22 - Osteoarthritis

Question 1

Definition of OA

Answer 1

• ACR (American College of Rheumatology) -> joint pain that occurs for most days of the prior month plus radiographic changes in the symptomatic joint
• Impacts any joint, but typically in spine (cervical or lumbar), hands, hips, and knees

Question 2

Difference between primary and secondary OA

Answer 2

• Primary OA = idiopathic (often in the elderly)
• Secondary OA:
• • Joint insults (trauma, infection)
• • RA, gout
• • Congenital joint abnormalities
• • Hematological genetic abnormalities (leukemia)

Question 3

What protects the joint?

Answer 3

• Synovial fluid -> reduces friction between articulating cartilage surfaces (physical protectant)
• Ligaments & tendons -> via mechanoreceptor sensory afferent nerves fire during movement; allows for the right tension in joints for maximal protection
• Bone -> shock-absorbing effects
• Cartilage:
• • 2-3 mm thin coating of tissue at the ends of 2 opposing bones
• • Lubricated by synovial fluid to create frictionless surface for the opposing bones
• • Compressible characteristics yields impact-absorbing quality

Question 4

Pathophysiology of OA

Answer 4

• Involves a complex interaction of many extracellular and intracellular molecules (metalloproteinases (MMPs), cytokines (IL-1, TNF-alpha), and growth factors)
• Cartilage destruction occurs faster than cartilage formation
• IL-1 and metalloproteases have been found to play an important role in cartilage destruction
• Local growth factors, especially transforming growth factor (TGF) are involved in formation of osteophytes
• • Osteophyte = compensatory mechanism of new bone formation to stabilize the joint
• • Characterized by joint pain, loss of motion, weakness, disability

Question 5

Risk factors for OA

Answer 5

• Ethnicity, age
• Gender and hormonal status
• Bone density, joint injury, joint biomechanics
• Nutritional factors
• Obesity (most modifiable risk factor), occupation
• Physical activity
• Muscle weakness

Question 6

Sx of OA

Answer 6

• Stiffness – morning or after periods of inactivity; lasts less than 30 mins
• Sx localized to affected joint
• Pain worse w/ activity (especially weight bearing) or prolonged use

Question 7

Signs of OA

Answer 7

• Often unilateral, occasionally symmetrical
• Joints not usually tender or inflamed
• Joint instability may be present
• No systemic sx

Question 8

What causes the pain of OA?

Answer 8

• Not related to destruction of cartilage
• From activation of nociceptive nerve endings within the joint by mechanical and chemical irritants
• May be due to distention of synovial capsule by increased joint fluid, microfracture, periosteal irritation, or damage to ligaments, synovium, or the meniscus

Question 9

Diagnosis of OA

Answer 9

• Clinical diagnosis = no further tests if -> > 45 y/o + activity-related joint pain + no morning joint-related stiffness or morning stiffness lasting < 30 mins
• Lab tests useful to rule out other causes of the sx
• Radiographs and joint aspiration (useful for red, hot, swollen joints)

Question 10

Physical exam of OA

Answer 10

• Pain, stiffness, and limitation of both passive and active movement of the joint
• Crepitus (grating, popping of joints), deformity, muscle atrophy, ligament tenderness in 1 or more of the affected joints
• Ligament and capsular laxity (looseness) + muscle atrophy = joint instability (later leading to deformity)

Question 11

X-ray for OA

Answer 11

• Imaging may not directly correlate w/ the clinical picture
• 2017 EULAR recommendations -> X-rays not needed for initial usual presentation of OA or follow-up
• Can help identify narrowing of joint space (due to loss of cartilage), osteophytes, and bone cysts

Question 12

Assessment of severity of OA

Answer 12

• No lab monitoring
• Assessment scales:
• • Western Ontario and McMaster Universities (WOMAC) questionnaire has been widely used to assess pain, stiffness, and physical function in px w/ hip and/or knee OA
• • Visual analog scale (VAS)

Question 13

Goals of therapy for OA

Answer 13

• *Relieve or eliminate pain (and stiffness)
• Improve or restore joint function and mobility
• Improve muscle strength to protect cartilage, ligaments, and joint capsule
• Prevent and reduce damage to the joint cartilage, bone, ligaments, muscles, and nerves
• Maximize QOL
• Educate the pt/caregiver to promote adherence

