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Osteoarthritis: Diagnostic Pitfalls & Therapeutic Conundrums PSVMC Medical Grand Rounds June 12, 2012 Richard Wernick, M.D.

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Presentation on theme: "Osteoarthritis: Diagnostic Pitfalls & Therapeutic Conundrums PSVMC Medical Grand Rounds June 12, 2012 Richard Wernick, M.D."— Presentation transcript:

1 Osteoarthritis: Diagnostic Pitfalls & Therapeutic Conundrums PSVMC Medical Grand Rounds June 12, 2012 Richard Wernick, M.D.

2 OA: Background  27 million U.S. adults with clinical OA #1 cause of disability/dysf’n in elderly – 3% of total yrs lived with disability X-ray knee OA in ¼ y/o Sx knee OA in 7% men, 4% women – 1.8 QALYs lost Aging pop, OA   mortality (SMR=1.55) – CV, dementia-related (Neusch ‘11)

3 A Case of Chronic Knee Monoarthritis: Case #11,311 (JZ) 69 y/o male with 2 yrs of insidious & gradually  left knee pain Trouble with stairs, walking  with activity, 30 min MS, no locking PMH – Meniscal tear, scope age 50 – Obesity, MI,  BP, ETOH (5 PBRs/d) Meds – ASA 81, atorvastatin, lisinopril, Ben-Gay PE – bony IPs, knee bulge w/o warmth Work-up?

4 The Case of JZ/Chronic Knee Monoarthritis: What Would You Order? Pick one: 1)AP weight-bearing & lateral knee xr? 2)AP weight-bearing & skyline knee xr? 3)MRI? 4)Arthroscopy? 5)Knee tap for SF analysis? 6)RF  ANA  ESR  CRP? 7)No further tests

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9 OA Dx Pitfall: The Problems with X-ray Nonspecificity with normal aging – X-ray knee OA in 44%  80 y/o, 17% nls >55 – X-ray hand/foot OA in 85% y/o – Spine osteophytes in 90% >50 Insensitivity – Of pts w/chronic knee pain, 38%  xr OA, 49% “pre-radiographic: (cartilage defects on MR, Cibere ’10) Artifactual JSN PPV  severity of jt space  AP knee standing & skyline

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13 Osteoarthritis Dx Pitfall: RA vs OA OARA Presentation Activity  Rest  MS Hand RF X-ray: JSN sclerosis osteophyte Chronic mono, poly    30 mins DIP, PIP + in 15% > 65 Non-uniform + Chronic poly    1 hr PIP, MCP 75% Uniform –

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15 OA Diagnostic Pitfall: Is It Really Even Arthritis? Swelling most specific sign POM,  ROM, tenderness Hip – “troch bursitis”, radiculopathy, meralgia paresthetica Knee – IMD, “anserine bursitis” Spine – nonspecific BP - malignancy, Fx, ID

16 The Case of JZ/Chronic Knee Monoarthritis: What Would You Order? Pick one: 1)AP weight-bearing & lateral knee xr? 2)AP weight-bearing & skyline knee xr? 3)MRI? 4)Arthroscopy? 5)Knee tap for SF analysis? 6)RF  ANA  ESR  CRP? 7)No further tests

17 OA: So How to Diagnose? Clinical picture +/- x-ray Older patient with chronic mono or polyarthritis Insidious pain & stiffness –  with activity,  with rest (non-inflammatory) – Location, location, location

18 A Case of Knee OA (JZ) 69 y/o M with 2 yrs  knee OA Pain Hx MI,  BP, meniscal tear Meds – ASA 81, atorvastatin, lisinopril, Ben-Gay Non-pharmacologic Rx ? (may pick  1) 1) Quad strengthening exercise ? 2) Fitness exercise ? 3)PT – “evaluate & treat” (US, TENS,...) ? 4)A cane ? 5)Patellar taping ? 6)Wedged insole  neoprene sleeve ?

19 Knee OA: Non-Pharmacologic Treatment Quad str if weak – modest benefit – Worse if malaligned? “Land-based” fitness exercise modest US, TENS worthless  BMI not a risk for progression -   minimal  Sx (Niu ‘09) Cane – 1 st RCT 2012  sig  pain (no sham), 2 mos Patellar taping (medially directed) – real or sham Sole/sleeve – little benefit or harm

20 A Case of Knee OA (JZ) 69 y/o M with 2 yrs  knee OA pain Hx MI,  BP, meniscal tear Meds – ASA 81, atorvastatin, lisinopril, Ben-Gay Initial pharmacologic Rx? (pick one) 1)Acetaminophen 2)Salsalate 3)Glucosamine  CS 4)Celecoxib (Celebrex)  PPI 5)Naproxen  PPI

