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Osteoarthritis

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Contents

Other Names

  • Arthritis
  • Arthur
  • Osteoarthritis (OA)
  • “wear-and-tear” arthritis
  • Age-related Arthritis
  • Degenerative Joint Disease (DJD)
  • Degenerative Arthritis

Background

  • This page covers general osteoarthritis
    • Note each joint has a specific page

History

Epidemiology

  • General
    • Most common joint disease in the world
    • Statistics vary somewhat depending on definition of OA being used
    • Murphy et al estimated estimated the lifetime risk of developing symptomatic knee OA to be 40% in men and 47% in women[1]
    • In 2017, affected 303 million people globally[2]
  • Prevalence
    • Affects 10% of men, 18% of women over 60 years of age[3]
    • Framingham study: prevalence was 19.2% among participants over 45[4]
    • Johnston County Osteoarthritis Project: prevalence was 27.8% among participants over 45
    • NHANES III: 37% of patients over 60 had radiographic evidence of knee OA
  • Incidence
    • Hip OA: 88 per 100,000 person-years[5]
    • Knee OA: 240 per 100,000 person-years
    • Hand OA: 100 per 100,000 person-years

Economic Burden

  • In developed countries, estimated to cost between 1 - 2.5% of GDP[6]
  • Arthritis is responsible for more disability in the US workforce than any other factor[7]
  • Approximately 21.6% of US adults (46.4 million) reported physician-diagnosed arthritis in 2005[8]
    • This number is projected to skyrocket by 40% to nearly 67 million by 2030
  • 2004: Arthritis drained approximately $281.5 billion from the US economy, an increase of 53% from 1996[9]

Pathophysiology

Definition

  • Radiographic
    • Presence of a definite osteophyte (Grade ≥2 on kellgren-lawren classification)[10]
    • More severe grades by the presumed successive appearance of joint space narrowing, sclerosis, cysts, and deformity
    • Note, MRI is more sensitive for soft tissue changes but not required for diagnosis
  • Clinical
    • Generally defined as presence of pain, aching or stiffness with radiographic findings consistent with OA
    • Not all patients with joint symptoms have radiographic OA[11]
    • Not all patients with radiographic OA have clinical disease

Cartilage

  • Type II collagen most important structural protein
  • Chondrocytes regulate cartilage architecture, biomechanical composition
  • When activated, chondrcytes release multiple inflammatory cytokines including TNF-alpha, IL-6, IL-1, metalloproteinases, disintegrin
  • In osteoarthritis, the immune system is activated by damage-associated molecules including glycosaminoglycans, hyaluronon[12]
  • Calcium pyrophysphate and sodium urate crystals also bind to chondrocytes
  • It is unclear if chondrocytes are primarily activated from cartilage degredation or secondarily from other joint structures

Subchondral Bone

  • Forms anchor between articular cartilage and trabecular bone
  • Osteoblasts respond to mechanical stimulation similar to chondrycytes[13]
  • Pronounced changes occur in subchondral bone in osteoarthritis[14]
  • Radiographs evidence includes osteophytes, subchondral cysts, subchondral sclerosis
  • MRI can also demonstrate microfractures at different stages of healing[15]
  • One study suggested that subchondral degeneration may precede cartilage degeneration[16]
  • Subchondral bone is highly innervated and contributes to pain generation[17]

Synovium

  • Inflammation of the synovium, termed synovitis, is a commonly seen in osteoarthritis
  • Synoviocytes are noted to proliferate under arthritic stress, producing hyaluronic acid and lubricin[18]
  • In physiologically normal patients, these proteins provide lubrication and reduced stress load
  • In patients with osteoarthritis, they demonstrate reduced lubrication and stress reduction[19]
  • Synoviocytes also release inflammatory markers similar to osteoblasts and chondroblasts

Systemic Inflammation

  • In general, osteoarthritis is considered a localized pathologic state and not a systemic illness
  • 2013 systematic review: C-reactive associated with symptoms but not radiographic findings[20]

