Osteoarthritis ac Osteoarthritis is a degenerative joint disease and the most common form of arthritis, affecting over 32.5 million adults in the United States. It occurs when the cartilage that cushions the joints breaks down over time, leading to joint

Degenerative joint disease Osteoarthritis is a degenerative joint disease and the most common form of arthritis, affecting over 32.5 million adults in the United States. It occurs when the cartilage that cushions the joints breaks down over time, leading to joint pain, stiffness, and reduced flexibility. Commonly affected joints include the knees, hips, hands, and spine. Symptoms often worsen with age and can significantly impact daily activities. Treatment options may include lifestyle changes, physical therapy, medications, and in some cases, surgery

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PhitjiraSanguanboonyaphong
Faculty of Pharmaceutical Science
UbonRatchathaniUniversity
OSTEOARTHRITIS
OUTLINES:
•Introduction
•Pathology
•Epidemiology and risk factors
•Clinical presentations
•Diagnosis
•Treatments
INTRODUCTION:
•Osteoarthritis (OA) is a chronic, progressive disorder
characterized by the loss of articular cartilage.
•OA can involves in articular cartilage, synovium,
capsule, and subchondral bone with surrounding
ligaments and muscles.
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Koda-Kimble 10
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PATHOPHYSIOLOGY:
Mechanical stress (ex. obesity, joint trauma)
Chondrocyte induce the production of proteases and
inflammatory cytokines
Localized areas of loss of cartilage increase focal stress
leading to further cartilage loss
Large areas of cartilage loss, bony remodeling and
malalignment develops.
FelsonDT. N EnglJ Med. 2006;354:841 -8.
Samuels J, et al. bulletin of the nyuhospital for joint diseases. 2008;66(3):244-50.
Malalignment increase focal loading, creating a vicious
cycle of joint damage.
EPIDEMIOLOGY & RISK FACTORS:
Nonmodifiable risk factors
-Age
-Sex
-Genetics
-Joint location
Modifiable risk factors
-Obesity
-Physical activity
-Joint injury
Increasedrisk of incidence OA
Hunter DJ, et al. Best practice & Research clinical rheumatology. 2014; 28: 5-15.
EPIDEMIOLOGY & RISK FACTORS:
•Age
1
knee OA
•13.8% (> 25 YO) vs37.4% (≥ 60 YO)
•Sex
2
hand OA
•26% (Female) VS 13% (Male)
•Genetics
1
Heberden’snodes
•10 times more prevalent in female than male
•Obesity
3
knee OA
•30.6% (normal BMI) VS 46.9% (overweight) VS 60.5% (Obese)
•Physical activity and joint trauma
1
•Traumatic injury during sports increase OA risk
•Meniscal damage and knee injury in young persons increase
knee OA in older age.
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2. Hunter DJ, et al. Best practice & Research clinical rheumatology. 2014; 28: 5-15.
3. Jennifer N, et al. PSAP 2014.

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CLASSIFICATION:
•Primary osteoarthritis (Idiopathic)
Localized OA involving one or two joints
Generalized OA involving three or more joints
•Secondary osteoarthritis
The result of an identifiable cause
Joint trauma
Inflammatory arthritis
Jennifer N, et al. PSAP 2014.
CLINICAL PRESENTATION:
•Joint pain and tenderness (asymmetric)
•Stiffness in affected joints
•Limited range of motions
•Instability of weight –bearing joints
•Joint deformity
•Bony outgrowths (osteophytes)
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DIAGNOSIS:
•Medical history and physical examination
1,2
-Joint pain usually related with activity
-Morning stiffness (less than 30 minutes)
-Crepitus sound
-Limited range of motions
•Most frequently involved joints
3
-Knees (41% of affected joints)
-Hands (30%) PIPs, DIPs
-Hips (19%)
1.SinusasK. Am FamPhysician. 2012;85(1):49-56.
2. Lane NE. N EnglJ Med. 2007;357:1413–21.
3. Kenneth D. rheumatology network. Update 30 Oct 2010.
Heberden’snodes
Bouchard’s nodes
DIAGNOSIS (CONT.):
•Laboratory test
-Radiographypresent osteophyte formation, narrow joint
space
1
-Synovial fluid examination
2,3
:
WBC < 1,000 cells/mm
3
Osteoarthritis
WBC > 2,000 cells/mm
3
Inflammatory arthritis
Crystal gout or pseudo gout
1. Lane NE. N EnglJ Med. 2007;357:1413–21.
2. FelsonDT. N EnglJ Med. 2006;354:841 -8.
3. Baker K, et al. Rheumatology network update 2011.
narrow joint space
Osteophyte formation

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TREATMENTS:
•Goal of treatments
Relieve pain and stiffness
Maintain or improve joint mobility
Limit functional impairment
Maintain and improve quality of life (QOL)
TREATMENTS:
•Nonpharmacologic treatments
Patient education
Weight loss at least 4% of body weight
Exercise aquatic exercise, tai chi
Surgery
•Pharmacologic treatments
Topical agents
Oral agents
Injectable agents
Dietary supplements
HoghberMC, et al. Arthritis care &research.2012;64(4):465 –74.
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TOPICAL AGENTS
•Use for acute and chronic pain associated with OA of
superficial joints
•Alternative to oral NSAIDs
•Ex. Diclofenac gel 1% applied QID
Diclofenac solution (1.5%) 40 drops QID
•ADRs:
Local reactions; itching, dry skin, contact dermatitis
TOPICAL NSAIDS:
•MOA: Depletion of substance P (SP).
•SP has been implicated in transmission of pain in arthritis.
•Dose: 0.025% -0.075% capsaicin recommend 4 times/day
•ADRs:
Local reactions such as burning, stinging, erythema
TOPICAL CAPSAICIN:
ORAL AGENTS

