osteoarthritis (OA)

Introduction

Generally a diagnosis of exclusion.

Etiology

• primary: unknown
• hereditary: see Genetics (below)
• secondary
  • cartilage damage - trauma (acute or repetitive)
    • meniscal tear
    • obesity
    • patellar instability may lead to patellofemoral DJD
  • abnormal joint alignment
    • congenital dislocation of hip
    • valgus deformity leading to osteoarthritis of the knee
  • metabolic
    • hemochromatosis
    • Wilson's disease
    • ochronosis & chondrocalcinosis
    • acromegaly
    • diabetes mellitus
    • hyperparathyroidism
  • pseudogout
  • Ehlers-Danlos syndrome
  • Marfan's syndrome
  • joint damage from inflammation or infectious arthritis
• osteoarthritis is not the consequence of normal use
• age is most consistent risk factor
• osteoporosis may confer diminished risk

Epidemiology

• clinical: > 10% of population > 60 years of age
• radiographic:
  • > 70% of population > 40 years of age
  • > 80% of population > 55 years of age
  • > 95% of population > 65 years of age
• women have higher risk for osteoarthritis than men

Pathology

• loss of cartilage, mensical degradation, formation of osteophytes, subchondral bony sclerosis, subchondral cysts
• except for erosive osteoarthritis of the hands, DJD is non- inflammatory or minimally inflammatory
  • low-grade synovitis
• superficial erosions, hypertrophy, hyperplasia of chondrocytes, depletion of matrix proteoglycan & increased matrix water occur early
• decreased matrix proteoglycans results from increased proteolytic activity of chondrocytes (cathepsins, elastase, stromelysin, aggrecanase-2)
• irreversible damage probably occurs when collagen fibers are degraded
• cartilage fibrillation & erosion leaving denuded, sclerotic & eburnated bone
• cartilage damage has already started by the time symptoms are present
• women sustain greater cartilage loss than do men
• biomechanical factors play an important role in accelerating joint pathology when structural damage is advanced
• bone marrow edema plays an important role in accelerating joint pathology

Genetics

• point mutation Cys(519) -> Arg in COL2A1 gene encoding subunit for type 2 collagen
• mutation in Ank-gene may be involved
• HIF2-alpha reactivates genes that are involved in endochondral ossification during childhood initiating a futile attempt to repair cartilage
• high expression of asporin in osteoarthritic articular cartilage
• susceptibility to osteoarthritis associated with
  • defects in FRZB (type 1)
  • genetic variation in MATN3 (type 2)
  • genetic variation in GDF5 (type 5)
• other implicated genes CHRDL2, ADAM17, ADAMTS4, ADAMTS5, COL2A1

Clinical manifestations

• joint pain & tenderness
  • dull
  • relieved by rest, worsened by activity
  • eventually, pain persists at rest
  • little to no pain in non weight-bearing joints
• brief, localized morning stiffness < 30 minutes
• joint crepitus, tenderness along joint line
• loss of range of motion
  • joint pain on passive range of motion
• bony enlargement & joint effusions may occur
• evidence for erosions in typical areas
  • hands
    • distal interphalangeal (DIP) joints (Heberden's nodes)* pathognomonic for osteoarthritis
    • proximal interphalangeal (PIP) joints (Bouchard's nodes)* pathognomonic for osteoarthritis
    • carpometacarpal (CMC) joints
    • clinical exam more sensitive than radiology
  • trapezioscaphoid
  • weight-bearing joints (knees, hips, spine)
  • first metatarsophalangeal (MTP) joints squaring at the base of the thumb (osteoarthritic bunion)
• primary osteoarthritis almost never affects:
  • the shoulder
  • metacarpophalangeal joints
  • ulnar side of wrist
  • elbow is relatively spared
  • ankle is relative spared
• secondary osteoarthritis involves joints generally not affected by primary arthritis (see etiology)
• minimal signs of inflammation (heat, redness, pain) except for occasional flares of Heberden's nodes associated with erosive osetoarthritis
• fatigue contributing to frailty (see complications)

* stiffness after prolonged period of inactivity

Laboratory

tests for exclusion of other diagnoses unnecessary in the absence of clinical evidence of systemic disease