Risk Factors

General

  • Age (#1 Risk Factor)[21]
  • Women > Men
    • More likely to have OA[22]
    • OA is more severe in women
  • Estrogen
    • Conflicting results, regardless of whether endogenenous or exogenous[23]
  • Race
    • Less common in Chinese than white[24]
    • African Women (23%) similar to white women (22%); African men (21%) higher than white men (17%)[25]
  • Trauma
  • Genetics
    • Twin studies estimate the heritable component of OA to be between 50% - 65%[26]
  • Injuries
  • Occupation
    • Repetitive labor
    • Occupations that require carrying, kneeling, squatting
  • Sports
    • Studies have produced conflicting results
    • Physical Activity: High life time physical activity associated with knee OA[29] and hip OA[30]
    • Long Distance Runners: Hip OA[31], Knee OA[32]
    • Soccer Players: Knee OA[33]

Medical Conditions

  • Obesity
    • Most notable for hip and knee[34]
    • Weight loss associated with reduction in risk[35]
  • Gout

Diet & Nutrition

  • Vitamin D
    • Overall, mixed results
    • Low vitamin D associated with increased risk of progression of knee OA compared to individuals with higher vitamin D [36]
    • Serum vitamin D levels were not associated with the risk of hip OA[37]
    • 2 cohort studies failed to confirm any protective effect of vitamin D supplementation on the structural worsening of knee OA[38]
  • Vitamin C
    • Low vitamin C dietary intake was associated with an increased risk of progression, but not incidence, of both radiographic and symptomatic knee OA[39]
  • Vitamin E
    • Supplementation with vitamin E failed to ameliorate symptoms in patients who had symptomatic knee OA or to prevent knee OA progression[40]
  • Selenium
    • Animal studies: low selenium associated with irregular bone formation, decreased bone strength, and abnormalities in type I and II collage in cartilage[41]
    • China: Low selenium associated with increased risk of kashin-beck disease, a form of arthritis, and risk was reduced with selenium supplementation[42]
    • Another study found high selenium intake was significantly associated with increased risk of both hip and knee OA[43]
  • Vitamin K
    • Neogi et al: Low vitamin K associated with osteoarthritis of the hand and knee[44]

Hand

  • Dominick et al: inverse association between grip strength and carpometacarpal OA; between pinch strength and metacarpophalangeal OA[45]
  • Framingham study: Increased grip strength associated with increased risk of hand OA[46]

Hip

Knee

List of Osteoarthropathies

Upper Extremity

Torso

  • Needs to be updated

Lower Extremity

Clinical Features

  • History
    • Symptoms that correlate with radiographic findings and no other clear etiology
    • Most patients report a painful range of motion; range of motion often decreased
    • Most patients report pain in the affected joint, worse with activity or use of the affected limb
    • In weight bearing joints, ambulation, stairs and activity typically make it worse
    • Patients may endorse swelling, deformity, crepitus
  • Physical Exam
    • In early stages, the exam may be relatively normal
    • In advanced stages, joint deformity is common
    • Tenderness to the affected joint
    • Effusion may be present
    • Painful and often limited arc of motion

Evaluation

Radiographs

  • Radiographic features:
    • 3 View radiograph of affected joint is standard
    • Loss of the joint space width (sensitive, not specific)[51]
    • Osteophyte formation
    • Subchondral sclerosis and cysts

MRI

  • General
    • More sensitive for early osteoarthritis changes as it better evaluates soft tissue abnormalities[52]
    • Cartilage morphology predicts disease progression (population level only)[53]
    • Scoring systems exist for knee, hip and hand

Ultrasound

  • General
    • Gaining popularity as a diagnostic modality[54]
    • Can assess synovium, effusion

CT

  • General
    • Not a significant role in the evaluation of suspected osteoarthritis

Classification

Kellgren and Lawrence (KL) Classification

  • Originally proposed for classifying knee OA, now more broadly applied to all joints
  • Grade 0: no radiographic features of OA present
  • Grade 1: doubtful joint space narrowing, possible osteophytic lipping
  • Grade 2: definite osteophytes, possible joint space narrowing on anteroposterior weight-bearing radiograph
  • Grade 3: multiple osteophytes, definite joint space narrowing, sclerosis, possible bony deformity
  • Grade 4: large osteophytes, marked joint space narrowing, severe sclerosis and definite bony deformity