Question 14

Stepwise approach to OA tx

Answer 14

• Step 1 -> non-pharm (education, exercise, physiotherapy, assistive devices); acetaminophen
• Step 2 -> add topical diclofenac; advise on other topical therapies
• Step 3 -> assess risk of adverse GI events
• • Low (no risk factors) = low dose nonselective NSAIDs
• • Moderate (1-2 risk factors) = low dose nonselective NSAID + gastroprotection OR low dose COX-2 inhibitor
• • High (multiple risk factors) = alternative therapy (ex: local injections, duloxetine, opioids) OR low dose COX-2 inhibitor + gastroprotection
• Step 4 -> if not adequate pain relief, full-dose nonselective NSAID or COX-2 inhibitor +/- gastroprotection

Question 15

Non pharms for hand OA based on ACR 2012 guidelines

Answer 15

• Evaluate ability to perform activities of daily living (ADLs) and provide assist devices
• Instruct in joint protection techniques
• Instruct in use of thermal modalities
• Provide splints for px w/ trapeziometacarpal joint OA

Question 16

Pharm options for hand OA based on ACR 2012 guidelines

Answer 16

• Topical capsaicin, topical NSAIDs
• Oral NSAIDs, including COX-2 selective inhibitors
• Tramadol

Question 17

Non pharms for knee OA based on ACR 2012 guidelines

Answer 17

• Participate in CV (aerobic) and/or resistance land-based exercise
• Participate in aquatic exercise
• Lose weight (for persons who are overweight)

Question 18

Pharm options for knee OA based on ACR 2012 guidelines

Answer 18

• Acetaminophen
• Topical NSAIDs
• Oral NSAIDs
• Tramadol
• IA corticosteroid injections

Question 19

Non pharms for hip OA based on ACR 2012 guidelines

Answer 19

• Participate in CV and/or resistance land-based exercise
• Participate in aquatic exercise
• Lose weight (for persons who are overweight)

Question 20

Pharm options for hip OA based on ACR 2012 guidelines

Answer 20

• Acetaminophen
• IA corticosteroid injections
• Oral NSAIDs
• Tramadol

Question 21

General non-pharms for OA

Answer 21

• Strength training and aerobic exercises (land/aquatic)
• Weight loss of at least 5% in those overweight or obese
• Joint protection (splints, taping, braces)
• Supportive footwear
• Use of ambulation aids (ex: cane, walkers)
• Social support (telephone follow-up, caregiver education)
• Acupuncture
• Heat or cold therapy
• Massage
• Surgery

Question 22

Acetaminophen for OA (dose, role in OA, efficacy, and safety)

Answer 22

• Dose -> 325-1000 mg q4-6h or SR 650 mg q8h x 2 weeks before assessing effect
• • Max 4 g/day
• Role in OA -> 1st line especially for non-inflammatory OA
• Efficacy -> equal to NSAIDs for mild, non-inflammatory OA; less effective than NSAIDs in inflammatory/advanced OA
• Safety -> considered safe; consider 3.2 g/day max in px > 75 y/o; avoid in those w/ > 3-4 drinks/day
• • Enhanced hepatotoxicity w/ other hepatotoxic medications

Question 23

Capsaicin for OA (dose, role in OA, and safety)

Answer 23

• Dose -> apply sparingly TID-QID x 3-4 weeks to achieve maximum therapeutic effect
• Role in OA -> 1st line, especially for non-inflammatory OA
• Safety -> tingling, burning, or redness (majority of px)

Question 24

Topical diclofenac for OA (dose, role in OA, and safety)

Answer 24

• Dose -> OTC up to 2%; Rx up to 10%
• Role in OA -> 2nd line in OA due to safety; can be used first-line if inflammatory component to OA
• Safety -> minimal systemic safety concerns w/ limited systemic BA

Question 25

NSAIDs for OA (dose, role in OA, and safety)

Answer 25

- Dose -> depends on the NSAID - Role in OA -> alternative first line tx for hand OA for those who can’t tolerate local skin reactions or inadequate relief from topical NSAIDs; in knee and hip OA after failure or CI to acetaminophen - Safety: - - Common AE = N, dyspepsia, anorexia, abdominal pain, flatulence & diarrhea in 10-60% of px - - Serious AE = ulcer, GI bleeding, kidney disease, hepatitis, CNS effects, many serious drug interactions

Question 26

NSAID options for those w/ high GI and/or CV risk

Answer 26

- If high GI risk and high CV risk (on ASA) -> avoid NSAID if possible - - If can’t avoid NSAID, if very high CV risk is primary concern -> naproxen + PPI; if very high GI risk is primary concern -> COX-2 + PPI - If high GI risk and low CV risk -> COX-2 alone or traditional NSAIDs + PPI - If low GI risk and high CV risk (on ASA) -> naproxen + PPI - If low GI risk and low CV risk -> traditional NSAID * *High CV risk = CV secondary px w/ ASA or high 10 year CV risk

Question 27

IA steroids for OA (dose, role in OA, efficacy, and safety)

