal G, Pressdee F, Greig CA. Effect of a combined programme of dietary restriction and physical activity on the physical function and body composition of obese middle-aged and older adults with knee OA (DRPA): protocol for a feasibility study.
BMJ Open. 2018 Dec 14;8(12):e021051. [
PMC free article: PMC6303593] [
PubMed: 30552242]
- 12.
Martel-Pelletier J, Maheu E, Pelletier JP, Alekseeva L, Mkinsi O, Branco J, Monod P, Planta F, Reginster JY, Rannou F. A new decision tree for diagnosis of osteoarthritis in primary care: international consensus of experts.
Aging Clin Exp Res. 2019 Jan;31(1):19-30. [
PMC free article: PMC6514162] [
PubMed: 30539541]
- 13.
Aweid O, Haider Z, Saed A, Kalairajah Y. Treatment modalities for hip and knee osteoarthritis: A systematic review of safety.
J Orthop Surg (Hong Kong). 2018 May-Aug;26(3):2309499018808669. [
PubMed: 30415598]
- 14.
Bastick AN, Runhaar J, Belo JN, Bierma-Zeinstra SM. Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies.
Arthritis Res Ther. 2015 Jun 08;17(1):152. [
PMC free article: PMC4483213] [
PubMed: 26050740]
- 15.
Rivero-Santana A, Torrente-Jiménez RS, Perestelo-Pérez L, Torres-Castaño A, Ramos-García V, Bilbao A, Escobar A, Serrano-Aguilar P, Feijoo-Cid M. Effectiveness of a decision aid for patients with knee osteoarthritis: a randomized controlled trial.
Osteoarthritis Cartilage. 2021 Sep;29(9):1265-1274. [
PubMed: 34174455]
Disclosure: Hunter Hsu declares no relevant financial relationships with ineligible companies.
Disclosure: Ryan Siwiec declares no relevant financial relationships with ineligible companies.
