Osteoarthritis is the gradual loss of cartilage, combined with the thickening of the subchondral bone, bony outgrowths at joint margins, and mild, chronic nonspecific synovial inflammation

- The most joint disease, affecting ~50% of those 65 years of age and almost all of those over the age of 75

- Prevalence increases with age

- Affects men and women equally

 Risk Factors:  Obesity (hip and knee), Occupation and Sports (repetitive motion), trauma, genetic factors, osteoporosis

Primary (Idiopathic) --> Localized, one-two sites involved, Generalized affecting three or more sites, erosive arthritis where bone is affected

Secondary (Unknown cause) - Trauma, metabolic, or endocrine disorders, and congenital factors

- Failure of chondrocytes to maintain balance between degradation and synthesis of matrix

- Increased breakdown of cartilage

- Proinflammatory cytokines synthesized by chondrocytes and synviocytes may drive production of cartilage-degrading enzymes

- Mechanical stress contributes significantly to disease initiation and progression

- Rhuematoid is autoimmune in nature with systemic disease, Osteoarthritis is not

- Rheumatoid can have smoking/environment as a RF, Osteoarthritis can have metabolic or mechanical problems

- Rheumatoid is symmetrical, involving small joints; osteoarthritis can be symm. or asym and involve large joints or even the shoulders

- Rheumatoid can be local or systemic inflammation, osteoarthritis is almost entirely local. 

- Rheumatoid has extensive morning stiffness, osteoarthritis does not

- Labs for rheumatoid have elevated ESR, RF present, and leukocytosis in synovial fluid; Osteoarthritis may have mild leukocytosis in synovial fluid

- Synovial membrane is inflamed in Rheumatoid, bones are rubbing together in osteoarthritis

- Knee pain AND

- Radiographic osteophytes AND

- 1 or more of the following: age > 50 years, morning stiffness < 30 minutes, Crepitus on motion

- Pain in the hip AND

-  Two or more of the following:  ESR < 20mm/h, femoral or acetabular osteophytes on radiography, radiographic joint space narrowing

- 1st line for mild-mod. disease

- Mechanism: inhibits synthesis of prostaglandin in CNS, peripherally blocks pain impulse generation

- Dose is 650-1000mg qid (MDD = 4g)

- Consideration: Hepatotoxicity, little effect on platelet function, not at risk for GI bleeding

- Capsaicin, for monotherapy or combo

- Mechanism is it depletes substance P from afferent nociceptive nerve fibers

- Dose: Apply 2-4 times per day to provide adequate pain relief

- Considerations: Local burning, stinging, erythema, keep away from eyes and wash hands after use.

- For patients where APAP is ineffective

- Available OTC or RX

- SE's include GI bleeding, prolonged bleeding, renal insufficiency

- Ceiling effect, dose dependent

- Avoid if patient has: CHF, CKD, HTN, hepatic disease, GI disorders, and the elderly

- GI toxicity and CV risk

- Acute renal insuffiency

- Hypersensitivity

- CNS (dizziness, HA, tinnitus, drowsiness)

- Pregnancy category C/D (3rd trimester)

- Non selective and selective NSAIDS have similar efficacy, celexicob may have fewer side effects

- Black box warning of increased CV events

- In terms of CV risk, it goes Celexicob > Diclofenac > Ibuprofen > Naproxen

- First select patients at low risk of CV events

- use lowest effective dose

- add ASA 81mg and PPI to at-risk patients

- Start with narcotics and non-selective NSAIDS and if those DON'T work, move to semi-selective and then selective.

- Use regular monitoring

- Ibuprofen and ASA --> Ibuprofen may compete at COX-1 enzyme and interefere with ASA's antiplatelet superpowers

- Naproxen - ASA --> Data supports an anti-platelet effect for naproxen similar to that of ASA

- Other non-selective NSAIDS, no data to support this. 

- Patient has no GI or CV risk --> non-selective NSAID OR COX-2 if renal insufficiency

- Patient with increased GI or CV risk (no ASA) --> Choose Cox-2 once daily OR Non-selective NSAID (naproxen preferred) plus PPI

- Patient taking low-dose ASA (with or w/o GI risk) --> COX-2 once daily dose OR Non-selective NSAID (naproxen preferred, never Ibu) with PPI

- Lithium

- Warfarin

- Oral hypoglycemics

- High-dose MTX

- Antihypertensives

- ACEI

- Beta-blockers

- Diuretics

- Fluconazole with Celexicob

- Potential to increase levels of antidepressants (CYP2D6 Suppression)

- Meta-analysis shows effective in reducing pain, improving mobility, and reducing joint-space narrowing

- Mechanism is that it helps prevent breakdown and rebuilds the cartilage

- Dose: 1500mg/day glucosamine, 1200mg/day chondroitin

- Place in therapy not known

- Counsel on herbal products and potential shellfish allergy issue

Intra-articular injections:

- Relief from local inflammation or joint effusion

- After injection minimize stress to joint

- Initial pain relief in 1-3 days

- Should be used infrequently (4-6 month intervals)

Adverse effects:

- Systemic -->  hyperglycemia, edema, inc. BP, dyspepsia, Local effects like joint infection, osteonecrosis, tendon rupture, skin atrophy at injection site. 

**Systemic Corticosteroids NOT recommended in OA**

- Low dose opiods if patient has failed ALL other therapies, usually in combo with APAP, caution in elderly

- Tramadol useful as add-on for those who cannot take NSAIDS, AE's include N/V, dizziness, constipation, HA, somnolence.  Increased risk of serotonin syndrome, counsel on signs and symptoms

- Patient-specific treatment approach

- Education on non-pharmacological therapies

- APAP (<4g/day) is 1st line in combo with topicals

- NSAIDS may be used if APAP ineffective, but look out for renal, GI, or CV problems

- Glucosamine and chondroitin is safe