Answer 27

- Dose: - - Methylprednisolone acetate (Depo-Medrol) -> 10-20 mg/joint; 20-80 mg/large joint (knee, hip, shoulder) - - Triamcinolone acetonide (Kenalog) -> 5-15 mg/joint; 10-40 mg/large joint - Role in OA -> alternative first-line tx for both knee and hip OA when pain control w/ acetaminophen or NSAIDs is suboptimal or offered concomitantly w/ oral analgesics - Efficacy -> superior to placebo in alleviating knee pain and stiffness caused by OA but w/ a relatively short duration; benefit lasts 4-6 weeks - Safety -> inexpensive, safe, and effective therapy for individual joints (especially hips/knees) - - AE = hyperglycemia, edema, elevated BP, flushing, dyspepsia

Question 28

IA hyaluronic acids for OA (dose, role in OA, efficacy, and safety)

Answer 28

- Dose -> sodium hyaluronate 1 injection into involved joint; may be given once only, or weekly x 3-5 weeks depending on affected joint & product used - OA role -> 2nd line - Efficacy -> limited efficacy and risks of serious events limit the routine use - Safety -> no general systemic effect - - Serious AE = increased pain, joint swelling, and stiffness

Question 29

Duloxetine for OA (dose, role in OA, efficacy, and safety)

Answer 29

- Dose -> 60 mg once daily (max. dose of 120 mg per day) - OA role -> adjunctive tx in px w/ a partial response to first-line analgesics; may be preferred 2nd line med in px w/ both neuropathic and MSK OA pain - Efficacy -> demonstrated efficacy primarily as add-on therapy when there has been less than optimal response to acetaminophen or oral NSAIDs - - Reduction in pain occurs at about 4 weeks after initiation - Safety -> don’t use w/ potent CYP1A2 inhibitors or MAOI - - Caution w/ other serotonergic drugs (dextro, trazadone, triptans) - - Common AE = GI w/ N, V, constipation - - CI in liver disease, severe renal impairment (ie: CrCl < 30 mL/min)

Question 30

Tramadol for OA (dose, role in OA, efficacy, and safety)

Answer 30

- Dose -> 25 mg AM, titrate dose in 25 mg increments to reach maintenance of 50-100 mg TID (max dose 200-300 mg/day) - OA role: - - Recommended as alternative first-line tx of knee/hip pain in OA in px who have failed tx w/ acetaminophen, topical NSAIDs, and who aren’t appropriate candidates for oral NSAIDs and IA corticosteroids - - Can be safe add-on therapy to partially effective acetaminophen or oral NSAID therapy - Efficacy -> demonstrated efficacy (moderate pain improvement when compared to placebo), primarily as add-on therapy when there has been less than optimal response to acetaminophen or oral NSAIDs - - Reduction in pain occurs at ~4 weeks after initiation - Safety; common AEs = N/V, dizziness, constipation, headache, somnolence - - Don’t use if CrCl < 30 mL/min - - May need to taper dose upon d/c to prevent withdrawal sx

Question 31

NSAID harms

Answer 31

- GI - Renal (ie: AKI) - - Any NSAID better than the others? Not likely - - Increases risk by 1.6-2.2X, depending on volume depletion, CHF, ACEI/ARB use, renal disease, cirrhosis, 70 years and older - Cardiac - - Diclofenac and high-dose celecoxib increase risk by 2-4X - - Low-dose naproxen, ibuprofen, and celecoxib appear CV “neutral” - - Absolute risk depends on other risks (CHF, CAD/ high risk for CVD)

Question 32

Topical therapy for OA (advantage and efficacy)

Answer 32

- Advantage -> major adverse effects comparable to placebo (systemic availability = 2-15% vs. oral NSAIDs) - Efficacy: - - vs. oral NSAIDs for OA of hands and knees is equal - - vs. placebo for OA, tendonitis -> superior in week 1 and 2 but equal after week 4

Question 33

Monitoring drug effect -- what and who/when

Answer 33

- What = decrease in pain - Who/when - - Pt = daily - - HCP = day 7, 14

Question 34

Monitoring pain relief -- what and who/when

Answer 34

- What = improvement or elimination as determined by pre-defined goals - Who/when - - Pt = daily - - HCP = day 3, 7, 14, 28

Question 35

Monitoring N, dyspepsia, abdominal discomfort -- what and who/when

Answer 35

- What = minimal or none - Who/when - - Pt = daily - - HCP = day 3, 7

Question 36

Pt education for OA

Answer 36

- Expected outcomes and response times - Self-monitoring for safety and efficacy - Importance of adherence to non-pharm therapy and pharm therapy - Set goals w/ px (for all types of pain)