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osteoarthritis (OA)

Generally a diagnosis of exclusion. Etiology: 1) primary: unknown 2) hereditary: see Genetics (below) 3) secondary a) cartilage damage - trauma (acute or repetitive) 1] meniscal tear 2] obesity 3] patellar instability may lead to patellofemoral DJD b) abnormal joint alignment 1] congenital dislocation of hip 2] valgus deformity leading to osteoarthritis of the knee d) metabolic 1] hemochromatosis 2] Wilson's disease 3] ochronosis & chondrocalcinosis 4] acromegaly 5] diabetes mellitus 6] hyperparathyroidism e) pseudogout f) Ehlers-Danlos syndrome g) Marfan's syndrome h) joint damage from inflammation or infectious arthritis [3] 4) osteoarthritis is not the consequence of normal use 5) age is most consistent risk factor 6) osteoporosis may confer diminished risk Epidemiology: 1) clinical: > 10% of population > 60 years of age 2) radiographic: a) > 70% of population > 40 years of age b) > 80% of population > 55 years of age c) > 95% of population > 65 years of age 3) women have higher risk for osteoarthritis than men [18] Pathology: 1) loss of cartilage, mensical degradation, formation of osteophytes, subchondral bony sclerosis, subchondral cysts [3] 2) except for erosive osteoarthritis of the hands, DJD is non- inflammatory or minimally inflammatory - low-grade synovitis [3] 3) superficial erosions, hypertrophy, hyperplasia of chondrocytes, depletion of matrix proteoglycan & increased matrix water occur early 4) decreased matrix proteoglycans results from increased proteolytic activity of chondrocytes (cathepsins, elastase, stromelysin, aggrecanase-2 [13]) 5) irreversible damage probably occurs when collagen fibers are degraded 6) cartilage fibrillation & erosion leaving denuded, sclerotic & eburnated bone 7) cartilage damage has already started by the time symptoms are present 8) women sustain greater cartilage loss than do men [18] 9) biomechanical factors play an important role in accelerating joint pathology when structural damage is advanced 10) bone marrow edema plays an important role in accelerating joint pathology [9] Genetics: - point mutation Cys(519) -> Arg in COL2A1 gene encoding subunit for type 2 collagen - mutation in Ank-gene may be involved [4] - HIF2-alpha reactivates genes that are involved in endochondral ossification during childhood initiating a futile attempt to repair cartilage [20] - 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: 1) joint pain & tenderness a) dull b) relieved by rest, worsened by activity c) eventually, pain persists at rest d) little to no pain in non weight-bearing joints 2) brief, localized morning stiffness < 30 minutes 3) joint crepitus, tenderness along joint line 4) loss of range of motion - joint pain on passive range of motion 5) bony enlargement & joint effusions may occur [3] 6) evidence for erosions in typical areas a) 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 [3] b) trapezioscaphoid c) weight-bearing joints (knees, hips, spine) d) first metatarsophalangeal (MTP) joints squaring at the base of the thumb (osteoarthritic bunion) 7) primary osteoarthritis almost never affects: a) the shoulder b) metacarpophalangeal joints c) ulnar side of wrist d) elbow is relatively spared d) ankle is relative spared 8) secondary osteoarthritis involves joints generally not affected by primary arthritis (see etiology) 9) minimal signs of inflammation (heat, redness, pain) except for occasional flares of Heberden's nodes associated with erosive osetoarthritis 10) fatigue contributing to frailty [8] (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 [3] 1) complete blood count (CBC) is normal 2) ESR & serum CRP are normal 3) RF & ANA negative (low titers may occur in elderly) 4) urinalysis is normal 5) synovial fluid analysis a) little or no joint fluid b) non-inflammatory: 200-2000 WBC/mm3 - predominantly monocytes [3] - occasionally up to 3500 WBC/mm3, < 25% neutrophils Radiology: 1) radiographs of joints a) standing views for weight-bearing joints (hip, knee) appropriate to confirm diagnosis [3] b) asymmetric narrowing of joint space* c) subchondral sclerosis, increase in bone density d) osteophyte formation (marginal osteophytes) e) subchondral (juxta-articular) cysts f) syndesmophytes g) eburnation h) no periarticular osteopenia or marginal erosions as seen in rheumatoid arthritis i) > 70% of population > 40 years of age with radiographic evidence of osteoarthrits j) radiographic findings do NOT correlate with symptoms & do NOT assess disease progression k) X-ray findings typical of osteoarthritis do not exclude other diagnoses [3] l) X-rays not necessary to confirm diagnosis of hand osteoarthritis [3] 2) radiographs of spine a) degenerative disk disease with collapse of disks b) degenerative joint disease with facet joint osteophytes c) spondylolisthesis d) kyphosis 3) ultrasonography for diagnosis of popliteal cyst (Baker's cyst) 4) MRI not routinely indicated [3] a) may show bone marrow edema (see pathology) [9] b) minimal or no synovitis [3] c) high resolution MRI & large bore needle arthroscopy are evolving methods for detecting early changes d) 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 [29] e) useful for evaluation of soft tissue pathology such as meniscal tears [3] * distinguishing feature from rheumatoid arthritis Differential diagnosis: 1) chronic monoarthritis a) osteonecrosis b) osteochondritis dissecans c) synovial osteochondromatosis d) pigmented villonodular synovitis e) joint neoplasm f) mechanical disorder g) sarcoidosis h) tuberculosis i) fungal infection 2) chronic