Osteoarthritis

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Osteoarthritis

  1. 1. Osteoarthritis
  2. 2. Osteoarthritis <ul><li>Osteoarthritis is an idiopathic disease </li></ul><ul><li>Characterized by degeneration of articular cartilage </li></ul><ul><li>Leads to fibrillation, fissures, gross ulceration and finally disappearance of the full thickness of articular cartilage </li></ul>
  3. 3. Factors responsible <ul><li>Ageing </li></ul><ul><li>Genetics </li></ul><ul><li>Hormones </li></ul><ul><li>Mechanics </li></ul>
  4. 4. Pathologic lesions <ul><li>Primary lesion appears to occur in cartilage </li></ul><ul><li>Leads to inflammation in synovium </li></ul><ul><li>Changes in subchondral bone, ligaments, capsule, synovial membrane and periarticular muscles </li></ul>
  5. 5. Normal Cartilage <ul><li>Avascular, alymphatic and aneural tissue </li></ul><ul><li>Smooth and resilient </li></ul><ul><li>Allows shearing and compressive forces to be dissipated uniformly across the joint </li></ul>
  6. 6. Structure of Normal Cartilage <ul><li>Chondrocytes are responsible for metabolism of ECM </li></ul><ul><li>They are embedded in ECM and do not touch one another, unlike in other tissues in the body </li></ul><ul><li>Chondrocytes depend on diffusion for nutrients and therefore the thickness of cartilage is limited </li></ul><ul><li>Extracellular matrix is a highly hydrated combination of proteoglycans and non-collagenous proteins immobilized within a type II collagen network that is anchored to bone </li></ul>
  7. 7. Structure of Normal Cartilage <ul><li>Divided into four morphologically distinct zones: </li></ul><ul><li>Superficial : flattened chondrocytes </li></ul><ul><li>high collagen-to-proteoglycan ratio and high water content. </li></ul><ul><li>Collagen fibrils form thin sheet parallel to articular surface giving the superficial zone an extremely high tensile stiffness </li></ul><ul><li>Restricts loss of interstitial fluid, encouraging pressurization of fluid . </li></ul>
  8. 8. Structure of Normal Cartilage <ul><li>Transitional zone: </li></ul><ul><li>Small spherical chondrocytes </li></ul><ul><li>Higher proteoglycan and lower water content than superficial zone </li></ul><ul><li>Collagen fibrils bend to form arcades </li></ul>
  9. 9. Structure of Normal Cartilage <ul><li>Radial Zone: </li></ul><ul><li>Occupies 90% of the column of articular cartilage </li></ul><ul><li>Proteoglycan content highest in upper radial zone </li></ul><ul><li>Collagen oriented perpendicular to subchondral bone providing anchorage to underlying calcified matrix </li></ul><ul><li>Chondrocytes are largest and most synthetically active in this zone </li></ul>
  10. 10. Structure of Normal Cartilage <ul><li>Calcified zone: </li></ul><ul><li>Articular cartilage is attached to the subchondral bone via a thin layer of calcified cartilage </li></ul><ul><li>During injury and OA, the mineralization front advances causing cartilage to thin </li></ul>
  11. 11. Structure of Normal Cartilage
  12. 12. Function of Normal Cartilage <ul><li>Critically dependent on composition of ECM </li></ul><ul><li>Type II (IX&XI) provide 3D fibrous network which immobilizes PG and limits the extent of their hydration </li></ul><ul><li>When cartilage compresses H2O and solutes are expressed until repulsive forces from PGs balance load applied </li></ul>
  13. 13. Function of Normal Cartilage <ul><li>On removing load, PGs rehydrate restoring shape of cartilage </li></ul><ul><li>Loading and unloading important for the exchange of proteins in ECM and thus to chondrocytes </li></ul><ul><li>Chondrocytes continually replace matrix macromolecules lost during normal turnover </li></ul>
  14. 14. OA cartilage <ul><li>The equilibrium between anabolism and catabolism is weighted in favor of degradation </li></ul><ul><li>Disruption of the integrity of the collagen network as occurs early in OA allows hyperhydration and reduces stiffness of cartilage </li></ul>
  15. 15. Degenerative cartilage
  16. 16. Mechanisms responsible for degradation <ul><li>Catabolism of cartilage results in release of breakdown products into synovial fluid which then initiates an inflammatory response by synoviocytes </li></ul><ul><li>These antigenic breakdown products include: chondrointon sulfate, keratan sulfate, PG fragments, type II collagen peptides and chondrocyte membranes </li></ul>
