Knee Osteoarthritis

Author(s): Daniel C. Herman, MD, Ashley D. Zapf, MD, Heather K. Vincent, PhD, Kevin R. Vincent, MD, PhD

Originally published:10/06/2015

Last updated:10/06/2015



The disease pathology of knee osteoarthritis is characterized by degeneration of articular cartilage and associated subchondral bone.1 It is traditionally classified as a non-inflammatory arthritis, although inflammatory processes are present in certain aspects of the disease.


Primary Knee Osteoarthritis (OA) is thought to be caused by repetitive mechanical stress, which initiates and perpetuates the degenerative process.2 Secondary OA is initiated in the context of prior trauma, sepsis, or inflammatory conditions with resultant joint instability, incongruity of the articular surface, and/or altered cartilage metabolism and matrix composition.3

Epidemiology including risk factors and primary prevention

OA is the leading cause of musculoskeletal debility in the world.2 Approximately 19-28% of Americans over the age of 45 have some degree of knee OA.4

Multiple local and systemic risk factors have been identified. Advanced age is the risk factor most associated with OA, with incidence rates increasing significantly over age of 50.5 Other risk factors include female sex, hormonal status, obesity, osteoporosis, ethnicity, genetic predisposition, dietary intake, muscle weakness, altered biomechanics, joint laxity/deformity, occupational factors, certain competitive sports, and previous trauma.6

The evidence for effective primary prevention of knee OA is somewhat limited; however, risk may be reduced through weight loss, regular exercise, prevention and management of osteoporosis.7,8,9


Initiation and progression of knee OA is a consequence of one or more factors including loss of cartilage matrix, alteration of the macromolecular matrix or chondrocyte injury. The disease may also involve focal macroscopic chondral or subchondral injury. Cartilage swelling may initially occur secondary to increased chondrocyte activity in response to such injury. Over time and with repetitive injury, chondrocyte activity drops and the cartilage begins to lose structural integrity, resulting in progressive surface fibrillations and erosions. Resultant breakdown products stimulate synovial inflammation, immune cell activity and high levels of proinflammatory cytokines as the disease progresses. The role of inflammation in symptom and disease progression in knee OA is unclear, but evidence indicates these factors exacerbate cartilage erosion.10 This injury to the cartilage may become sufficient to expose the subchondral bone, resulting in sclerosis, cystic changes, and overall loss of subchondral bone integrity.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Knee OA is characterized by an insidious onset of pain and progressive limited range of motion. Symptoms worsen over time, typically in an intermittent fashion. Patients note symptoms with ambulation, transfers, and ascending stairs. Knee stiffness or “locking” secondary to the formation of loose bodies, degenerative meniscal tears, and osteophyte formation may occur.11 These can significantly increase pain severity, hinder activities of daily living, and reduce quality of life.

Specific secondary or associated conditions or complications

OA has been linked to deformities of the knee joint, most often a various deformity.12Secondary altered biomechanics during functional tasks may lead to the development of pes anserine and/or trochanteric bursitis. Knee OA has also been associated with greater prevalence and increased risk of developing frailty in the elderly.13 Knee OA may alter gait patterns, aberrantly loading the contralateral joint during ambulation which may result in secondary osteoarthritis in the opposite hip and knee. Associated health effects such as weight gain and reduced cardiovascular health may arise from decreased activity levels14,15.



The Classic Clinical Criteria to diagnose knee OA from the American College of Rheumatology16 (Sensitivity 95%, Specificity 69%), includes knee pain, and at least 3 of the following:

1. Greater than 50 years of age
2. Morning stiffness for less than 30 minutes
3. Crepitus on active motion of the knee
4. Bony tenderness near the knee joint line
5. Bony enlargement about the knee joint
6. No palpable warmth

Physical Exam

Inspection: Assess for joint hypertrophy, varus/valgus deformity, effusion, and skin changes.

Palpation: Tenderness to palpation may be present. This is most commonly present at the medial joint line, or patellofemoral articulation.   An effusion may be palpable at the suprapatellar bursa with associated ballotment of the patella.

Range of Motion (ROM): Active and passive ROM may induce pain. ROM may be limited in flexion early in the course of disease with limitations in extension typically occurring in later stages.

Strength: Manual muscle testing may be limited secondary to pain. Muscle atrophy and weakness may be seen over time secondary to avoidance of painful activities. This is typically seen initially and most prominently in the quadriceps but may also involve the hamstrings and hip musculature.17

Special Tests: Instability may be noted on valgus and/or varus stress testing.