Management

Lifestyle Modification

Weight Loss

  • In obese patients without osteoarthritis, weight loss reduces the risk of developing osteoarthritis[55]
  • In obese patients with osteoarthritis, weight loss improves symptoms of disease[56]
  • Weight loss was associated with increased type II collagen (cartilage synthesis) and decrease cartilage oligomeric matrix protein, a biomarker of cartilage degredation. These changes also correlated with reduced insulin levels and insulin resistance.[57]
  • Improvement in cardiovascular health and all cause mortality

Exercise

  • When combined with weight loss, superior to exercise or weight loss alone[58]

Oral Medications

Acetaminophen

  • Cochrane review: Superior to placebo for pain relief[59]
  • Similar to placebo for physical function, stiffness
  • NNT 4-16, fewer GI side effects than NSAIDS

NSAIDS

  • Considered superior to Acetaminophen for pain relief
  • Also helps with stiffness, global function, physical function
  • Patients should be made aware of gastrointestinal, renal and cardiovascular risks
    • For people with adverse GI side effects, adding a PPI can help relieve symptoms[60]
  • This class of medications is contraindicated in some patients

Opioids

  • Should only be prescribed when non-opioid medications fail to control pain
  • Prescribed at the lowest dose with careful monitoring
  • Strongly encouraged to involve pain management if patients on long term opioids

Doxycycline

  • Inhibits matrix metalloproteinases
  • Helped with joint space narrowing, no improvement in pain or function[61]
  • Benefits outweighed by adverse events

Bisphosphonates

  • General
    • Inhibition of osteoclast activity may reverse subchondral bone changes
  • Knee Osteoarthritis
    • In a small study, risedronate significantly reduced markers of cartilage degradation and bone resorption at 1 year follow up[62]
    • In a much larger study, risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed[63]
    • In a small study, zoledronic acid reduced knee pain, size of bone marrow lesions over 6 months[64]

Strontium Ranelate

  • General
    • Used for osteoporosis, stimulates calcium receptors and increases bone formation
    • Poorly researched for use in osteoarthritis
  • Knee Osteoarthritis
    • Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.[65]

AMG 108

  • Is a mnoclonal antibody against the interleukin 1 receptor
  • Demonstrated statistically insignificant but numerically greater improvements in pain; however, minimal, if any, clinical benefit was observed.[66]

Adalimumab

  • General
    • Trade name is Humira
    • Is a monoclonal antibody to TNFα
  • Hand Osteoarthritis
    • No difference in disease progression between adalimumab and placebo at 12 months follow up[67]
  • Knee Osteoarthritis
    • This small, non-blinded study showed improvement in pain, stiffness, function and joint swelling at 12 weeks[68]

Tricyclic Antidepressants

  • Imipramine demonstrated no difference in pain when compared to placebo, however there was a slight improvement in grip strength[69]

Topical Medications

Capsaicin

  • Safe, well tolerated, no systemic toxicity
  • Application site burning pain peaks at one weak and resolves over time
  • Administered four times daily, capsaicin is moderately effective in reducing pain intensity up to 20 weeks regardless of site of application and dose in patients with at least moderate pain and clinical or radiologically defined OA, and is well tolerated.[70]

Topical NSAIDS

  • Recommended by governing bodies for hand and knee OA[71]
  • Topical and oral NSAIDs demonstrate an equivalent effect on knee pain over 1 year of treatment, with fewer adverse events due to lower systemic absorption of topical NSAIDs compared with oral NSAIDs[72]

Supplements

Chondroitin And Glucosamine

  • Demonstrate anti-inflammatory, anti-catabolic properties in vitro[73]
  • Overall literature, systematic reviews and governing bodies have not indicated any clinically relevant benefits[74]

Fish Oil

  • General
    • Used for a variety of ailments in addition to OA
    • Contains omega-3 polyunsaturated fatty acids
    • Anti-inflammatory and chondroprotective in animal studies
  • Hip/Knee OA
    • In a double blinded RCT, No benefit when added to glucosamine compared to placebo[75]

S-adenosylmethionine (SAMe)

  • Soeken et al meta-analysis: similar effect to NSAIDS in reducing pain, improving function with fewer adverse events[76]
  • Note, limited to only 2 studies

Methylsulfonylmethane (MSM)

  • Knee OA
    • When combined with glucosamine compared to glucosamine alone, there was increased efficacy in reducing pain and swelling and in improving the functional ability of joints than the individual agents[77]
    • Kim et al: randomized, double blinded RCT MSM twice a day improved symptoms of pain and physical function over the 12 week study period[78]