  17. 17. Mechanisms responsible for degradation <ul><li>Activated synovial macrophages then recruit PMNs establishing a synovitis </li></ul><ul><li>They also release cytokines, proteinases and oxygen free radicals (superoxide and nitric oxide) into adjacent and synovial fluid </li></ul><ul><li>These mediators act on chondrocytes and synoviocytes modifying synthesis of PGs, collagen, and hyaluronan as well as promoting release of catabolic mediators </li></ul>
  18. 18. Synovial changes
  19. 19. Cytokines in OA <ul><li>It is believed that cytokines and growth factors play an important role in the pathophysiology of OA </li></ul><ul><li>Proinflammatory cytokines are believed to play a pivotal role in the initiation and development of the disease process </li></ul><ul><li>Antiinflammatory cytokines are found in increased levels in OA synovial fluid </li></ul>
  20. 20. Proinflammatory cytokines <ul><li>TNF- α and IL-1 appear to be the major cytokines involved in OA </li></ul><ul><li>Other cytokines involved in OA are: IL-6, IL-8, leukemic inhibitory factor (LIF), IL-11, IL-17 </li></ul>
  21. 21. TNF- α <ul><li>Formed as propeptide, converted to active form by TACE </li></ul><ul><li>Binds to TNF- α receptor (TNF-R) on cell membranes </li></ul><ul><li>TACE also cleaves receptor to form soluble receptor (TNF-sR) </li></ul><ul><li>At low concentrations TNF-sR seems to stabilize TNF- α but at high concentrations it inhibits activity by competitive binding </li></ul>
  22. 22. IL-1 <ul><li>Formed as inactive precursor, IL-1 β is active form </li></ul><ul><li>Binds to IL-1 receptor (IL-1R), this receptor is increased in OA chondrocytes </li></ul><ul><li>This receptor may be shed from membrane to form IL-1sR enabling it to compete with membrane associated receptors </li></ul>
  23. 23. TNF- α and IL-1 <ul><li>Induce joint articular cells to produce other cytokines such as IL-8, IL-6 </li></ul><ul><li>They stimulate proteases </li></ul><ul><li>They stimulate PGE2 production </li></ul><ul><li>Blocking IL-1 production decreases IL-6 and IL-8 but not TNF- α </li></ul><ul><li>Blocking TNF- α using antibodies decreased production of IL-1, GM-CSF and IL-6 </li></ul>
  24. 24. IL-6 <ul><li>Increases number of inflammatory cells in synovial tissue </li></ul><ul><li>Stimulates proliferation of chondrocytes </li></ul><ul><li>Induces amplification of IL-1 and thereby increases MMP production and inhibits proteoglycan production </li></ul>
  25. 25. IL-8 <ul><li>Chemotactic for PMNs </li></ul><ul><li>Enhances release of TNF- α, IL-1 and IL-6 </li></ul>
  26. 26. Leukemic inhibitory factor (LIF) <ul><li>Enhances IL-1 and IL-8 expression in chondrocytes and TNF- α and IL-1 in synoviocytes </li></ul><ul><li>Regulates the metabolism of connective tissue, induces expression of collagenase and stromolysin </li></ul><ul><li>Stimulates cartilage proteoglycan and NO production </li></ul>
  27. 27. Antiinflammatory cytokines <ul><li>3 are spontaneously made in synovium and cartilage and increased in OA </li></ul><ul><li>IL-4, IL-10, IL-13 </li></ul><ul><li>Likely the body’s attempt to reduce the damage being produced by proinflammatory cytokines, these two processes are not balanced in OA </li></ul>
  28. 28. IL-4 <ul><li>Decreases IL-1 </li></ul><ul><li>Decreases TNF- α </li></ul><ul><li>Decreases MMPs </li></ul><ul><li>Increases IL-Ra (competitive inhibitor of IL-1R) </li></ul><ul><li>Increases TIMP (tissue inhibitor of metalloproteinases) </li></ul><ul><li>Inhibits PGE2 release </li></ul>
  29. 29. IL-1Ra <ul><li>Competitive inhibitor of IL-1R, not a binding protein of IL-1 and it does not stimulate target cells </li></ul><ul><li>Blocks PGE2 synthesis </li></ul><ul><li>Decreases collagenase production </li></ul><ul><li>Decreases cartilage matrix production </li></ul>
  30. 30. IL-10, IL-13 <ul><li>IL-10 decreases TNF- α by increasing TNFsR </li></ul><ul><li>IL-13 inhibits many cytokines, increases production of IL-1Ra and blocks IL-1 production </li></ul>
