Knee Osteoarthritis

Description of knee osteoarthritis:[edit | edit source]

According to JAMA more than 10 million Americans are affected with knee osteoarthritis.[1]Most commonly affecting a population age 45 and greater this condition occurs as the cartilage in the knee wears away eventually causing bone on bone contact between joint surfaces. Most common complaints include joint swelling, joint stiffness, and pain. Knee osteoarthritis can be diagnosis via radiographs indicating boney cysts, narrowing joint space, and scelrosing of the bone.

Knee osteoarthritis is the occurrence of osteoarthritis(OA) in the knee joint. Osteoarthritis has many definitions, but Kuttner et al . defined it as follows: “Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, is a group of overlapping distinct diseases, which may have different etiologies but with similar biologic, morphologic, and clinical outcomes.”[2]

In other words osteoarthritis involves the degradation of joints, including articular cartilage and subchondral bone. But also ligaments, the capsule and the synovial membrane degenerate. This will eventually lead to pain and loss of function.[3]

Osteoarthritis is the most common disease of joints adults suffer from worldwide. The name ‘osteoarthritis’, a Greek word, can be divided in ‘osteo’, ‘arthro’ and ‘it is’. If we translate the word we become ‘of the bone’, ‘joint’ and ‘inflammation’.”[4] Thus, simply put, we can say that osteoarthritis is an inflammation of the bone and joint. Besides knee osteoarthritis, which is the most common, you also have hand and hip osteoarthritis.

[5]
[6]

Anatomy and Pathological Process:[edit | edit source]

The knee joint consists of both approximation of the proximal tibia and the distal end of the femur. The cartilage located on the ends of the femur and tibia contain an extra cellular matrix that contains type 2 protoglycans that function by drawing fluid into the joint causing increased shock absorption and proper joint nutrition.[7] There is some evidence to support that as the aging process occurs the type 2 collagen fibers decrease in size and therefore less fluid an nutrition gets into the joint surfaces eventually leading to decreased protection along boney surfaces.

Knee-OA1.png

The knee (art. genus) is a synovial joint, which consists of 3 articulations. The primary joint, art. tibiofemoral, is located between the convex femoral condyles and the concave tibial condyles.[8] There is also the art. patellofemoralis between the femur and the patella and the art. tibiofibularis located between the tibia and fibula. OA can only occur in the two primary articulations of the knee, namely the tibiofemoral and patellofemoral joint, because they have to sustain more motion than the art. tibiofibularis.[2]

“The pathogenesis of knee OA have been linked to biomechanical and biochemical changes in the cartilage of the knee joint.” (Kirstin Uth et al, 2014)[9] The cartilage ensures that the bone surfaces can move painless and with low friction to each other. In OA, the cartilage decreases in thickness and quality, it becomes thinner and softer, cracks may occur and it will eventually crumble off. Cartilage that has been damaged, cannot recover. Finally the cartilage will disappear. The bone surfaces can also be affected, the bone will expand and spurs (osteophytes) will develop.[10][11]

Not only the cartilage can be affected, there can also occur laxity of the ligaments and muscle atrophy. [12] [13]

Epidemiology /Etiology[edit | edit source]

Osteoarthritis is the most prevalent form of arthritis and occurs especially in the knee joint. It affects nearly 6% of all adults, but more women are affected than men.[3] “According to a number of published reports, anywhere from 6% to over 13% of men, but between 7% and 19% of women, over 45 years of age are affected, resulting in a 45% less risk of incidence in men (Coleman, et al).” [14]

Age is a determining factor in the development of OA. “As the population ages in demographic terms, the prevalence of OA is expected to rise (Coleman, et al).” [14] From the age of 40 there is an increased risk of OA. Approximately 50% of the 65+ population are affected by OA in the knee, but it can also affect young people. [14]

Age is not the only factor that plays a role in the evolution of OA. Other risk factors are[4]:

  • Obesity
  • Joint hypermobility or instability
  • Sport stress with high impact loading
  • Repetitive knee bending or heavy weight lifting
  • Specific occupations
  • Peripheral neuropathy
  • Injury to the joint
  • History of immobilisation
  • Family history

Characteristics/Clinical Presentation[edit | edit source]

Signs of knee osteoarthritis are pain at beginning of the movement, later on pain during movement and eventually permanent pain. These patients will also experience a loss of function like stiffness, decreased range of motion (ROM) and impairment in everyday activities. Other possible characteristics of knee OA are bony enlargement, crepitus, joint-line tenderness and elevated sensitivity to cold and/or damp.[4]