• complete blood count (CBC) is normal
• ESR & serum CRP are normal
• RF & ANA negative (low titers may occur in elderly)
• urinalysis is normal
• synovial fluid analysis
  • little or no joint fluid
  • non-inflammatory: 200-2000 WBC/mm3
    • predominantly monocytes
    • occasionally up to 3500 WBC/mm3, < 25% neutrophils

Radiology

• radiographs of joints
  • standing views for weight-bearing joints (hip, knee) appropriate to confirm diagnosis
  • asymmetric narrowing of joint space*
  • subchondral sclerosis, increase in bone density
  • osteophyte formation (marginal osteophytes)
  • subchondral (juxta-articular) cysts
  • syndesmophytes
  • eburnation
  • no periarticular osteopenia or marginal erosions as seen in rheumatoid arthritis
  • > 70% of population > 40 years of age with radiographic evidence of osteoarthrits
  • radiographic findings do NOT correlate with symptoms & do NOT assess disease progression
  • X-ray findings typical of osteoarthritis do not exclude other diagnoses
  • X-rays not necessary to confirm diagnosis of hand osteoarthritis
• radiographs of spine
  • degenerative disk disease with collapse of disks
  • degenerative joint disease with facet joint osteophytes
  • spondylolisthesis
  • kyphosis
• ultrasonography for diagnosis of popliteal cyst (Baker's cyst)
• MRI not routinely indicated
  • may show bone marrow edema (see pathology)
  • minimal or no synovitis
  • high resolution MRI & large bore needle arthroscopy are evolving methods for detecting early changes
  • MRI detects structural abnormalities consistent with osteoarthritis of the knee in most older people without radiographic evidence for knee osteoarthritis, regardless of the presence of pain
  • useful for evaluation of soft tissue pathology such as meniscal tears

* distinguishing feature from rheumatoid arthritis

Complications

• psychosocial stress & depression common
• risk of mortality greater for patients with osteoarthritis of the hip or knee relative to the general population
• insomnia from osteoarthritis pain
• fatigue is the strongest predictor of reduced activity & frailty* > weight loss, decreased strength, or diminished walking speed

• disease interaction(s) of osteoarthritis with Parkinson's disease
• disease interaction(s) of osteoarthritis with insomnia

Differential diagnosis

• chronic monoarthritis
  • osteonecrosis
  • osteochondritis dissecans
  • synovial osteochondromatosis
  • pigmented villonodular synovitis
  • joint neoplasm
  • mechanical disorder
  • sarcoidosis
  • tuberculosis
  • fungal infection
• chronic polyarthritis
  • rheumatoid arthritis (RA)
    • polyarthritis of proximal interphalangeal joints affects both osteoarthritis & rheumatoid arthritis
  • psoriatic arthritis
  • sarcoidosis
  • systemic lupus erythematosus (SLE)
  • gout
  • pseudogout
    • condrocalcinosis & involvement of metacarpophalangeal joints suggest pseudogout
• other inflammatory disorders
  • trochanteric bursitis, anserine bursitis
  • de Quervain's tenosynovitis mimicking carpometacarpal OA
  • hemochromatosis (especially 2nd & 3rd MCP joints)
• diffuse idiopathic skeletal hyperostosis (DISH), spondylosis, & ankylosing spondylitis may have similar radiographic features; disk-space narrowing & syndesmophytes favor osteoarthritis
• other considerations
  • radiographic changes in osteoarthritis are common in asymptomatic elderly individuals
  • a new onset inflammatory arthritis (i.e. RA, septic arthritis) may be superimposed on pre-existing osteoarthritis
  • osteoarthritis of the shoulder, metacarpophalangeal joint, isolated large joints or chondrocalcinosis should prompt investigation for secondary causes