Collagen Hydrolysate

  • General
    • Collagen hydrolysate ingestion stimulates a statistically significant increase in synthesis of extracellular matrix macromolecules by chondrocytes[79]
  • Knee OA
    • Two small studies suggest that it helps with pain from knee OA[80][81]

Passion Fruit Peel Extract

  • Knee OA
    • In a small, randomized, double-blinded placebo controlled study, there was a statistically significant reduction in pain, stiffness, physical function and WOMAC score compared to placebo[82]

Curcuma Longa Extract

  • Knee OA
    • In this small, randomized, single blind, placebo-controlled trial of patients with primary knee OA, curcuma longa extract showed significant decrease knee pain[83]
    • Additionally shown to reduce serum levels of inflammatory markers IL-1, malondialdehyde[84]

Boswellia Serrata Extract (BSE)

  • Knee OA
    • In a randomized double blind placebo controlled crossover study had statistically significant decrease in knee pain and swelling, increased flexion and walking[85]
    • BSE showed a slower onset of action but the effect persisted even after stopping therapy compared to valdecoxib[86]

Curcumin

  • General
    • In patients with undefined arthritis, a brand-name formulation succesfully improved WOMAC score, walking distance and decreased CRP[87]

Pine Bark Extract

  • General
    • Brand name Pycnogenol
    • Exerts antioxidative, anti-inflammatory, and chondroprotective effects in vitro and in vivo
    • Provides long-lasting positive effects such as enhanced physical mobility and pain relief for patients with mild OA[88]
  • Knee OA
    • In 100 patients with knee OA randomized to pine bark extract or placebo, pations reported inmproved WOMAC score and alleviation of pain compared to placebo[89]

L-Carnitine

  • Knee OA
    • In a randomized double-blind placebo-controlled trial trial of women with knee OA, Kolahij et al found 750 mg/day was superior to placebo for pain reduction, stiffness, physical function and WOMAC score[90]

Physical Therapy

General

  • Hip OA
    • Bennell et al found physical therapy did not result in greater improvement in pain or function compared with sham treatment[91]
  • Knee OA
    • Meta-Analysis (Want et al)[92]
      • Low-strength evidence that aerobic exercise, aquatic exercise improved disability
      • Aerobic exercise, strengthening exercise, and ultrasonography reduced pain and improved function
      • Short- but not long-term follow-up proprioception exercise reduced pain and Tai Chi improved function.

Low Level Laser Therapy (LLLT)

  • Knee OA
    • When combined with exercise, effective in yielding pain relief, function and activity compared to placebo[93]

Complementary and Alternative Medicine

Acupuncture

  • Chen et al: No improvement in symptoms when acupuncture was combined with physical therapy compared to physical therapy alone [94]

Intra-Articular Injections

Corticosteroid Injection

  • General
    • Intra-articular (IA) corticosteroid injections are commonly used for pain relief in primary and secondary care
  • Knee OA
    • The research evidence demonstrates that IA CS injections provide short term reduction in OA pain and can be considered as an adjunct to core treatment for the relief of moderate to severe pain in people with OA[95]
    • 2015 Cochrane review: suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection[96]

Dextrose Prolotherapy

  • General
    • Injection of dextrose into pathologic joint in order to generate an inflammatory process
    • Note: injectant can be substance other than dextrose, however dextrose most common
  • Knee OA
    • Rahimzadeh et al found that prolotherapy decreased WOMAC scores. Note they also found PRP to be superior to prolotherapy [97]
    • 3 Arm study: Dextrose prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises[98]

Viscosupplementation

  • General
    • Hyaluronic acid is a naturally ocurring glycosaminoglycan (GAG) found in synovial fluid that can acts as a lubricant
    • Sometimes referred to as visco, viscosupplementation, or rooster comb
  • Knee Osteoarthritis
    • 2012 meta-analysis:No clinically relevant benefit for pain relief[99]
    • Subsequently has fallen out of favor but still a non-surgical option

Lubricin

  • General
    • Glycoprotein that acts synergistically with Hyaluronic acid
    • Minimal research at this time, however offers therapeutic potential
    • Supplementation restores normal joint lubrication and might be chondroprotective[100][101]