21 Osteoarthritis Treatment: Acetaminophen & NSAIDs Response varies pt-to-pt and not great Acet efficacy for pain – ES 0.21 (Zhang meta ’04) NSAID efficacy for pain – ES 0.23 (Bjordal ’04 meta) – 15% better than placebo after 2-13 wks – 23 RCTs – only 4 independent of industry 13/23 excluded pts not “NSAID-responsive”! NSAIDs of = efficacy, ± > acet – ES (pain) 0.23 vs acet (Zhang ‘04)  risk of PG-inhibitors in elderly Topical NSAID = placebo (Lin ’04) Try to d/c chronic NSAID

22 Acetaminophen: Emerging Issues 2012 FDA – max dose 3, not 4 g/d – 3 g/d  BP 3/2 mm after 2 wks (Sudano, Circulation ‘10) ? Preferential Cox-2 inhibitory activity –  CV risk in epi studies – Will RCTs show  tox to NSAIDs?? (Hinz, Ann Rheum Dis ‘11)

23 So How Efficacious Are NSAIDs/Coxibs for OA (2)? “The current analysis does not support long- term use of NSAIDs for this condition. As serious SE are associated with long-term NSAID, only limited use can be recommended.” Most trials excluded pts with co-morbidity In chronic conditions,  30%  in pain is clinically meaningful – For knee OA, ES of 0.4, 20%  pain Bjordal, BMJ ’04

24 Risks of Prostaglandin-Inhibitors GI ulcer/bleed – RRR with PPI only 40% ARF – Traditional or Cox-2 specific CV events Dose-dependent  in older pts (OA)  if co-morbidity

25 Cardiovascular Risks of NSAIDs Arterial thrombosis Heart failure Atrial fibrillation? Blocking anti-platelet effect of ASA

26 Coxibs Cause MIs Cox-1-sparing Cox-2 inhibitors Rofecoxib (Vioxx) – RR 2-4 in RCTs  withdrawn (as was “Bextra”) High CV risk pts exluded from trials Celecoxib – HR of CV event = 1.8 for 200 mg b.i.d. (Solomon meta ‘08)  even with LD ASA  if higher pre-Rx CV risk – No proven risk for OA low dose 200 mg/d

27 Celecoxib CV Events v. Dose & Baseline Risk Solomon et al. Circulation 2008;117:2104

28 Do “Traditional” NSAIDs Cause MIs? Meta ‘06 (Kearney, BMJ) – RR ibuprofen 1.5, diclofenac 1.6 (vs placebo) MEDAL RCT ‘06: diclofenac = etoricoxib – Diclo relatively Cox-1 sparing Meta ‘11 (Trelle, BMJ) of 31 RCTs – None with prespecified CV endpoint – Traditional NSAIDs associated with stroke, CV death For cohort pts with prior MI, HR = 1.5 for death /MI (Circ ‘11) – Independent of Rx duration – Diclo risk greatest Observational studies residually confounded? Naproxen RR = 1, “PRECISION” RCT in progress

29 Schjerning Olsen A et al. Circulation 2011;123: Incidence of death during treatment with all NSAIDs

30 Mortality Increased if HF Patients on NSAIDs Gislason et al. Increased mortality and cardiovascular morbidity associated with use of NSAIDs in chronic heart failure. Arch Intern Med 2009;169:141-9 Danish cohort study of 35K patients on NSAID after HF discharge HR for death: celecoxib 1.7, ibuprofen 1.3, diclofenac 2.1, naproxen 1.2 (vs. no NSAID)  re-hospitalization for both HF and MI Dose-dependent Avoid NSAIDs in HF

31 CV Risks of NSAIDs: Conclusions & Recommendations Coxibs cause MIs Selective (for Cox-2) NSAIDs may – Avoid diclofenac until safety proven Avoid NSAIDs (PG-I) in arteriopaths – All “elderly” Avoid NSAIDs in pts with HF So, what can we do? – Acetaminophen, ? non-acetylated salicylates, opiates for OA – Prednisone for crystal arthritis

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33 Osteoarthritis Dx Pitfall: Superimposed Crystal Arthritis Both gout & pseudogout more common if OA Beware “OA flares” Gout – IPs, MTP 1, knee – Eccentric sw or yellow skin (IP-tophus) – Tap ! Pseudogout – Knee, wrist, MTP 1 – Tap ! Prednisone vs NSAID vs IA steroid

34 A Case of Knee OA (JZ) “Fails” non-pharm Rx, acet & salsalate Now what? 1)Celebrex 200 mg/d +/- PPI ? 2)Ibuprofen 600 mg t.i.d. +/- PPI ? 3)HC 5/acet 325 q6h prn ? 4)Steroid injection ? 5)Hyaluronan product injection x 3-5 ? 6)Acupuncture ?