Clinical Functional Assessment

Pain and stiffness from knee osteoarthritis may cause difficulty with functional weight-bearing activities, such as ambulation, stair climbing, and transitioning from sit to stand. The times to complete load-bearing activities such as walk tests, timed-up-and go tests, chair rise and stair climb are slower in people with osteoarthritis compared with people who do not. The Osteoarthritis Research Society International recommends the use of a set of five performance-based tests of physical function in people knee OA:

1. Thirty Second Chair-Stand Test
2. Forty Meter Fast-Paced Walk Test
3. A stair-climb test (e.g. Single Step-Down Test or Step-Up Test; no specific test recommendation)
4. Timed Up-and-Go Test
5. Six Minute Walk Test

A description of the tests, copies of scoring sheets, and clinimetric data may be found here.

Surveys have also been developed and validated for use in the assessment of OA severity and treatment outcomes. Examples include the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), which is a 24-item assessment of a patient’s pain, stiffness and physical function; and the Knee injury and Osteoarthritis Outcome Score (KOOS), which is an assessment of pain, symptoms, activities of daily living, sports/recreation, and knee-related quality of life using a 42-item questionnaire.

Laboratory Studies

When laboratory findings are added to the American College of Rheumatology’s Classic Clinical Criteria16 sensitivity and specificity for the diagnosis of OA are 92% and 75%, respectively, with at least 5 of the 9 features present.

Erythrocyte Sedimentation Rate <40 mm/hr

Rheumatoid Factor Titer <1:40

Synovial Fluid with clear color, normal viscosity, and white blood cell count <2000


Weight-bearing radiographs aid evaluation. Anterior-posterior, lateral, notch, and Merchant views are recommended. Radiographic findings include joint space narrowing, subchondral bony sclerosis, osteophytes, cysts, and loose bodies, varus/valgus alignment, and osteopenia

Kellgren-Lawrence Radiographic Grading Scale for OA1

Grade 0: No radiographic findings of OA
Grade 1: Minute osteophytes of doubtful clinical significance
Grade 2: Definite osteophytes with unimpaired joint space
Grade 3: Definite osteophytes with moderate joint space narrowing
Grade 4: Definite osteophytes with severe joint space narrowing and subchondral sclerosis

When radiographic evidence of osteophytes is added to the American College of Rheumatology’s Classic Clinical Criteria16, the criteria has a Sensitivity of 91% and Specificity 86% for diagnosis of knee OA.

Supplemental Assessment Tools

MRI may be considered for diagnostic purposes very early in the course of knee OA as pathology can be detected before radiographic or morphologic changes become apparent18. MRI may also be considered to help evaluate or rule-out other knee conditions which may be present in the differential for a given patient.

Ultrasound imaging may allow for assessment of knee OA features such as synovial pathology and may be considered by sufficiently skilled operators when radiographs are inconclusive; however, ultrasound is limited by its inability to assess deeper articular structures and the subchondral bone18.

Early Predictions of Outcomes

Predictors of disease progression include age, obesity, the presence of OA in other joints, and varus deformity of the knee.19 Radiographic features of disease, including Kellgren-Lawrence Scale severity, presence of chondrocalcinosis, and osteophyte score, are also predictive of progression19. Increased physical activity (of any intensity level) and increased quadriceps muscle strength is associated with decreased progression of disability in adults with OA of the knee.20,21


Aquatic exercise is a viable option for those patients experiencing significant pain with land-based exercise. Access to resistance exercise equipment and safe walking routes or treadmills can help patients remain strong and active17,21,22. Ground floor habitation or living in buildings with elevator access can help improve a patient access.

Social Role and Support System

It is important to determine if the patient’s stiffness, pain, or decreased range of motion is interfering with his or her ability for self-care. Having someone who can provide assistance (be it a family member or paid caregiver) can ultimately affect the patient’s outcomes in dealing with OA.

Therapists and care teams can provide psychosocial support to patients by helping them understand that OA pain is a symptom that can be managed. This is very important in helping individuals overcome the fear of movement due to OA pain; a reduction in fear may help patients fully engage in safe exercise even when some knee pain is present. This process can help patients improve muscle strength and reduce the pain severity.

Professional Issues



Available or Current Treatment Guidelines

Guidelines for the treatment of OA of the knee have been published by the American College of Rheumatology (link), the American Academy of Orthopedic Surgeons (link), and the Osteoarthritis Research Society International (link).22,23,24

While differences exist among these three sets of recommendations, there is a relatively good level of agreement in the following non-surgical treatments:


Low-impact land-based exercise
Aquatic exercise
Strength training and neuromuscular education
Education and self-management
Weight loss in obese patients

Conditionally recommended:

Topical NSAIDs
Intra-articular corticosteroid injections

Three items are of particular note. First, regarding use of NSAIDs: In patients >75 years of age, a topical NSAID is recommended as oral NSAIDs increase the risk of serious gastrointestinal adverse outcome, including bleeding, ulcer or perforation. Second, the use of intra-articular hyaluronic acid injections is notably absent from the above list despite its common use in clinical practice. Recommendations between the societies ranged from a strong “cannot recommend its use” by the AAOS, to “no recommendation regarding its use” by the ACR, to “uncertain” by the OARSI. Additional study is clearly needed to more firmly establish the efficacy of this treatment. Finally, several braces (e.g. off-loader braces), orthotics (e.g. medial and lateral wedges), and assistive devices (e.g. canes) have been used in the treatment of knee OA. These items received inconsistent levels of review among the three societies with differing levels of recommendation when discussed by more than one society.

