Author(s): Glenn Sapp, MD FAAPMR, Jared Stowers, MD
Originally published: November 10, 2011 Last updated: July 11, 2024
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Disease/Disorder

Definition

Osteoarthritis (OA) is a disease mostly affecting the articular cartilage, the entire joint including the synovium and the subchondral bone. The reference to it as a degenerative joint disease is no longer appropriate as it is not only due to “wear and tear” but may also be due to abnormal mechanics, inflammation, post-surgery, etc.1 OA can be primary or secondary.

Etiology

  • Primary
    • Idiopathic (e.g., aging persons, females)
    • Familial
  • Secondary
    • Abnormal forces across joint (post-traumatic)
    • Abnormal articular cartilage (rheumatologic diseases)

Predisposing factors include:

  • Trauma/micro-trauma from chronic repetitive motion
  • Infection
  • Joint inflammatory conditions (e.g., rheumatoid arthritis)
  • Neuromuscular/neuropathic disorders (e.g., Duchenne muscular dystrophy)
  • Metabolic disorders (e.g., osteoporosis)
  • Endocrine disorders (e.g., acromegaly)
  • Obesity
  • Hemoglobinopathies (e.g., sickle-cell disease)
  • Bone disorders, other orthopedic disorders (e.g., Paget disease, avascular necrosis)
  • Medications (corticosteroids and injectable anesthetics may be chondrotoxic)

Epidemiology including risk factors and primary prevention

  • Frequency: More than 50% of adults over age 65 have OA. OA affects more than 30 million people in the US and over 302 million people worldwide.2
  • Morbidity: Associated with pain, loss of function, and reduced endurance leading to weight gain. While OA is not directly causative of mortality, recent studies have correlated OA with increased all-cause mortality. This is thought to be associated with multiple factors including increased disability, loss of mobility, and polypharmacy.3
  • Studies have found associations between the epidemiology of OA and race/ethnicity. For example, knee OA has a higher prevalence in African Americans, particularly women.4
  • Socioeconomic status has been associated with an increased incidence of OA and poorer outcomes.4
  • Equally prevalent in men and women before age 55, but increases in women thereafter, with higher rates in knees in women, and hips in men.5,6The increased incidence of OA in women after the age of 55 is believed to be associated with menopausal hormonal changes. This is most notably seen in hand osteoarthritis, which has a significantly increased incidence in women after the age of 50 compared to men.7 It is the most common joint disorder worldwide affecting 10% of men and 18% of women over 60 years old.5,6

Patho-anatomy/physiology

The usual mechanism is repetitive microtrauma and direct damage with the associated immune changes in the articular cartilage of predominantly the weight-bearing joints, such as the knees. Initially, there is swelling of the cartilage from increased proteoglycan synthesis, release of cytokines, and metalloproteinases-associated inflammation. Hypertrophic repair of the cartilage can progressively occur for years. Reduced joint space from cartilage loss occurs with decreased proteoglycan synthesis and diminished cartilage elasticity, formation of clefts and fibrillations leading to exposure of the subchondral bone, microfracture, new bone formation, bone cysts from necrosis, and osteophyte formation. Other joint structures like the synovium, ligaments and surrounding neuromuscular structures may be affected, (e.g., atrophy, contractures).8

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

  • Mild: Intermittent pain/mild discomfort with very little cartilage damage in line with Outerbridge grade 1.
  • Moderate: Increased pain, associated swelling/effusion, crepitus and early wasting of muscles with more extensive damage to the articular cartilage and evidence of inflammation in line with Outerbridge grades 2 overlapping with 3.
  • Severe: Along with the moderate features, cartilage becomes extensively denuded, subchondral bone is exposed and severe muscle wasting occurs. The joint may be deformed secondary to severe wear of the cartilage, soft tissues and subchondral bone, e.g., genu varum deformity, in line with Outerbridge grades 3/4.
  • Outerbridge stages based on arthroscopic findings are9
    • Grade 1- softening and swelling
    • Grade 2- fragmentation and fissuring of less than 0.5 inches
    • Grade 3-fragmentation and fissuring at or greater than 0.5 inches
    • Grade 4- erosion down to the subchondral bone

Specific secondary or associated conditions and complications

  • Obesity10
  • Falls
  • Chronic pain syndromes
  • Nerve irritations/damage, e.g., cervical radiculopathy/myelopathy
  • Increased bursae formation
  • Fatigue, stress and frustration/depression

Essentials of Assessment

History

History for joint pain/discomfort with activities and relieved with rest but becoming persistent; morning joint stiffness, swelling, weakness.