Management

• pharmacologic agents
  • topical agents
    • capsaisin cream (Zostrix)
    • methylsalicylate cream
    • ketoprofen gel
    • topical diclofenac 1%
      • American College of Rheumatology recommends topical NSAIDs rather than oral NSAIDs for elderly (>= 75 years of age) regardless of whether or not they all doing well on oral NSAIDs
      • associated with more skin reactions
      • considerably more expensive than oral NSAIDs
    • lidocaine patch
    • glucocorticoids (iontophoresis, phonophoresis)
• oral analgesics
  • acetaminophen (not effective)
  • non-steroidal anti-inflammatory agents (NSAIDs);
    • preferred first line oral agents (< 75 years of age);
    • renal, GI & cardiovascular risks
    • COX-2 inhibitors salsalate, celecoxib for patients with asthma
    • salicylate
    • avoid in patients with cardiovascular risk factors; hypertension, hyperlipidemia, renal failure
    • tramadol (Ultram) (third line)
      • increased 1 year mortality for use of tramadol in persons >= 50 years with osteoarthritis (RR=2.0)
    • opiates, when other options exhausted
      • transdermal fentanyl
  • glucocorticoids (pulse dose, i.e. Medrol dose pack)
  • injectable agents
    • intra-articular glucocorticoids (not more frequently than every 6 months)
    • ketorolac (Toradol) 60 mg IM
    • canakinumab may diminish proressiom of OA
    • hyaluronate (Healon, Hyalgan, Hylan G-F):
      • of no benefit; minimal benefit
  • other agents
    • glucosamine, chondroitin sulfate
      • of no benefit
      • see GAIT trial, glucosamine &/or chondrotin
    • selenium supplements ?
    • doxycycline
    • use of beta-blockers is associated with less arthragias & less use of opioids & other analgesics for symptomatic large-joint osteoarthritis
    • statins may reduce risk of osteoarthritis
    • antidepressants not effective
• treatment of depression may improve outcomes
  • duloxetine (Cymbalta) FDA-approved for treatment of osteoarthritis
    • beneficial for knee osteoarthritis & hand osteoarthritis
      • for use if NSAIDs not effective or contraindicated
      • not best choice for initial therapy
  • SNRI of marginal benefit for osteoarthritis
• orthopedic surgery for intractable pain
  • indication based on symptoms & patient preference rather than radiographic severity of osteoarthritis
  • arthroscopic surgery
    • joint lavage & or debridement
    • meniscal/ligament/tendon repair
    • of benefit only if a loose body or internal derangement is the cause of pain
  • joint arthroplasty when cartilage destruction is advanced & pain/disability is refractory to conservative therapy
  • decompressive laminectomy in patients with spinal stenosis associated with degenerative spondylolisthesis
  • chondrocyte/stem cell or osteochondral plug transplantation (experimental)
  • ineffective; no better than sham procedure
• activity
  • exercise is 1st line therapy for osteoarthritis
  • exercise counseling underutilized
  • progressive structured activity for sedentary patients
  • protect involved weight-bearing joints as needed
    • cane, crutches, etc.
  • weight loss
  • physical therapy:
    • range of motion exercises
    • strengthening (resistance) exercises
    • walking may be beneficial in rehabilitation for knee arthritis {30 minutes at least times/week}
  • occupational therapy
    • assistive devices for activities of daily living
    • bracing/splinting/taping/orthotics
    • proper footwear
• other non pharmaceutical measures
  • heat/cold modalities
  • transcutaneous electrical nerve stimulation (TENs)
  • acupuncture may provide short-term benefit
  • cognitive behavioral therapy beneficial for patients with osteoarthritis & insomnia [39, 51]
• patient education
  • Arthritis foundation
  • reduction of stress on involved joints
  • natural history of osteoarthritis not is altered by medication
  • osteoarthritis by itself does not shorten life expectancy
    • quality of life may be impaired
    • complications of treatment may shorten life expectancy
    • factors associated with arthritis (i.e. obesity) may shorten life expectancy
• investigational
  • adult mesenchymal stem cells (MSCs), which are found in damaged cartilage, can develop into chondrocytes
    • kartogenin promotes differentiation of MSCs into chondrocytes in vitro

More general terms

• arthritis
• chronic inflammation

More specific terms

• Charcot joint; Charcot foot; Charcot arthropathy
• inflammatory erosive osteoarthritis
• nodal osteoarthritis (of the fingers)
• osteoarthritis of the foot
• osteoarthritis of the hand
• osteoarthritis of the hip
• osteoarthritis of the knee
• osteoarthritis of the shoulder
• osteoarthritis of the spine

Additional terms

• Bouchard's node
• cartilage fibrillation
• Heberden's node
• trauma/exercise/surgery & osteoarthritis

Patient information

osteoarthritis patient information

Database

• OMIM: https://mirror.omim.org/entry/140600
• OMIM: https://mirror.omim.org/entry/165720
• OMIM: https://mirror.omim.org/entry/604864
• OMIM: https://mirror.omim.org/entry/612400
• OMIM: https://mirror.omim.org/entry/165720