We can subdivide knee osteoarthritis in 5 stages:

  • Stage 0: This is the “normal” knee health, without any pain in the joint functions.
  • Stage 1: A person in this stage has very minor bone spur growth and is not experiencing any pain or discomfort.
  • Stage 2: This is the stage where people will experience symptoms for the first time. They will have pain after a long day of walking and will sense a greater stiffness in the joint. It is a mild stage of the condition, but X-rays will already reveal greater bone spur growth. The cartilage will likely remain at a healthy size.
  • Stage 3: Stage 3 is considered as a moderate osteoarthritis. People with this stage will experience a frequent pain during movement. The joint stiffness will also be more present, especially after sitting for long periods and in the morning. The cartilage between the bones shows obvious damage, and the space between the bones is getting smaller.
  • Stage 4: This is the most severe stage of osteoarthritis. The joint space between the bones will be dramatically reduced, the cartilage will almost be completely gone and the synovial fluid will be decreased. That is why people will experience lots of pain and discomfort during walking or moving the joint.[15]

Differential Diagnosis[edit | edit source]

The diagnosis can be established by clinical examination, and it can be confirmed by X-rays. The main characteristics are changes in the subchondral bone, joint space narrowing, subchondral sclerosis, subchondral cyst formation and osteophytes. In early stage of osteoarthritis, the results of the radiography can show a minimal unequal joint space narrowing. If it deteriorates you still find the same problems, but the patient experiences a lateral subluxation of the tibia as well. If it deteriorates more, the joint line will disappear completely. It is shown in the picture that the medial joint space is more narrow than the lateral joint line.[4]


Stages Knee OA.jpg[16]


Some differential diagnosis can be: bursitis, iliotibial band syndrome, ligamentous instability (medial and lateral collateral ligaments) and meniscal pathology, these are conditions in whereby the soft tissues of the knee are affected. But also other forms of arthritis can lead to differential diagnosis of the knee, think of gout and pseudogout, rheumatoid arthritis and septic arthritis.[17]

Diagnostic Procedures[edit | edit source]

[18]

Symptoms:[19]

Primary:

  • Pain
  • Stiffness, particularly in the morning
  • Sensitivity when kneeling or bending[15]
  • Decrease in the abilities of daily functioning
  • More commonly diagnosed[4]

Secondary:

  • Loss of mobility in the affected joint
  • Decrease in muscle power
  • Instability of the joint
  • Crepitations
  • This type of OA can be caused by obesity, trauma, inflammatory or genetically[4]

X-ray: The basic X-ray is used to research breakdown of cartilage, narrowing of joint space, forming of bone spurs and to exclude other causes of pain in the affected joint.

Arthrocentesis: This is a procedure which can be performed at the doctor’s office. A sterile needle is used to take samples of joint fluid which can then be examined for cartilage fragments, infection or gout.

Arthroscopy: is a surgical technique where a camera is inserted in the affected joint to obtain visual information about the damage caused to the joint by the osteoarthritis.

The European League Against Rheumatism developed diagnostic criteria for diagnosing knee osteoarthritis. The most important factors are shown in the following figure.[19]

File:Risc factors.jpg
EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis

Examination[edit | edit source]

If a patient is referred to you by a doctor, it is most likely he performed a medical examination. It is imperative to look at his/her findings when examinating the patient.

  • Inspection: Mind the position of the joints when in rest and how the patient moves. This can be accomplished by making the patient perform simulations of daily activities such as getting up from and down on a chair, stair climbing, etc.
  • Palpation: Mind: swelling, temperature differences, muscle tonus. Also be wary of possible bone spurs (osteocytes) that have formed on the edge of the joint. These osteocytes are a serious indication towards osteoarthritis.
  • Examination of basic functions: Testing of muscle power, coordination, mobility, balance and also stability of the joint. These factors can be tested by active test like standing on one leg and passive manual tests. When testing stability of the joint muscle strength and proprioception are of significant importance.

Medical Management[edit | edit source]

Medical PT.png[20]


The main goal of any therapy for patients with knee OA in most cases is to reduce pain and improve the physical functioning. The summary[20] as mentioned above is consisted of numerous treatments for osteoarthritis, divided into medical and physical therapy management.