Physical examination

Physical examination for muscle atrophy, joint deformities/malalignment, effusions, joint-line tenderness, crepitus, antalgic gait, palpable/visible evidence of osteophytes, limited range of motion with stiffness/periarticular muscle spasms, Heberden nodes at the distal interphalangeal (DIP) joints and Bouchard nodes at the proximal interphalangeal (PIP) joints of the hands.

Functional assessment

  • Mobility assessment: Observe walking distance, and whether pain control and endurance can be improved with assistive devices. Gait analysis in hip/knee/spinal OA may be required.
  • Self-care assessment for activities of daily living.
  • Full assessment for depression when psychosocial stressors and chronic pain exist.

Laboratory studies

Erythrocyte sedimentation rate (ESR) may be elevated in generalized or in erosive inflammatory OA. C-reactive protein (CRP) may be elevated in associated inflammation. Synovial fluid analysis shows clear fluid with white blood cell count 2000/microliter with mononuclear predominance.

Imaging

  • Plain x-ray shows arthritis well but may be negative at the early stage of the disease. The Kellgren-Lawrence grading is
    • Osteophytes
    • Joint space narrowing
    • Subchondral sclerosis
    • Subchondral cyst formation
  • Magnetic resonance imaging (MRI): Required if there is difficulty in diagnosis using x-ray (e.g., osteonecrosis of hips/knees); or concomitant soft-tissue pathology since MRI can best image soft-tissue injuries.
  • Computerized tomography (CT): useful in advanced OA to define small intra-articular bodies.
  • Bone scans: differentiate from other causes of joint pain (e.g., osteomyelitis, tumors).
  • Ultrasound imaging: Non-invasive, radiation-free imaging modality that can be used to detect structural and inflammatory abnormalities in joints affected by OA.11 Can be utilized as a clinical diagnostic tool or therapeutically to assist with intra-articular injections. The ACR strongly recommends the utilization of imaging modalities, including ultrasound, when performing intra-articular hip injections. The use of ultrasound is suggested for all other intra-articular injections if available to ensure the safety and accurate delivery of medication into the joint.12

Supplemental assessment tools

  • Arthroscopy: for visual inspection of the joint and washing out intra-articular debris for pain relief.
  • Arthrocentesis: allows fluid analysis, gram stain, culture, and birefringence under polarized light, etc. A steroid injection trial could be diagnostic and therapeutic if pain relief occurs.
  • Electrodiagnosis: to explore unexplained sensory symptoms or weakness.
  • Goniometry: Used to assess the range of motion at an arthritic joint. Multiple studies have shown significant utility in assessing ROM as an outcome measure to aid in therapeutic modalities.13
  • Pain assessment tools: to define the level of pain initially/as an outcome of treatment.

Early predictions of outcomes

  • Improved outcomes and slowing of disease progression are associated with early OA diagnosis with a treatment plan focused on pain alleviation and rehabilitation.
  • A history of trauma affecting the joint’s articular surface leads more often to posttraumatic OA than does a history of non-traumatized joints.
  • Patients able to partake in regular exercises tend to show more functional improvement and the ability to cope with the pain.

Environmental

Studies have shown that changes in atmospheric pressure are associated with increased pain levels in patients with osteoarthritis. However, more research is required to determine the association of other weather factors such as precipitation and temperature on arthritic pain and functional scores.14

Depending on the joints affected, patients find it difficult to negotiate uneven terrain during community ambulation and outdoor activities.

Social role and social support system

Pain and functional compromise can challenge social integration. Assistive devices may increase a feeling of “standing out”. Patient education in exercise programs, medication use, and regular follow-up with physicians may reduce these helpless feelings.

Professional issues

Medicolegal pitfalls exist from the prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs). Complications include associated gastrointestinal, cardiovascular, renal, and hepatic side effects and have resulted in legal action. Physicians also need to rule out systemic or malignant causes of pain, even when OA may be a main or partial contributor. Other issues include the frequency of steroid injection administration, the cost-benefit to the patient paying out of pocket for procedures such as platelet-rich plasma (PRP) and other regenerative medicine options, acupuncture, and massage therapy.

Rehabilitation Management and Treatments

Coordination of care

The ideal approach to treatment should be a coordinated and integrated multidisciplinary approach involving physiatrists, rheumatologists, orthopedists, pain physicians, physical therapists, occupational therapists, social workers, etc.