Anakinra

  • General
    • Recombinant antagonist of interleukin-1 receptor
  • Knee OA
    • Anakinra was well tolerated as a single 50‐mg or 150‐mg intraarticular injection in patients with OA of the knee.
    • However, anakinra was not associated with improvements in OA symptoms compared with placebo.[102]

Sprifermin

  • General
    • also known as recombinant human fibroblast growth factor 18 (rhFGF18)
  • Knee OA
    • Intra-articular administration of 100 μg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance[103]

Regenerative Medicine

Stem Cell Therapy

  • General
    • Poorly understood and studied

Platelet Rich Plasma

  • Knee OA
    • Systematic review: PRP injection results in significant clinical improvements up to 12 months postinjection. Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months postinjection.[104]

Dextrose Prolotherapy

  • General
    • Injection of dextrose into pathologic joint in order to generate an inflammatory process
    • Note: injectant can be substance other than dextrose, however dextrose most common
  • Knee OA
    • Rahimzadeh et al found that prolotherapy decreased WOMAC scores. Note they also found PRP to be superior to prolotherapy [105]
    • 3 Arm study: Dextrose prolotherapy resulted in clinically meaningful sustained improvement of pain, function, and stiffness scores for knee osteoarthritis compared with blinded saline injections and at-home exercises[106]

Surgery

Periarticular Osteotomy

  • Knee Osteoarthritis
    • Osteotomy to correct the mechanical axis of the knee show promise have shown symptomatic improvement extending beyond 10 years[107]

Debridement of Lesions

  • Hip Osteoarthritis
    • Recontour femur has been shown to reduce risk of FAI and modify long-term risk of osteoarthritis[108]

Joint Distraction

  • Knee Osteoarthritis
    • Temporary surgical joint distraction produced symptomatic and structural improvement in end-stage knee osteoarthritis[109]

Cartilage Lesions

  • Autologous Cartilage Transplant
  • Osteochondral Graftin
  • Microfracture

Arthroplasty

  • Definitive Management for patients refractory to conservative management and who are not candidates for less invasive surgery

Rehab and Return to Play

Rehabilitation

  • Physical Therapy Protocols
    • Protocol are joint specific

Return to Play/ Work

  • Limitations are generally based on pain, instability, gait dysfunction, etc
  • Low impact sports and water based sports are generally recommended

Complications and Prognosis

Prognosis

Complications

  • Need for surgery
  • Chronic pain
  • Functional
    • Loss of ADLs
    • Physical inactivity
    • Decreased physical activity
  • Slightly increased risk of
    • Cardiovascular disease[110]
    • Atherosclerotic-related disease[111]
  • Psychiatric
    • Depression due to chronic pain[112]

See Also

References

  1. ↑ Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum 2008;59(9):1207–13
  2. ↑ James, Spencer L., et al. "Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017." The Lancet 392.10159 (2018): 1789-1858.
  3. ↑ Woolf AD, Pfl eger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003; 81: 646–56
  4. ↑ Lawrence RC, Felson DT, Helmick CG, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008;58(1):26–35.
  5. ↑ Oliveria SA, Felson DT, Reed JI, et al. Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis Rheum 1995;38(8):1134–41.
  6. ↑ Hiligsmann M, Cooper C, Arden N, et al. Health economics in the field of osteoarthritis: an expert’s consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum 2013; 43: 303–13.
  7. ↑ Centers for Disease Control and Prevention (CDC): Prevalence of disabilities and associated health conditions among adults—United States, 1999. MMWR Morb Mortal Wkly Rep 2001;50(7):120-125.
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  40. ↑ Wluka AE, Stuckey S, Brand C, et al. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. J Rheumatol 2002;29(12):2585–91.
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  44. ↑ Neogi T, Booth SL, Zhang YQ, et al. Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum 2006;54(4):1255–61.
  45. ↑ Dominick KL, Jordan JM, Renner JB, et al. Relationship of radiographic and clinical variables to pinch and grip strength among individuals with osteoarthritis. Arthritis Rheum 2005;52(5):1424–30.
  46. ↑ Chaisson CE, Zhang Y, Sharma L, et al. Grip strength and the risk of developing radiographic hand osteoarthritis: results from the Framingham Study. Arthritis Rheum 1999;42(1):33–8.
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