Although pharmacological treatment is not proven to have outcomes that are of crucial importance and despite its controversy, medications are often recommended by doctors.[4] Medicines that are primarily used by patients with knee OA, with or without co-morbidities[20]:

  Acetaminophen

A pain and fever relieving OTC* drug. Because of its safety and mild effectiveness, it is one of the most used oral medicine.[21] It is also proven to be effective when acetaminophen can be combined with other drugs, e.g. ibuprofen, both with lower doses.[22] 

  NSAIDs
If there isn’t any significant or positive response to the use of acetaminophen, NSAID is then recommended. NSAIDs are primarily used for joint pain.[22]  Despite its common use, the consumption of this drug should be limited to short-tem, in order to control episodic painful flares[21]and to prevent other side effects, such as myocardial infarction and stroke.

There are two forms of Nonsteroidal inflammatory drugs

  1. Oral NSAIDs
  2. Topical NSAIDs

Both forms are advised to contain cyclooxygenase 1 and 2 (COX-1 and COX-2) inhibitors, which help in gastric mucosa protection.

  Opioids
When there is a lack of reaction to NSAIDs, opioids are used. Both Tramadol and codeine contain opioids, which are refractory pain relieving medicines that are generally used for the treatment of moderate to severe knee OA.[21],[22]
  Intra-articular injections
Pain relieving fluids that are consumed if opioids aren’t sufficient. They are directly injected into the arthritic joint of the knee in full extension.[22] Hyaluronic acid and corticosteroids are examples of injected fluids.
  • OTC= Over-the-counter drug


Patients have to be prudent when taking medicines. All drugs have side effects, some more than other, thus it is very important that patients with other health issues verify if they may use a particular medication. Cardiovascular gastrointestinal are the most common side effects.

Some medications are not recommended for patients with OA, due to their unproven benefit or negative reactions:[21], [22] 


  Glucosamine sulfate and chondroitin sulfate
Glucosamine is a much used drug. Because of their lack of benefit, they are not recommended; ditto for chondroitin sulfate.[22]
  Topical capsaicin
Topical capsaicin creams contain extracts of chili pepper that activate a burning sensation.[22] Although many studies do not recommend those creams, other report that it is effective.


Physical Therapy Management[edit | edit source]

Pain is a common symptom that occurs in many levels (e.g. mild, moderate and severe). Exercises[20] (Level of Evidence 1A) have been proven to be effective as pain management and also improving physical functioning (e.g. muscle strengthening and aerobic condition) on short term.[4] (Level of Evidence 2A) In order to perform it correctly, exercises have to take place under the supervision of a health care professional such as a physiotherapist. When properly instructed these exercises can be performed at home, though research has shown that group exercise combined with home exercise is more effective.[23]  (Level of Evidence 1B) Aerobic walking, strengthening of the quadriceps, resistance training and tai chi are a few examples of exercises that can be efficacious for knee OA patients.[4] (Level of Evidence 2A)

When being treated, other aspects such as self-management and education, are of crucial importance as well.[20]  (Level of Evidence 1A)There are various forms of therapeutic interventions that may or may not be helpful for patients with knee OA:

  Hydrotherapy

Is a non-invasive and non-interventional therapeutic intervention that is recommended in international guidelines.[4] (Level of Evidence 2A) Although there is some contradictory evidence hydrotherapy can be useful in cases where pain is too grave to exercise on dry land. Many consider water-based exercises as a good preparation of exercise ashore. [24] (Level of Evidence 1A)

Knee osteoarthritis mostly affects the weight-bearing joints and leads, amongst other things, to pain and muscle weakness. The strength of muscles around the affected joints can be built up by graduated exercises making use of buoyancy and floats (in the later stage of the treatment).[25] (Level of Evidence AB) , [26](Level of Evidence 1B).[26] It has been shown that water buoyancy can reduce the weight that joints, bones and muscles have to carry.[27] (Level of Evidence 1B) Range of motion can also be maintained and increased[26] (Level of Evidence 1B)using the freedom of movement offered by the water with the support given by the buoyancy.

Functional difficulties of osteoarthritis patients are generally walking and climbing stairs and much can be done to re-educate such patients in the pool.[26] (Level of Evidence 1B). Many patients are more mobile in water than on land and this gives them greater confidence and a sense of achievement.