Patient & family education

The American Academy of Rheumatology (ACR) recommends a multimodal approach to the treatment of OA including extensive patient/family counseling and shared decision-making. Counseling, including lifestyle changes and weight reduction, joint protection techniques, exercise programs, and medication management should be performed in a manner that accounts for patient preferences and acknowledges the available resources and potential barriers that a patient may have completing their treatment plans.12

Emerging/unique interventions

Impairment-based measurement

  • Functional capacity evaluation/vocational assessment assesses the ability to cope and adapt to work demands and environment.
  • Refer to the Imaging section.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Early diagnosis, thorough workup, and comprehensive treatment are keys to improving clinical outcomes.
  • Rehabilitation and exercise prescriptions should work towards improving functional capacity and decreasing extent of disability.  Specifically focusing on muscle strengthening and stretching around pathologic joints.
  • NSAIDs are a mainstay of pharmacological management of OA. Acetaminophen is also an appropriate oral analgesic though placebo trials have suggested little long-term benefit. For patients with knee and hip OA, tramadol is recommended over non-tramadol opiates. The prescription of non-tramadol opiates is conditionally recommended against in the management of OA except in circumstances where other systemic agents are contraindicated/have been exhausted due to the risks of toxicity and dependence.15 Patients should be actively monitored by their prescribing physician for medication complications.
  • Topical NSAIDs are strongly recommended in patients with knee OA when not contraindicated medically.16 They are conditionally recommended in hand OA. Topical capsaicin cream can be beneficial in knee OA.
  • Weight loss is essential. A 5kg weight gain increases the risk of developing knee OA by 36%.17 Studies reflect a dose-response with weight loss and symptom and functional improvement in patients with OA. As little as a 5% body weight loss can result in improved clinical outcomes.
  • Mobility-focused and specific exercise programs are key components of a holistic exercise prescription. Balance exercises are recommended for patients with lower extremity OA involving the knees and hips. Tai Chi and Yoga promote movement and strengthening while also encouraging principles of relaxation and mindfulness.
  • Bracing is recommended for patients whose ambulatory function is limited by their OA. Kinesiotaping can provide proprioceptive feedback on affected joints while allowing for range of motion at that joint. Patients with knee and hip OA are not recommended to utilize modified shoes due to a lack of consensus data on optimal footwear.
  • Modalities and thermal interventions delivered by hot/cold packs, ultrasound, and diathermy are conditionally recommended for patients with knee, hip, and hand OA. Paraffin wax treatments have shown improved pain scores and reduced surrounding muscle tenderness in a small, randomized control trial.18
  • Many supplements including fish oil, glucosamine, and chondroitin sulfate are not recommended in OA treatment due to a lack of proven efficacy in literature and increased risk of side effects and medication interactions. 
  • Definitive Management for End-stage Osteoarthritis is determined when patients have exhausted conservative management.19 In most cases, frequently involving the knee, hip, and shoulder, Total Joint Arthroplasty (TJA) is recommended as definitive management. TJA involves the removal of the native joint and replacement with a metal, plastic, or ceramic prosthesis.  In other joints, such as the ankle, arthrodesis (joint fusion) is the gold standard for the treatment of severe osteoarthritis.20  

Cutting Edge/Emerging and Unique Concepts and Practice

Emerging/unique interventions include:

  • Disease-modifying therapies such as doxycycline/tetracycline have shown some evidence in the literature of being able to decrease cartilage degeneration.21
  • Surgical innovations utilizing regenerative medicine to culture and implant chondroblasts/cartilage from patients’ autologous cartilage to replace worn joint cartilage.22
  • Pulsed electromagnetic field stimulation (PMFS) is approved by the US Food and Drug Administration.23
  • Vitamin D supplementation in OA has been associated with improved pain scores.24,25
  • Orthobiologic therapies such as platelet-rich plasma, bone marrow, and adipose mesenchymal stem cell (MSC) transplantation are continuing to be studied. A higher platelet dose for PRP appears to be more effective, yet the optimal dosage and preparation method are not standardized.26
  • Perineural injection of local anesthetics to peripheral nerves that supply painful arthritic joints can be both diagnostic and therapeutic for the analgesic management of OA.27 If peripheral nerve blocks are successful, radiofrequency ablation of the sensory nerve has been established as a safe and effective method to provide longer-term pain management.28
  • Genicular artery embolization is an emerging embolotherapy that targets the pro-inflammatory state in OA associated with neovascularity, angiogenesis, and the germination of sensory nerves thought to be responsible for hyperalgesia.29,30

Gaps in the Evidence-Based Knowledge

Currently, there is a lack of preponderant evidence to support the use of regenerative therapies and orthobiologics such as mesenchymal stem cell therapy, platelet-rich plasma, and hyaluronic acid injections.31 While some studies suggest medium-term benefits of PRP and stem cell therapies, more research is required.31,32

The immediate standard of care for OA includes methods to control pain, reduce ongoing joint deterioration, and promote activity/behavioral modifications. There are no disease-modifying agents with evidence strong enough to warrant recommendation. Currently, there are Phase 2 and 3 trials ongoing to assess the efficacy of disease-modifying therapies in the treatment of OA.

