1. All about Osteoarthritis (in 20 minutes…) Howard Amital, MD, MHA Daniela Amital, MD, MHA Department of Medicine ‘D’ Meir Medical Center, Kfar-Saba “Wear and tear” of the joints

2. Definition n Also known as degenerative joint disease or “wear and tear arthritis”. n Progressive loss of cartilage with remodeling of subchondral bone and progressive deformity of the joint (s). n Cartilage destruction may be a result of a variety of etiologies

3. Prevalence and epidemiology n Over 20 million affected in U.S. n About 60-90% of people over age 65 n Under 45 yrs it is equally common in men and women n Over 55 yrs its more common in women n Nodal OA involving DIP and PIP joints is more common in women and their first degree female relatives

4. Men Age (years) Prevalence of OA (%) Women Age (years) Prevalence of OA (%) Age-Related Prevalence of OA: Changes on X-Ray DIP Knee Hip DIP Knee Hip

5. n Premature OA associated with gene mutations that encode collagen types 2, 9, 10 n OA of knee is more common in African American women n Commonest cause of long-term disability n Large economic impact as a result of medical costs n OA cost the U.S. economy nearly $125 billion per year in direct expenses and lost wages and production.

6. Risk factors n Metabolic (hemachromatosis) n Inflammatory (RA, infection) n age n gender

7. Risk factors n genetic factors n trauma n weight

8. Classification nPrimary nIdopathic nLocalized or generalized nLocal: knee, hip, spine, hands nGeneralized: large joints and spine nSmall peripheral joints and spine nMixed and spine nSecondary nPost-traumataic nCongenital or developmental nLocalized or generalized nCalcium deposition disease nOther: nInflammatory nAvascular necrosis

9. The process – at a cellular level n Cartilage matrix has increased water content and decreased proteoglycan n This is different from the changes that occur with aging  cartilage dries up. n Increased activity of proteinases compared to inhibitors of proteinases. n Breakdown products of cartilage cause inflammatory reaction of synovium n Cytokines cause matrix degeneration. Where do they come from? n  chondrocytes n Cycle of destruction starts n Compensatory bone overgrowth occurs - subchondral bone increases in density

10. Overview of the process n Articular cartilage gets disrupted n Damage progresses deeper to subchondral bone

11. n Fragments of cartilage released into joint n Matrix degenerates n Eventually there is complete loss of cartilage n Bone is exposed

14. What to look for in an x-ray nRadiographic changes visible relatively late in the disease nSubchondral sclerosis nJoint space narrowing esp where there is stress nSubchondral cysts nOsteophytes nBone mineralization should be normal

15. Left: View of normal elbow cartilage through an arthroscope - white, glistening, smooth Right: severe elbow osteoarthritis - cartilage is lost and the bone underneath is exposed

16. n left: Normal x-ray n Right: worn away cartilage reflected by decreased joint space

17. n Joint space narrowing where there is more stress n Subchondral bone has thickened n bony overgrowth

19. significant joint space narrowing as well as proliferative bone formation around the femoral neck (arrows)

20. painful bone on bone contact at the CMC joint and the large bone spurs -- osteophytes.

21. n Are crystals found in osteoarthritic joints? n Yes n Calcium pyrophosphate dihydrate and apatite. n Are of unknown significance and asymptomatic

22. Clinical features and diagnosis nPain Sources –Joint effusion and stretching of the joint capsule –Torn menisci –Inflammation of periarticular bursae –Periarticular muscle spasm –Psychological factors nDeep, aching localized to the joint nSlow in onset nWorsened with activity in initial stages nOccurs at rest with advanced disease

23. Involved joints n DIP, PIP n 1 st carpometacarpal n cervical/lumbar facet joints n 1 st metatarsophalangeal n Hips n Knees n Uncommon n Wrist, elbows, shoulders, ankles

25. n 1 st metatarso-phalangeal most commonly affected in OA of the foot.

26. Typical findings n Heberden’s nodes n Bouchard’s nodes

27. Rt: varus deformity of the knee

28. Treatment nNon-pharmacokinetic nNo proven medication-based disease modifying intervention exists. nAnalgesics (acetominophen) nNSAIDS Help pain symptoms but controversial for long term use in non- inflammatory OA because of risks vs benefits Help pain symptoms but controversial for long term use in non- inflammatory OA because of risks vs benefits nNarcotics nIntra-articular steroids nChondroprotective agents nAnti-depressants nPhysical activity

29. Intra-articular corticosteroids nMay be used if NSAIDS are contraindicated, persistent pain despite use of other medications. n(not > 4 injections per year per joint) n2004 meta-analysis of controlled trials (w/ placebo) showed short term improvement in knee pain, but efficacy in other joints is uncertain. nsaline vs steroid injection? n A study comparing the two in knee OA showed no effect on joint space narrowing or significant difference in pain at the end of the study, but over a 2 yr period saline injections has less pain relief.

30. Intra-articular hyaluronans n Evidence shows they have a small advantage in terms of pain control, compared to intra- articular placebos or NSAIDS. n No evidence for improvement in function n Two studies comparing intra-articular steroids to hyaluronans have come to opposite conclusions- more trials are needed.