  31. 31. Osteoarthritis and Joint Replacement <ul><li>Once bone – bone articulation develops, joint replacement ( Arthroplasty) is only viable option. </li></ul><ul><li>Most common in Knees and Hips. </li></ul><ul><li>Very serious surgeries. Often takes months / years to get back to full strength (if ever) </li></ul>
  32. 32. Knee Arthroplasty aka Total Knee Replacement (TKR)
  33. 33. Possible Side Effects of Knee Arthroplasty <ul><li>blood clots in the leg </li></ul><ul><li>blood clots in the lung </li></ul><ul><li>urinary infections or difficulty urinating </li></ul><ul><li>difference in leg length </li></ul><ul><li>stiffness </li></ul><ul><li>loosening of prosthesis </li></ul><ul><li>infection in knee </li></ul>
  34. 34. <ul><li>90% + report increased ROM following surgery </li></ul><ul><li>25% report loosening of prosthesis @ 10 years </li></ul><ul><ul><li>Caused by osteolysis; inflammatory response: reabsorption of bone </li></ul></ul><ul><li>Lots of isometric exercises and walking </li></ul>Knee Arthroplasty
  35. 35. Possible Side Effects of Hip Arthroplasty <ul><li>blood clots in the leg </li></ul><ul><li>blood clots in the lung (1-2% Occurrence) </li></ul><ul><li>urinary infections or difficulty urinating </li></ul><ul><li>difference in leg length </li></ul><ul><li>stiffness </li></ul><ul><li>dislocation of hip </li></ul><ul><li>infection in hip </li></ul>
  36. 36. <ul><li>Dislocation Prevention (2-3% Occurrence) </li></ul><ul><ul><li>using 2-3 pillows between your legs while sleeping and not crossing your legs </li></ul></ul><ul><ul><li>not bending forward 90 degrees </li></ul></ul><ul><li>Exercise </li></ul><ul><ul><li>Lots of isometric exercises will be prescribed to strengthen muscles surrounding joint </li></ul></ul><ul><ul><li>Lots of walking, cycling, swimming, etc. </li></ul></ul><ul><ul><ul><li>Avoid high impact exercises and follow guidelines listed above regarding prevention of dislocation. </li></ul></ul></ul>Hip Arthroplasty
  37. 37. <ul><li>90 – 95% success rate @ 10 years post op. </li></ul><ul><li>Average lifespan 12 – 15 years </li></ul><ul><ul><li>Less if active (IE Younger person) </li></ul></ul><ul><li>Very effective at providing complete pain relief </li></ul><ul><ul><li>Often have to keep person from “over doing it” </li></ul></ul>Hip Arthroplasty
  38. 38. Hip Fractures Usually Occurs @ the “Surgical Neck” of Femur Often results in disruption of blood flow….Avascular Necrosis * *
  39. 39. <ul><li>Usually requires surgery </li></ul><ul><ul><li>THR </li></ul></ul><ul><ul><li>ORIF (Open Reduction, Internal Fixation) </li></ul></ul><ul><ul><ul><li>Uses plates, rods, & screws to fixate femoral fracture </li></ul></ul></ul><ul><li>Post operative Exercise </li></ul><ul><ul><li>Isometrics, ROM exercises </li></ul></ul><ul><ul><li>SLOWLY progress to weight bearing exercises as directed by Physician </li></ul></ul>Treatment of Hip Fracture
  40. 40. <ul><li>One year post mortality is as high as 40% (leading cause of “traumatic death” in elderly) </li></ul><ul><li>Very small percentage regain previous mobility </li></ul><ul><li>20% require nursing home care following fracture </li></ul><ul><li>Often results in accumulation / increase in incidence of other health problem </li></ul><ul><ul><li>CAD, diabetes, stroke, pneumonia,etc… </li></ul></ul>Hip Fractures
  41. 41. Facts about Hip Fractures and Osteoporosis <ul><li>44 million Americans suffer from osteoporosis and/or low BMD </li></ul><ul><li>80% are Women / 20% Men </li></ul><ul><li>Women can lose up to 20 percent of their bone mass in the five to seven years following menopause, making them more susceptible to osteoporosis. </li></ul>
  42. 42. Risk of Hip Fracture and BMD
  43. 43. Facts about hip fractures and Osteoporosis <ul><li>Annual cost associated with osteoporotic fractures is $17 billion in 2001 ($47 million each day). </li></ul><ul><li>One in two women and one in four men over age 50 will have an osteoporosis-related fracture in their lifetime. </li></ul><ul><ul><li>300,000 hip fractures; and approximately  </li></ul></ul><ul><ul><li>700,000 vertebral fractures, </li></ul></ul><ul><ul><li>250,000 wrist fractures; and </li></ul></ul><ul><ul><li>300,000 fractures at other sites. </li></ul></ul><ul><li>MOST ARE PREVENTABLE!!! </li></ul>

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