References

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  3. Wang, Y., Nguyen, U.-S.D.T., Lane, N.E., Lu, N., Wei, J., Lei, G., Zeng, C. and Zhang, Y. (2021), Knee Osteoarthritis, Potential Mediators, and Risk of All-Cause Mortality: Data From the Osteoarthritis Initiative. Arthritis Care Res, 73: 566-573. https://doi.org/10.1002/acr.24151
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  12. Kolasinski, S.L., Neogi, T., Hochberg, M.C., Oatis, C., Guyatt, G., Block, J., Callahan, L., Copenhaver, C., Dodge, C., Felson, D., Gellar, K., Harvey, W.F., Hawker, G., Herzig, E., Kwoh, C.K., Nelson, A.E., Samuels, J., Scanzello, C., White, D., Wise, B., Altman, R.D., DiRenzo, D., Fontanarosa, J., Giradi, G., Ishimori, M., Misra, D., Shah, A.A., Shmagel, A.K., Thoma, L.M., Turgunbaev, M., Turner, A.S. and Reston, J. (2020), 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res, 72: 149-162. https://doi.org/10.1002/acr.24131
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  16. Brophy, Robert H. MD; Fillingham, Yale A. MD. AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition. Journal of the American Academy of Orthopaedic Surgeons 30(9):p e721-e729, May 1, 2022. | DOI: 10.5435/JAAOS-D-21-01233
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  21. Shanmugasundaram S, Solanki K, Saseendar S, Chavada VK, D’Ambrosi R. Role of Doxycycline as an Osteoarthritis Disease-Modifying Drug. J Clin Med. 2023 Apr 18;12(8):2927. doi: 10.3390/jcm12082927. PMID: 37109263; PMCID: PMC10145123.
  22. Thoene M, Bejer-Olenska E, Wojtkiewicz J. The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review. Int J Mol Sci. 2023 May 18;24(10):8925. doi: 10.3390/ijms24108925. PMID: 37240271; PMCID: PMC10219560.
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  26. Hohmann, Erik. “High Platelet Dose PRP May be the Nonoperative Treatment of Choice for Knee Osteoarthritis.” Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, S0749-8063(24)00269-X. 9 Apr. 2024, doi:10.1016/j.arthro.2024.03.046
  27. Knight B, Walker J, Nair LS. Perineural local anesthetic treatments for osteoarthritic pain. Regen Eng Transl Med. 2021 Sep;7(3):262-282. doi: 10.1007/s40883-021-00223-0. Epub 2021 Sep 10. PMID: 36275437; PMCID: PMC9585910.
  28. Zhang H, Wang B, He J, Du Z. Efficacy and safety of radiofrequency ablation for treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. J Int Med Res. 2021 Apr;49(4):3000605211006647. doi: 10.1177/03000605211006647. PMID: 33887985; PMCID: PMC8072859.
  29. Changhao Sun, Yuxin Chen, Zhiling Gao, Longyun Wu, Rong Lu, Chaoyun Zhao, Hao Yang, Yong Chen. Genicular artery embolization for the treatment of knee pain secondary to mild to severe knee osteoarthritis: One year clinical outcomes. European Journal of Radiology. Volume 175. 2024. 111443. ISSN 0720-048X. https://doi.org/10.1016/j.ejrad.2024.111443.
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  31. A Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH. Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med. 2017 Aug. 51 (15):1125-1133.
  32. Cui GH, Wang YY, Li CJ, Shi CH, Wang WS. Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of the knee: A meta-analysis. Exp Ther Med. 2016 Nov. 12 (5):3390-3400

Original Version of the Topic 

Segun Dawodu, MD. Osteoarthritis. 01/24/2013.

Previous Revision(s) of the Topic 

Segun Dawodu, MD. Osteoarthritis. 4/4/2017.

Segun Dawodu, MD. Osteoarthritis. 5/12/2021

Author Disclosure

Glenn Sapp, MD FAAPMR
Nothing to Disclose

Jared Stowers, MD
Nothing to Disclose