polyarthritis a) rheumatoid arthritis (RA) - polyarthritis of proximal interphalangeal joints affects both osteoarthritis & rheumatoid arthritis [3] b) psoriatic arthritis c) sarcoidosis d) systemic lupus erythematosus (SLE) e) gout f) pseudogout - condrocalcinosis & involvement of metacarpophalangeal joints suggest pseudogout 3) other inflammatory disorders a) trochanteric bursitis, anserine bursitis b) de Quervain's tenosynovitis mimicking carpometacarpal OA c) hemochromatosis (especially 2nd & 3rd MCP joints) 4) diffuse idiopathic skeletal hyperostosis (DISH), spondylosis, & ankylosing spondylitis may have similar radiographic features; disk-space narrowing & syndesmophytes favor osteoarthritis 5) other considerations a) radiographic changes in osteoarthritis are common in asymptomatic elderly individuals b) a new onset inflammatory arthritis (i.e. RA, septic arthritis) may be superimposed on pre-existing osteoarthritis c) osteoarthritis of the shoulder, metacarpophalangeal joint, isolated large joints or chondrocalcinosis should prompt investigation for secondary causes Complications: - psychosocial stress & depression common [45] - risk of mortality greater for patients with osteoarthritis of the hip or knee relative to the general population [25] - insomnia from osteoarthritis pain [39] - fatigue is the strongest predictor of reduced activity & frailty* > weight loss, decreased strength, or diminished walking speed [8] Management: 1) pharmacologic agents a) topical agents - capsaisin cream (Zostrix) - methylsalicylate cream - ketoprofen gel - topical diclofenac 1% [19,33] - American College of Rheumatology recommends topical NSAIDs rather than oral NSAIDs for elderly (>= 75 years of age) [35] regardless of whether or not they all doing well on oral NSAIDs [3] - associated with more skin reactions [3] - considerably more expensive than oral NSAIDs [3] - lidocaine patch - glucocorticoids (iontophoresis, phonophoresis) 2) oral analgesics - acetaminophen (not effective) [3,40] - non-steroidal anti-inflammatory agents (NSAIDs); - preferred first line oral agents (< 75 years of age) [3]; - renal, GI & cardiovascular risks [3] - COX-2 inhibitors salsalate, celecoxib for patients with asthma [50] - salicylate - avoid in patients with cardiovascular risk factors; hypertension, hyperlipidemia, renal failure - tramadol (Ultram) (third line) [3] - increased 1 year mortality for use of tramadol in persons >= 50 years with osteoarthritis (RR=2.0) [44] - opiates, when other options exhausted - transdermal fentanyl [17] c) glucocorticoids (pulse dose, i.e. Medrol dose pack) d) injectable agents - intra-articular glucocorticoids (not more frequently than every 6 months) - ketorolac (Toradol) 60 mg IM - canakinumab may diminish proressiom of OA [46] - hyaluronate (Healon, Hyalgan, Hylan G-F): - of no benefit [6]; minimal benefit [11] e) other agents - glucosamine, chondroitin sulfate - of no benefit [21] - see GAIT trial, glucosamine &/or chondrotin - selenium supplements ? [16] - doxycycline [14] - use of beta-blockers is associated with less arthragias & less use of opioids & other analgesics for symptomatic large-joint osteoarthritis [41] - statins may reduce risk of osteoarthritis [54] - antidepressants not effective [47] 2) treatment of depression may improve outcomes [10] - duloxetine (Cymbalta) FDA-approved for treatment of osteoarthritis [22] - beneficial for knee osteoarthritis & hand osteoarthritis [8,48,49] - for use if NSAIDs not effective or contraindicated [3] - not best choice for initial therapy [3] - SNRI of marginal benefit for osteoarthritis [47] 3) orthopedic surgery for intractable pain a) indication based on symptoms & patient preference rather than radiographic severity of osteoarthritis [3] b) 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 [3] c) joint arthroplasty when cartilage destruction is advanced & pain/disability is refractory to conservative therapy d) decompressive laminectomy in patients with spinal stenosis associated with degenerative spondylolisthesis e) chondrocyte/stem cell or osteochondral plug transplantation (experimental) [5] f) ineffective; no better than sham procedure [7] 4) activity a) exercise is 1st line therapy for osteoarthritis [42] b) exercise counseling underutilized [42] c) progressive structured activity for sedentary patients [23,24] d) protect involved weight-bearing joints as needed - cane, crutches, etc. e) weight loss f) physical therapy: - range of motion exercises - strengthening (resistance) exercises - walking may be beneficial in rehabilitation for knee arthritis [8] {30 minutes at least times/week} g) occupational therapy - assistive devices for activities of daily living - bracing/splinting/taping/orthotics - proper footwear 5) other non pharmaceutical measures a) heat/cold modalities b) transcutaneous electrical nerve stimulation (TENs) c) acupuncture may provide short-term benefit [15] d) cognitive behavioral therapy beneficial for patients with osteoarthritis & insomnia [39, 51] 6) patient education a) Arthritis foundation b) reduction of stress on involved joints c) natural history of osteoarthritis not is altered by medication d) 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 7) 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 [28]

Interactions

disease interactions

Related

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

Specific

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

General

arthritis chronic inflammation

Database Correlations

OMIM correlations

References

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