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A. Epidemiology navigator

  1. OA also called degenerative joint disease (DJD)
    1. Unclear if OA is a single disease or multiple disorders
    2. Similar final common pathway with cartilage loss
    3. Result is bone-on-bone in joint, causing pain and reduced motion
    4. Joint effusion is not a prominent part of OA
  2. Most common form of arthritis
    1. Pain worse on use of joints
    2. Not a primary inflammatory arthritis
  3. Prevalence in persons >30 years in USA
    1. Symptomatic knee OA 6% (>12 million cases in USA)
    2. Symptomatic hip OA 3% (>6 million cases in USA)
    3. Overall, ~20-30 million persons in USA have OA
  4. Incidence increases with age, and most cases occur in older persons [3]
    1. Incidence increases markedly with age >40-45
    2. Incidence of knee OA is ~900 per 100,000 person-years in age >70
    3. Incidence of hip OA is 400-500 per 100,000 person-years in age >70
    4. Knee OA more common in women
    5. Hip OA slightly more common in men
    6. Nearly 200,000 total hip replacements / year in USA
  5. Occurs frequently in families (usually polyarticular)
    1. Typically with Heberden's and Bouchard's nodes
    2. Possible localization with chromosome 7
    3. Polygenic autosomal recessive trait in most families
  6. May occur in association with diffuse idiopathic skeletal hyperostosis (DISH)

B. Causes [4]navigator

  1. Classification
    1. Primary (idiopathic): no clear cause; variety of risk factors
    2. Secondary (systemic or localized)
  2. Risks for Primary Hip (Knee) OA
    1. Old age
    2. High bone mass
    3. Increased body mass index (BMI) / obesity
    4. Participation in weight-bearing and/or high-impact sports such as elite running
    5. Occupations with prolonged standing
    6. Joint malalignment
  3. Joint Malalignment
    1. Congenital or traumatic deformity may be underlying cause
    2. Primary quadriceps muscle weakness may enhance joint malalignment
    3. In another study, greater quadriceps strength at baseline increased likelihood of tibiofemoral OA progression in malaligned and lax knees [6]
    4. Obesity is a major contributing factor, especially to knee OA, probably deforming joint
    5. Varus or valgus deformity >5 degrees in both knees is associated with 3-5X increased risk for developing OA [22]
    6. Left untreated, unicompartmental OA develops in ~55% of malaligned limbs over 10-20 years [1]
  4. Joint (Space) Alterations
    1. May predispose to OA
    2. Trauma is very common in history of patients, particularly those with knee OA
    3. Knee joint injury in young adults is a risk factor for later osteoarthritis [16]
    4. Quadriceps muscle weakness is a contributing factor to developing knee OA
    5. Loss of knee joint space (called joint space narrowing) normally occurs with aging
    6. Knee joint space narrowing 0.12-0.62 (mean 0.30mm/year) has been documented [22]
    7. Increased joint space narrowing is associated with development of knee OA [22]
  5. Secondary Causes
    1. May be underlying in young and very elderly patients with OA
    2. Avascular Necrosis - sickle cell disease, HbSC disease, glucocorticoid use (see below)
    3. Inflammation - infection, spondyloarthropathy
    4. Crystal Disease - especially pseudogout (CPPD), less often gout
    5. Wilson's Disease
    6. Hemochromatosis - usually involves the metacarpalphalangeal joints
    7. Acromegaly
    8. Neuropathy - Charcot Joint ("Debris, Disarray, Destruction, Normal Mineralization")
    9. Tabes Dorsalis
    10. Developmental deformities, acetabular dysplasia, osteonecrosis, joint arthritis
    11. Known Malalignment
  6. Young persons with OA should be evaluated for secondary causes

C. Pathophysiologynavigator

  1. Biologic and genetic contributions are likely important in development of OA
    1. Genetic contributions to ~50% of hand and hip OA, less to knee OA
    2. Collagen metabolism at the condrocyte level is probably important in OA development
    3. Bone marrow edema is associated with rapid progression of knee OA [27]
  2. OA as a Systemic Disorder [21]
    1. Substantial changes in many mesenchymal tissues beyond bone are present in OA
    2. Abnormal lipid metabolism
    3. Stromal cell differentiation abnormalities
    4. Neuroendocrine factors including leptin may be involved
    5. Obese persons are at increased risk for OA; their leptin levels are elevated
    6. Progression of OA (not incidence) is associated with low vitamin D levels
  3. Some inverse relationship between OA and osteoporosis
  4. Mechanisms of Cartilage Destruction [7]
    1. Poorly understood
    2. Degeneration of the cartilage extracellular matrix (ECM) exceeds new synthesis
    3. Main components of ECM are Type II collagen and aggrecan
    4. Physical (OA) or cytokine (inflammatory arthritis) mediated aggrecan cleavage occurs
    5. Aggrecan can be cleaved by several enzymes including ADAMTS 1, 4 and 5
    6. ADAMTS 5 appears to be the major enzyme involved in pathological cleavage (in animals)
    7. Proteinases including metalloproteinases are involved as well