Examples of hydrotherapeutic exercises:

  • Stretching
  • Muscle strengthening
  • Aerobics

Despite the controversy, other studies show that aquatic exercises (Aquatherapy) have some short-term beneficial effects.[28](Level of Evidence 1B).Thus, the results indicate that hydrotherapy is applicable and efficient for patients with knee OA. Though there are short-term effects, long-term effects have yet to be investigated.[27] (Level of Evidence 1B) Aquatic exercise may therefore be considered as the first part of an exercise therapy program to get particularly disabled patients introduced to training.[28](Level of Evidence 1B).

  Manual therapy

Has proven effective to locate and eliminate factors like pain and joint immobility. However, it is only effective when combined with active exercise. This progress can enable further or advanced exercises. One study proved that manual therapy can relieve pain and decrease stiffness.[29] (Level of Evidence 1B)

  Massage therapy

Until recently massage has been proven not to be effective in the case of osteoarthritis. One study has shown that this therapeutic intervention, which uses both Swedish (including effleurage, pétrissage, fricition, tapotement and vibration) and the standard massage technique is safe, reduces pain and improves function.[30] (Level of Evidence 1B)

 Thermotherapy

Contrary to heat application, which did not have significant effects, ice massage and packs have showed to improve both ROM (range of motion) and physical function. Whether ice packs relieve pain is still unknown, thus further investigation is needed.[31] (Level of Evidence 1A)

 Electrotherapy

Transcutaneous electrical nerve stimulation is an example of electrotherapy, which has beneficial effects on relieving pain and improving physical function.[4],(Level of Evidence 2A) [32] (Level of Evidence 1B)TENS is a stimulation that uses electrical currents, which are applied directly to the skin and surrounding the knee.[4](Level of Evidence 2A) Despite the positive effects, electro stimulation is not effective on improving strengthening of the quadriceps.[28](Level of Evidence 1B) 

  Ultrasound

Older studies have claimed that this therapeutic option is not beneficial in the treatment of knee osteoarthritis. However, newer studies have shown that ultrasound reduces pain and improves the aerobic condition.[32] (Level of Evidence 1B), [33] (Level of Evidence 1A)

 External Support Devices

Braces:

Knee braces are used as a therapeutic procedure for patients with OA that involves the medial and lateral tibiofemoral compartments. Their purpose is to diminish the articular contact stress in those compartments. There are various types of braces [4]:(Level of Evidence 2A)

  1. “Rest” braces: are not advised due to weakening of the quadriceps muscle.
  2. Knee sleeves: maintain warmth and (mild) compression.
  3. Corrective braces: used by patients with moderate or severe knee OA. They provide and reduce compression of the joint and improve proprioception and strengthening of the quadriceps.

Taping:

Has proven to be slightly effective in decreasing pain and disability for patients with knee OA.[25] (Level of Evidence 1B) These beneficial effects are short-termed.

  Surgery and   post-operative   exercise

Surgery is only recommended when therapies are not effective. There are various types of knee OA surgery[4]: (Level of Evidence 2A)

  1. Arthroscopic surgery: Damaged cartilage will be removed. It only has short-term effects.
  2. Knee replacement surgery: It is proven to reduce pain and increase the mobility. This type of surgery has long-term beneficial effects.

Post- operative exercises are very much recommended. Exercises to improve the function of the new joint and muscle strengthening are most effective.[23] (Level of Evidence 1B)

Conservative Treatment:[edit | edit source]


Ottawa Panel of evidence suggests the use of therapeutic exercises or exercises with manual therapy to be most beneficial for patients with knee OA (Level of evidence 1A). [34] Cliborne et al. found short term benefits with hip mobilizations to decrease knee pain with functional tests including squatting.[35]  (Level of evidence 3b) Another article by Currier et al. developed a CPR for patients with knee pain to indicate those patients have knee OA, and which patients are likely to have short term benefits from hip mobilizations. Currier reports the “5 clinical prediction rules for this study include: 1. hip and groin parasthesia 2. groin pain 3.passive knee flexion less than 122 degrees 4.passive hip IR less than 17 degrees 5.Pain with hip distraction”.[36] If the patient has 2 variables then the positive likely hood ratio is 12.9. Deyle et al. found that knee mobilization gave statically improvements in WOMAC and 6 minute walk tests for both 4 week, 8 week, and 1 year follow up.[37] (Level of evidence 1b)

References[edit | edit source]