31. Surgical: arthroscopy n arthroscopy is not recommended for nonspecific "cleaning of the knee“. n Used to fix specific structural damage on imaging (repairing meniscal tears, removing fragments of torn menisci that are producing symptoms).

32. Joint replacement n If all other rx ineffective, and pain is severe n Loss of joint function n Joints last 8-15 years without complications

33. Fibromyalgia – Are new horizons seen ? OR Fibromyalgia for the psychiatrist Howard Amital, MD, MHA Daniela Amital, MD, MHA Department of Medicine ‘D’ Meir Medical Center, Kfar-Saba

34. n "The Three Graces" by Peter Paul Rubens (1577-1640), Prado, Madrid, Spain.

35. Fibromyalgia - criteria Widespread musculoskeletal pain Widespread musculoskeletal pain Excess tenderness in at least 11 of 18 predefined anatomic Excess tenderness in at least 11 of 18 predefined anatomic

36. Frida Kahlo (1907-1954)

37. Frida used to describe her own paintings as "the most frank expression of myself"

38. The Broken Column

40. Chronic Pain – Defined by Mechanisms nPeripheral (nociceptive) –Primarily due to inflammation or damage in periphery –NSAID, opioid responsive –Behavioral factors minor –Examples  OA  Acute pain models (e.g. third molar, post-surgery)  RA  Cancer pain nCentral (non- nociceptive ) –Primarily due to a central disturbance in pain processing –Tricyclic responsive –Behavioral factors more prominent –Examples  Fibromyalgia  Irritable bowel syndrome  Tension and migraine headache  Interstitial cystitis / vulvodynia, non-cardiac chest pain / etc.  Mixed  Neuropathic

42. Fibromyalgia - some facts 10 times more common in females Studies of humans and of animals have noted that females have a lower pain threshold and tolerance and a higher sensitivity to various noxious stimuli. Pillemer et al. Arthritis Rheum. 1997;40:1928-1939 Prevalence in the community increases with age from 2% at age 20 to 8% at age 70 Prevalence in the community increases with age from 2% at age 20 to 8% at age 70 Most patients present between the ages of 30 and 55 Most patients present between the ages of 30 and 55 Approximately 50% of cases appear after a specific event, most often (physical or emotional trauma) Approximately 50% of cases appear after a specific event, most often (physical or emotional trauma) Wolfe F et al. Arthritis Rheum 1995, 38:19-28.

51. The tender point count functions as a `sedimentation rate' for distress

52. WHAT IS THE ASSOCIATION BETWEEN FM AND PSYCHIATRIC ILLNESS? - Depression n A lifetime history of depression has been reported in 50% to 70% n Current major depression, however, was found in only 18% to 36% Goldenberg DL et al, Arthritis Rheum. 1996;39:1852-1859 Goldenberg DL et al, Arch Intern Med, 1999;159:777-785

53. WHAT IS THE ASSOCIATION BETWEEN FM AND PSYCHIATRIC ILLNESS? - Depression n Similar symptoms: fatigue, sleep disturbances, and cognitive disturbances. n Similar comorbid conditions: migraines, muscular headaches, CFS, IBS, and premenstrual syndrome. n Often improve with antidepressant medications Triadafilopoulos G et al, Dig Dis Sci. 1991;36:59-64.

54. WHAT IS THE ASSOCIATION BETWEEN FM AND PSYCHIATRIC ILLNESS? - other psychiatric disturbances n Dysthymia - 10% Current prevalence (CP) n Panic disorder - lifetime prevalence (LP) -16%, CP- 7% n Phobia LP - 16%, CP -12%. Epstein SA et al. Psychosomatics 1999;40:57-63.

56. The overlapping ill defined disorders FIBROMYALGIA 2 - 4% of population; defined by widespread pain and tenderness EXPOSURE SYNDROMES SYNDROMES e.g. Gulf War Illnesses, silicone breast implants, sick building syndrome CHRONIC FATIGUE SYNDROME SYNDROME 1% of population; fatigue and 4/8 “minor criteria” SOMATOFORM DISORDERS DISORDERS 4% of population; multiple unexplained symptoms - no organic findings MULTIPLE CHEMICAL SENSITIVITY MULTIPLE CHEMICAL SENSITIVITY - symptoms in multiple organ systems in response to multiple substances

58. Rate of fibromyalgia p<0.001 χ 2 =40 (d.f – 2)

59. Distribution of severity of FM p<0.0001 χ 2 =60.5 (d.f – 8) No. of patients

60. Results – average tender point count n Controls – (n=49) 0.18 ±0.4 n PTSD – (n=55) 8.9 ±5.4 n Depression - (n=20) 2.85 ±3 p<0.001, Anova Clinical Global Impression (CGI) PTSD – 5.67 DEPRESSION – 5.65 p=0.62, Anova

70. A Six-month, Double-blind, Placebo-controlled, Durability of Effect Study of Pregabalin for Pain Associated With Fibromyalgia Crofford et al ACR 2006 By the end of the study nearly twice as many placebo patients (61%) had lost therapeutic response compared with pregabalin-treated patients (32%). The most common AEs considered treatment related during OL were dizziness (36%) and somnolence (22%).

72. Thank you for your attention