D. Physical Examination navigator

  1. Hands
    1. Distal (DIP) and Proximal Interphalangeal (PIP) Joints
    2. Thumb - carpometacarpal (CMC) involvement
    3. Sparing of metacarpalphalangeal (MCP) joints
  2. Bouchard's (PIP) and Heberden's (DIP) Nodes common
  3. Knee > Hip = Neck (Cervical Spine) disease quite common
  4. Ankle or Shoulder disease should prompt investigation for secondary causes
  5. Joint Effusions
    1. OA is mechanical problem but joint effusions do occur, particularly in knee
    2. Effusions typically mild, rarely warm, erythema absent
    3. Joint fluid in DJD usually has <2000 cells, mainly non-hematic and/or lymphocytes
    4. Joint fluid tends to be highly viscous in DJD
    5. Contrast with free-flowing fluid in inflammatory arthritis

E. Laboratory navigator

  1. Development of serum markers for OA progression is underway
  2. Inflammatory markers (ESR, CRP) are normal or only slightly elevated
  3. Radiographic Evaluation
    1. Plain radiographs may be obtained if diagnosis is questionable
    2. Joint space narrowing is the most common finding
    3. Periarticular bony sclerosis occurs earlier (reaction to cartilage breakdown)
    4. Osteophyte formation in later disease, usually with severe DJD
    5. Very poor correlation between radiographic appearance of joint and symptoms or disability
  4. Bone marrow lesions (representing edema) on magnetic resonance images correlate well with pain [20]
  5. Pathology
    1. Focal areas of damage to articular (cartilagenous) surface
    2. New bone growth in periarticular areas (called osteophytes)
    3. Changes in subchondral bone
    4. Mild synovitis with upregulated inflammatory proteins
    5. Thickened joint capsule

F. Differential Diagnosis Hip Pain [2] navigator

  1. OA
  2. Trochanteric Bursitis
  3. Meralgia Paresthetica (lateral femoral cutanoues nerve entrapment)
  4. Lumbar Radiculopathy
  5. Lumbar Spinal Stenosis
  6. Chronic Inflammatory Arthritis
    1. Rheumatoid Arthritis
    2. Spondyloarthropathies
  7. Osteonecrosis
  8. Iliotibial Band Syndrome
  9. Metastatic Cancer of the Femur
  10. Gout or Pseudogout

G. Nonpharmacologic Therapy [3,4,12]navigator

  1. Exercise
    1. Aerobic and resistance exercise each improve symptoms in knee and hip OA patients
    2. Six minute walking distance, pain scores, quality of life were improved
    3. Radiographic appearance did not change in education only versus exercise groups
    4. Routine exercising is strongly recommended for knee and hip OA patients
  2. Physical Therapy (PT)
    1. Manual physical therapy affected joints has been used
    2. Combined with range of motion, strengthening, and cardiovascular exercises
    3. When combined with exercise, PT reduces pain and increases walking distance
    4. PT + exercise together may delay or alleviate the need for surgery
  3. Joint Unloading
    1. Cane or crutch
    2. Weight loss
  4. Realignment
    1. Braces and patellar taping
    2. Shoe inserts
  5. Acupuncture for Knee OA [31]
    1. Compared with sham acupuncture and education
    2. Some benefits on pain, functionality, patient global assessment by 26 weeks
    3. conflicting efficacy for pain component [11,15]
    4. Consider as adjuvant therapy in moderate to severe knee OA or other forms of OA