  1. Sharon Parmet, MS, Writer; Cassio Lynm, MA, Illustrator; Richard M. Glass, MD, Osteoarthritis of the Knee.JAMA. 2003;289(8):1068
  2. 2.0 2.1 Kuttner J.H., Goldberg V.M. 'Osteoarthritic Disorders'. American Academy of Orthopaedic Surg eons, 1995; Rosemont xxi - v. (Level of evidence: 1A)
  3. 3.0 3.1 J. W-P. Michael, et al., The Epidemiology, Etiology, Diagnosis, and Treatment of Osteoarthritis of the Knee, Deutsches Ärtzeblatt International, 2010, 107(9): 152–162 (Level of evidence: 2A)
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 RK Arya, Vijay Jain, Osteoarthritis of the knee joint: An overview, Journal Indian Academy of Clinical Medicine, 2013, 14(2): 154-62 (Level of evidence: 2A)
  5. Sagacious Studios. Osteoarthritis of the Knee. Available from: http://www.youtube.com/watch?v=IKC52uYdGQ4
  6. doctorsecrets. Osteoarthritis Explained Simply. Available from: http://www.youtube.com/watch?v=TczAeuc3J4E
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  8. Jennifer Reft. Knee Osteokinematics and Arthokinematics. Available from: http://www.youtube.com/watch?v=EyhiCvWER0Y [last accessed 07/12/2014]
  9. K. Uth, et al., Stem cell application for osteoarthritis in the knee joint: A minireview, World Journal of Stem Cells, 2014, 6(5): 629–636 (Level of evidence: 2A)
  10. J.A. Buckwalter, et al., Articular cartilage and osteoarthritis, 2005, 54: 465-480 (Level of evindence: 2C)
  11. A.D. Pearle, et al., Basic science of articular cartilage and osteoarthritis, Elsevier Sounders, 2005: 1-12 (Level of evidence: 2C)
  12. E. Schulte, et al., General anatomy and musculoskeletal system, Atlas of Anatomy, 2006: 372-373 (Level of evidence: 5)
  13. C. Logan, The knee joint, Idea health & fitness association, 2005, 2(1) (Level of evidence: 5)
  14. 14.0 14.1 14.2 S. Coleman, et al., A randomised controlled trial of a self-management education program for osteoarthritis of the knee delivered by health care professionals, arthritis research& therapy, 2012, 14: R21 (Level of Evidence: 1B)
  15. 15.0 15.1 G. Krucik, et al., Stages of Osteoarthritis of the knee, Healthline, 2013
  16. Ju Hee Ryu et al., Measurement of MMP Activity in Synovial Fluid in Cases of Osteoarthritis and Acute Inflammatory Conditions of the Knee Joints Using a Fluorogenic Peptide Probe-Immobilized Diagnostic Kit, theranostics, 2012 (Level of evidence: 2B)
  17. E. RINGDAHL, et al., Treatment of Osteoarthritis, American Family Physician, 2011, 83(11):1287-1292. (Level of evidence: 1B)
  18. Physiotutors. Signs & Symptoms of Knee Osteoarthritis. Available from: https://www.youtube.com/watch?v=JUH-ObEhXW8
  19. 19.0 19.1 EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis, W Zhang, M Doherty, G Peat, et al., Ann Rheum Dis 2010;69:483–489. doi:10.1136/ard.2009.113100 ( Quality level C : literature study)
  20. 20.0 20.1 20.2 20.3 20.4 T.E. McAlindon et al., OARSI guidelines for the non-surgical management of knee osteoarthritis, Osteoarthritis Research Society International, 2014, 22: 363-388 (Level of evidence: 1A)
  21. 21.0 21.1 21.2 21.3 M.C. Hochberg et al., Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee., American College of Rheumatology, 2012, 64(4): 465-474 (Level of Evidence: 5)
  22. 22.0 22.1 22.2 22.3 22.4 22.5 22.6 S. Kennedy, M. Moran, Pharmacological treatment of osteoarthritis of the hip and knee, BC Medical Journal, 2010, 52(8): 404-409 (Level of Evidence: 1A)
  23. 23.0 23.1 Supplementing a home exercise program with a class-based exercise program is more effective than home exercise alone in the treatment of knee osteoarthritis ,C. J. McCarthy, P. M. Mills1, R. Pullen, C. Roberts, A. Silman and,J. A. Oldham, Rheumatology 2004;43:880–886 (Level of evidence: 1B)