35 OA Rx: Opioids? Datapenia 3% abuse behavior in VA Rheum Clinic (Ytterberg ‘98) – In practice? Meta, chronic non-cancer pain, older adults (Papaleontiou, JAGS ‘10) – ES for OA pain 0.46 (n=14 RCTs) – ES fort OA f’n 0.43 (n=9 RCTs) – Constipation 30%, nausea 28%, dizzy 28%, sleepy 21%  if older – Studies short-term, extended-release, hi dose, pretty healthy Acet/HC, LA morphine ?

36 Opiates for OA Were More Toxic Than NSAIDs Solomon DH et al. The comparative safety of analgesics in older adults with arthritis. Arch Intern Med 2010;179: Cohort study of 13K Medicare pts who initiated NSAID or opiate (most screened pts rejected) – 90% OA, mean 80 y/o, 25% on PPI – Matched on propensity scores –  1 yr continuous followup Hazard ratios for opiate vs. NSAID: – MI 2.3, mortality 1.9, hip fx 3.0, falls 1.9, GI bleed 1.1 Unmeasured confounders?

37 Popular OA Treatments No Better than Placebo (!) Glucosamine (meta, Wandell, BMJ ‘10)

38 Glucosamine/Chondroitin for Knee OA: Results Endpt Plac Gluc CS G+CS Cel 20%  pain (1  ) 60% 64% 65% 66% 70%{.008} Pain  (BL230) F’n  (770) {.03} Pt global  (50)  Acet/d #s in ( )=baseline values; { } =p v placebo when <0.05 WOMAC pain scale  500, function 1700, global 100

39 OA Treatments No Better than Placebo (!) Glucosamine Steroid joint injections IA hyaluronic acid Acupuncture – Meta ‘07 (Manheimer, Ann Intern Med)  sham Sham pretty good

40 So, What To Do for OA? 1)Acet 3 g/d 2a)? Non-acetylated salicylate if at risk b)prostaglandin-inhibitor(s) if low risk 3) Opioid - Muscle strengthening -Cane & taping for knee ? -If pt believes, glucosamine? Acupuncture? -Pts will feel better on something that doesn’t work than nothing

41 Osteoarthritis Treatment: Knee Arthroscopy ? > 650K per yr, $5K per Previous uncontrolled trials  pain relief in ½ – But why would it work ? – Placebo effect, regression to the mean ? Moseley ’02 NEJM – DBRCT, n=180 (90% M), <75,  mod knee OA pain on max med Rx – Real vs sham (effectively blinded), 24 mo – Almost as good as sham – Results don’t apply if mechanical Sx present See NEJM 9/11/08 !

42 Arthroscopy Failed for Knee OA Moseley et al. NEJM 2002;347:81

43 Should My Knee OA Patient Be Scoped for a Torn Meniscus? MR meniscal tears in 50% y/o random Framinghites – If chronic sx, 45% y/o v. 26% if not – If significant X-ray OA, 82% had a tear, regardless of sx – 61% with tears were asymptomatic the past month – & ¼ with painful OA have torn ACL (3% controls) So older pts often have epiphenomenal tears on MRI, esp if OA present But... a few will really be c/o sx tears Scope more likely to succeed if... – Sx of locking and  pain – MRI: displaced tear without BM lesions Englund. NEJM 2008;359:1108; Suter. Arthr Care & Res 2009;61:1531

44 Surgical Rx of Hip & Knee OA: Joint Replacements (Older) TJRs still going in  90% at 15 yrs Much better than medical Rx Elective, but some wait too long Deep infection <1%, Sx venous T-E 1-3%, death 0.5% (90d) with TKR Gender and age bias ?

45 Surgical Rx of Hip & Knee OA: Joint Replacements (2) 2012: epidemic of premature failure of metal- metal hips –  1/3 of recent THRs, ? 500K pts – Annual revision rate 4% v. <1% (British Registry) – “metallosis” –  Zero evidence of comparative effectiveness – No new hip/knee ‘03-’07 beat established TJR (Anand, JBJS Am ‘11) – Time to settle for established prostheses?

46 Osteoarthritis: Diagnostic Pitfalls & Therapeutic Conundrums Summary OA Dx is a “clinical” one A “flare” implies a superimposed 2 nd arthritis Medical Rx is not great! Try acetaminophen 1 st Beware all prostaglandin inhibitors in elderly Be cost-effective Pts will feel better if you do something that doesn’t really work than if you do nothing


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