H. Medical Treatment [3,4,18] navigator

  1. Overview
    1. No disease modifying agents for osteoarthritis (DMOADS) have been developed to date
    2. Initial goals are to reduce pain and return patient to activity
    3. Acetaminophen and/or NSAIDs are usually first line for pain
    4. Exercise and physical therapy may delay progression and/or need for joint replacement
    5. Tramadol (Ultram®) may also be used for chronic pain relief
    6. Glucocorticoid and/or hyaluronin injections may be temporarily effective
    7. Cartilage implants or autologous chondrocyte transplants have been developed
    8. Joint replacement is frequently required as disease progresses
  2. Acetaminophen (Tylenol®)
    1. High dose acetaminophen (1gm qid) is reasonable first line therapy [2]
    2. Less gastrointestinal upset and renal problems with acetaminophen compared to NSAIDs
    3. However, most patients do not receive adequate relief with acetaminophen alone
    4. Liver function must be monitored with long term acetaminophen
    5. Caution with alcohol consumption during high dose acetaminophen use
  3. Long Acting NSAIDs
    1. Often far more effective for pain control compared to acetaminophen
    2. COX-2 selective or NSAIDs+proton pump inhibitor (PPI) preferred for long term therapy
    3. Thus, celecoxib (Celebrex®) should be considered
    4. Rofeccoxib (Vioxx®) has been withdrawn due to increased cardiovascular risk [32,33]
    5. Switching to COX-2 selective NSAIDs will prevent most GI ulceration and reduces the need for adjunctive GI medications in osteoarthritis [28]
    6. COX-2 biased oxaprozin (Daypro®) and nabumetone (Relafen®) may also be used
    7. Long term therapy with nonspecific NSAIDs often requires gastrointestinal (GI) ulcer prophylaxis [2]
    8. Because most OA patients are typically older, must carefully monitor of GI and renal side effects; PPI should generally be added in older patients with OA [2]
    9. COX-2 selective inhibitors have renal effects but minimal GI effects
    10. In patients at very high GI bleeding risk, COX2 inhibitor + PPI essentially no GI bleeding
  4. Nutritional Supplements
    1. S-Adenosylmethionine (SAM)
    2. Glucosamine
    3. Chondroitin Sulfate
  5. S-Adenosylmethionine (SAM) [17]
    1. Cofactor for many enzymes
    2. Doses 600-1200mg/d used in studies mainly <1 month
    3. Apparently as effective as NSAIDs in reducing pain and functional limitation
    4. Fewer adverse effects than NSAIDs (but probably similar to acetaminophen)
    5. May be considered as an alternative (or add on) therapy in OA
  6. Glucosamine Sulfate [14,19,23]
    1. Glucosamine is a normal constituent of glycosaminoglycans (GAGs)
    2. GAGs are normally found in cartilage matrix and synovial fluid
    3. Glucosamine is well tolerated and had some effect in some studies
    4. Glucosamine sulfate 1500mg qd for 3 years prevented joint space narrowing [19]
    5. Glucosamine improves symptomatic disease in some studies[14,19]
    6. In two randomized blinded trials, glucosamine had no effect on symptoms in knee OA [5,8]
    7. Glucosamine + chondroitin significantly reduced pain in knee OA patients with moderate to severe pain at baseline but not in overall population [2,8]
    8. Glucosamine sulfate 1500mg po qd x 2 years no better than placebo in hip OA [35]
    9. Glucosamine 400mg + chondroitin 300mg + primorine 425mg (Relamine®) pharmaceutical grade available by prescription for OA
    10. Quality and reproducibility of glucosamine preparations are highly variable [23]
    11. Chondroitin alone has no clear benefit on symptoms or progression in OA [26]
    12. Consider glucosamine + chondroitin in knee OA with moderate to severe pain [8]
  7. Other Non-Invasive Treatments
    1. Local topical creams - capsaicin and diclofenac topicals
    2. Capsaicin 0.025% (Zostrix®, Heet®) applied tid-qid provides modest pain relief
    3. Diclofenac (Voltaren® Gel 1%) 2-4gm qid applied locally provides modest pain relief [36]
    4. Physical Therapy for strengthening musculature is very important
    5. Ultrasound therapy may alleviate some of the pain
    6. Oral chondroitin appears to have modest efficacy with few side effects [14]
    7. Tramadol (serotonin/opiate agonist) is a non-addictive, moderately potent pain medication that is generally well tolerated; dose is 50-100mg po q6-8 hours
    8. Opiates should be avoided if possible since conditions are chronic
    9. Estrogen replacement therapy (ERT) may reduce risk and progression of OA
    10. Neck braces are often quite helpful with cervical spine disease
  8. Leech Therapy [29]
    1. Leech saliva contains many anti-thrombotic and anti-inflammatory agents
    2. Leeches have been used to treat pain conditions in the past
    3. Four to 6 locally applied leeches to the knee in patients with OA of the knee and pain
    4. Leeches left in place until they detach themselves (mean 70 minutes)
    5. Control group was locally applied diclofenac (gel) twice daily, days 0-28
    6. On day 7, pain reduced in leaches by 60% versus 20% reduction with diclofenac
    7. Pain scores were no longer different after day 7
    8. Total symptoms, stiffness, and function all significantly better with leeches at day 28
    9. Leech therapy is effective and safe for treatment of knee pain due to OA