  24. Bartels et al., Aquatic exercise for the treatment of knee and hip osteoarthritis (Review),The Cochrane Library 2007, Issue 4 (Level of evidence : 1A)
  25. 25.0 25.1 Hinman, R.S., Heywood, S.E. (2007). Aquatic physical therapy for hip and knee osteoarthritis: results of a single-blind randomized controlled trial. Journal of Physical Therapy 87 (1), 32-43 (Level of evidence : 1B)
  26. 26.0 26.1 26.2 26.3 Wang, T., Belza, B., Elaine Thompson, F., Whitney, J.D., Bennett, K. (2007) Effects of aquatic exercise of flexibility, strength and aerobic fitness in adults with osteoarthritis of the hip or knee. Journal of Advanced Nursing, 57 (2), 141-152 (Level of evidence: 1B)
  27. 27.0 27.1 L.E. Silva et al., Hydrotherapy Versus Conventional Land-Based Exercise for the Management of Patients With Osteoarthritis of the Knee: A Randomized Clinical Trial, Physical Therapy Journal, 2008, 88(1): 12-21 (Level of Evidence: 1B)
  28. 28.0 28.1 28.2 A Clinical Trial of Neuromuscular Electrical Stimulation in Improving Quadriceps Muscle Strength and Activation Among Women With Mild and Moderate Osteoarthritis, Riann M. Palmieri-Smith, Abbey C. Thomas, Carrie Karvonen-Gutierrez, MaryFran Sowers, Physical Therapy - Volume 90 Number 10 October 2010 (Level of evidence : 1B )
  29. G.D. Deyle et al., Physical Therapy Treatment Effectiveness for Osteoarthritis of the Knee: A Randomized Comparison of Supervised Clinical Exercise and Manual Therapy Procedures Versus a Home Exercise Program, Physical Therapy Journal, 2005, 85(12): 1301-1317 (Level of Evidence: 1B)
  30. A.I. Perlman et al., Massage Therapy for Osteoarthritis of the Knee, Archives of Internal Medicine, 2006, 166: 2533-2538 (Level of Evidence: 1B)
  31. L. Brosseau et al., Thermotherapy for treatment of osteoarthritis (Review), The Cochrane Library, 2011, 10: 1-23 (Level of Evidence: 1A)
  32. 32.0 32.1 N.C. Mascarin et al., Effects of kinesiotherapy, ultrasound and electrotherapy in management of bilateral knee osteoarthritis: prospective clinical trial, BMC Musculoskeletal Disorders, 2012, 13: 182-191 (Level of Evidence: 1B)
  33. A. Loyola-Sánchez et al., Efficacy of ultrasound therapy for the management of knee osteoarthritis: a systematic review with meta-analysis, Osteoarthritis Research Society International Journal, 2010, 18: 1117-1126 Level of Evidence: 1A)
  34. No authors listed. Ottawa panel evidence-based clinical practice guidelines for therapeutic exercises and manual therapy in the management of osteoarthritis. Phys Ther. 2005 Sep; 85 (9):907-71.(Level of evidence 1A)
  35. Cliborne Amy, Rhon Dan, Judd Coy, Fee Terrance, Matekel Robert, Whitman Julie, Roberts Maj. Clinical hip tests and a functional squat test in patients with knee osteoarthritis: Reliability, Prevalence of Positive Test Findings, and Short-Term Response to Hip Mobilization. J Orthop Sports Phys Ther. 2004;34(11):676-685. doi:10.2519/jospt.2004.1432 (Level of evidence 3b)
  36. Linda L Currier, Paul J Froehlich, Scott D Carow, Ronald K McAndrew, Amy V Cliborne, Robert E Boyles, Liem T Mansfield and Robert S Wainner. Development of a Clinical Prediction Rule to Identify Patients With Knee Pain and Clinical Evidence of Knee Osteoarthritis Who Demonstrate a Favorable Short-Term Response to Hip Mobilization. PHYS THER Vol. 87, No. 9, September 2007, pp. 1106-1119
  37. Deyle Gail, Henderson Nancy, Matekel Robert, Ryder Micahel, Garber Matthew, Allison Stephen. Effectiveness of Manual Physical therapy and Exercise in Osteoarthritis of the Knee A Randomized, Controlled Trial (Level of evidence 1b)

37. Seyed Mansour Rayegani 1 , Seyed Ahmad Raeissadat 1 , Saeed Heidari 2 , Mohammad Moradi-Joo 3,4. Safety and Effectiveness of Low-Level Laser Therapy in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. S12–S19 2017 Aug 29. (Level of evidence 1A)