At Different Disease Stages

Early management of OA should focus on deceasing pain level, increasing function, and attempting to slow the disease progression.   Physical therapy for low-impact land-based exercise, aquatic exercise, and strength training and neuromuscular education should be considered as the foundation of the treatment plan for any stage of OA. Strength training should focus on improving quadriceps hamstrings, calf, and hip muscle strength. Structured weight loss programs should be implemented in patients who are overweight or obese. Oral analgesics, intra-articular injection, therapeutic modalities, and bracing/orthotics are additional treatment options that should be considered within the context of an individual patient and their co-morbidities.

Hyaluronic acid injections are a possible treatment in patients who fail initial conservative measures, although current evidentiary support is uncertain as reflected in the different levels of recommendations of use by the ACR, AAOS, and OARSI.

Arthroscopic debridement should not be considered as a means of intervention in patients with a primary diagnosis of knee osteoarthritis as there are very high levels of evidence that do no support its use.25 However, younger non-obese patients with symptom duration of <6 months stemming from a primary diagnosis of meniscal tear, loose body, or other mechanical derangement with a concomitant diagnosis of incidental mild (Kellgren-Lawrence Scale Grade 1) osteoarthritis of the knee may benefit in the event of failure of conservative measures.26

In later stages of the disease, some patients may fail conservative management and require surgical intervention in the form of joint arthroplasty.

Coordination of Care

OA is multifaceted and may require the input from several health care professionals. Direct communication among the care team members (therapist, physician, and family) is important to understanding the patient’s progress and helping to achieve optimal outcomes. When treating an elderly patient, communication with the primary care provider can help address medical issues that may be a barrier to therapy or other treatments. Care may also be coordinated with the primary care provider to help an obese patient enroll in a structured weight-loss program and obtain the help of a nutritionist or a bariatric surgeon.

Patient and Family Education

It is important to educate patients and family members about modifiable risk factors for the development and progression of OA, so they may target specific risk factors and make appropriate lifestyle changes to reduce the disease risk and manage OA symptoms.

Measurement of Treatment Outcomes

Multiple survey-based and objective functional measures of mobility and function have been developed as previously described in the Clinical Functional Measures section.

Translation into Practice

The use of both objective functional (e.g. Thirty Second Chair-Stand Test, Forty Meter Fast-Paced Walk Test) and survey-based (e.g. WOMAC, KOOS) treatment outcome measures have use for both tracking clinical course and response to treatments as well as providing measures of patient outcomes for quality of care reporting.


Cutting Edge/Emerging and Unique Concepts and Practice

Additional studies may establish the efficacy of intra-articular hyaluronic acid injections. Regenerative medicine techniques include intra-articular injection of mesenchymal stem cells or platelet-rich plasma (PRP); early studies have shown PRP injections may be more effective at reducing pain than placebo and hyaluronic acid injections.27 Limited evidence indicates prolotherapy may be useful in improving knee pain, function, and stiffness compared to baseline.28


Gaps in the Evidence Based Knowledge

Additional research is needed in determining factors which help predict which subgroups of patients may benefit from specific interventions, and combined interventions such as bracing or hyaluronic acid injections and exercise.

The optimal exercise prescription for OA symptom management remains unclear.

Better knowledge regarding osteoarthritis prevention strategies and interventions which can alter the course of OA progression, particularly in the post-traumatic injury knee, is needed.

Research is needed to determine whether there are OA pain phenotypes that are better responders to specific interventions.


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28. Rabago D, Patterson JJ, Mundt M, Zgierska A, Fortney L, Grettie J, Kijowski R. Dextrose and morrhuate sodium injections (prolotherapy) for knee osteoarthritis: a prospective open-label trial. J Altern Complement Med. 2014 May; 20(5): 383-391.

Author Disclosure

Daniel C. Herman, MD
Nothing to Disclose

Ashley D. Zapf, MD
Nothing to Disclose

Heather K. Vincent, PhD
Nothing to Disclose

Kevin R. Vincent, MD, PhD
Nothing to Disclose

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