I. Injections [34]navigator

  1. Local Glucocorticoid Injection
    1. OA is primarily a mechanical problem with accompanying inflammation
    2. Joint effusions occur commonly in moderate and severe OA
    3. Effusions often have low grade chronic inflammation (usually 200-1500 cells/µL)
    4. Consider as adjunct to acetaminophen and NSAIDs and/or after fluid drainage
    5. Gluoroscopic-guided intra-articular bipuvicaine + triamcinolone hexacetonide 40mg more effective for pain reduction at 2 months (3 needed to treat) than bipuvicaine alone []
    6. Very inexpensive drug cost per injection (less than $2.00) [34]
  2. Glucocorticoid Injetions for Knee OA [34]
    1. Many (~30-40%) patients with knee OA will benefit from glucocorticoid injection
    2. Effects usually persist for at least 1 month
    3. Injection of glucocorticoids into knees every 3 months for two years did not accelerate cartilage loss and should be considered safe [9,34]
    4. Methylprednisolone (Depo-Medrol®) 20-80mg/injection
    5. Triamcinolone acetonide (Kenalog®) 20-80mg/injection
    6. Triamcinolone diacetate (Aristocort Forte®) 20-80mg/injeciton
    7. Triamcinolone hexacetonide (Aristospan Intra-articular®) 20-40mg/injection
  3. Hyaluronate Injections[10,30,34]
    1. Hyaluronate is major component of normal synovial fluid
    2. These agents are designed to improve the viscoelastic properties of synovial fluid
    3. May also stimulate endogenous hyaluronate production
    4. Highest molecular weight preparations are probably most effective [30]
    5. Some improvement in joint pain and motion over placebo following injection into knee
    6. Pain, inflammation, and swelling at site of injection may occur
    7. Anaphylactic reactions have been reported in a few patients
    8. About as effective as naproxen in decreasing pain
    9. Expensive ($120-230 per injection) compared with glucocorticoids
    10. Hylan G-F 20 (Synvisc®) is a cross-linked derivative of hyaluronic acid
    11. Hyalgan® 20mg/2mL injection per week for 3-5 weeks
    12. Synvisc® 16mg/2mL injection per week x 3 weeks
    13. Euflexxa® 20mg/2mL injection per week x 3 weeks
    14. Orthovisc® 30mg/2mL injection per week x 3-4 weeks
    15. Supartz® 25mg/2.5mL injeciton per week x 3-5 weeks

J. Surgical Treatments [18]navigator

  1. Arthroscopic Knee Surgery
    1. Of no or little benefit in typical knee OA [25]
    2. Some role for younger persons with acute symptoms not relieved with medications
    3. Debridement may relieve source of acute mechanical dysfunction
  2. Joint Replacement
    1. Moderate or severe OA are often indications for joint replacement
    2. Knee replacement is very effective
    3. Unicompartmental knee arthroplasty increasing
    4. Hip replacements are usually effective but have longer recovery period
    5. About 200,000 total hip replacements / year in USA
    6. Shoulder replacments usually done primarily for pain control
    7. Shoulder replacement prostheses have poor range of motion
    8. Hip or knee replacement must include prophylaxis against venous thromboembolism
  3. Total Knee Replacement (Arthroplasty) [1]
    1. Very effective with good ROM and pain relief results in most patients
    2. Gold standard treatment for recalcitrant knee OA
    3. Recommended for patients with advanced OA of knee involving any of 3 compartments
    4. For debilitating arthritis or failure to respond to other interventions
    5. Hospitalization is typically ~3-4 days for most patients
    6. Crutches or walker for first 6 weeks, then cane for ~6 weeks while strength recovers
    7. Physical therapy is critical to recovery
    8. Replacements usually last >10-15 years (90% at >10 years)
    9. Venous thromboembolism is most common complication (<8%)
    10. Infection or aseptic loosing occurs in very small number of patients
  4. Deep Cartilage Defects in Knee
    1. Very common problem with severe pain and premature osteoarthritis
    2. Engineered autologous chondrocyte transplants show promise in repairing defects
    3. Primarily useful for single defects
    4. Undifferentiated mesenchymal cells (localized defects <2cm in diameter)
  5. Grafts
    1. Osteochondral autografts - good five year results
    2. Osteochondral allografts - food 2-5 year results

References navigator

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