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ACETAMINOPHEN:
•Remain the first choicefor mild to moderate OA
•Dose: 325 –650 mg q 4-6 hr (NMT 4 g/day)
•ADR: Hepatotoxicity, Renal toxicity with long term use
•Precautions: chronic alcohol user should be avoid
acetaminophen intake because increases risk of liver
damage and GI bleeding.
•If patient does not have clinical response strongly
recommends the use of NSAIDs
NSAIDS:
•MOA: Blockade of prostaglandin synthesis by inhibiting
cyclooxygenase enzymes (COX-1 and COX-2).
•NSAIDs can divided into2 groups
Traditional NSAIDs
Selective COX-2 inhibitors
•ADRs:
GI: nausea, dyspepsia, abdominal pain, GI ulceration, GI bleeding
Renal: Acute kidney injury
CNS: headache, drowsiness, dizziness
Others: hepatotoxicity, hypersensitivity, platelet dysfunction
Nimesulide Meloxicam Celecoxib
Parecoxib Valdecoxib
Piroxicam Parecoxib Valdecoxib
•NSAIDs induced GI toxicity
Risk factors
oAge > 65 years old
oHigher dose of NSAIDs
oConcurrent taking with corticosteroids or anticoagulants
oHistory of PU or DU
Direct GI Irritation Administering the drugs after meals
PGE
2synthesis inhibition
oCo-therapy with PPIs or double dose of H
2RA or
misoprostol (synthetic PGE
2)
oSubstitution of a COX-2 inhibitor for a traditional NSAIDs
NSAIDS (CONT.):
LanzaFL, et al. Am J Gastroenterol.2009;104:728-38.
•NSAIDs induced nephrotoxicity Acute Kidney Injury
Risk factors
oAge > 60 years old
oU/D renal insufficiency, Heart failure
oConcomitant used with ACEIs and ARBs
oSepsis
Prevention strategy
oUse analgesic with less nephrotoxicity such as
Sulindac (Renal sparing NSAIDs)
NSAIDS (CONT.):
NaughtonCA. Am FamPhysician. 2008;78(6):743-750.
•Efficacy of celecoxib as same as
tNSAIDs.
•GI symptoms and dyspepsia is lower
than tNSAIDs.
•Dose:
Celecoxib 100 mg BID or 200 mg
OD
Etoricoxib 60 –90 mg OD
•ADRs:
Increase cardiovascular risk
Renal toxicity
Hypersensitivity
SELECTIVE COX-2 INHIBITORS:
DeeksJJ, et al. BMJ. 2002; 325: 1-8.

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HOW TO SELECT NSAIDS?: TRAMADOL:
•MOA:
Partial µ opioid agonist and serotonin norepinephrine
reuptake inhibitors
•Dose:
50 –100 mg PO q 4 -6 hr(max 400 mg/day,
≥75 YO max 300 mg/day)
•Dose adjustment:
CrCl< 30 ml/min 50 –100 mg q 12 hours
•ADRs:
Dizziness, headache, nausea, vomiting
•D/I:
SSRI, TCA Serotonin syndrome
OPIOID ANALGESICS:
•MOA: µreceptor agonist
•Recommends for
•Patients whose response to combined nonpharmacologic
and pharmacologic therapy has been less than optimal
•Patient who don’t want surgical intervention
•Ex. Codeine, Morphine
•ADRs: nausea, constipation, somnolence, dry mouth
DULOXETINE:
•MOA:
Selective serotonin norepinephrine reuptake inhibitor
•Dose:
30 -60 mg OD
•ADR:
Headache, somnolence, fatigue, nausea
•D/I:
Substrate of CYP1A2 and 2D6
Moderate inhibitor CYP2D6
DIACEREIN:
•Anthraquinone derivative
•MOA:
Inhibit production and activity of interleukin-1and
secretion of metalloproteinases.
•Dose:
50 mg BID
•ADR:
Rash, diarrhea
INJECTABLE AGENTS

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INTRAARTICULAR CORTICOSTEROIDS:
•MOA: Phospholipase A
2inhibitors.
•Dose:
Triamcinolone acetonide10 –20 mg/dose
Methylprednisolone acetate 20 –40 mg/dose
•ADRs:
Local reactions: infection at the affected joint, tendon
rupture and skin atrophy.t
INTRAARTICULAR HYALURONIC ACID:
•Hyaluronate is a naturally occurring component of the
cartilage and the synovial fluid.
•Act as a lubricant during movement
•Recommend in knee OA
•ADRs:
Pain and swelling at injection site
Pseudoseptic reactions
Hunter DJ. N EnglJ Med. 2015; 372: 1040-7.
DIETARY SUPPLEMENTS
GLUCOSAMINE AND CHONDROITIN:
•Glucosamineis an amino sugar (monosaccharide) and a
prominent precursor in the biochemical synthesis of
glycosaminoglycan and proteoglycan.
•Chondroitinis an important structural component of cartilage
and provides much of its resistance tocompression.
Clegg DO, et al. N EnglJ Med. 2006; 354: 795-808.
TREATMENT RECOMMENDATION OF HAND OA
Is patient ≥ 75 years old?
No Yes
1
st
line
Topical NSAIDs
or
Topical capsaicin
and/or
Tramadol
1
st
line
Oral NSAIDs
Topical NSAIDs
or
Topical capsaicin
and/or
Tramadol
Is treatment effective?
No Yes
Continue
treatment
Combined
therapy with 2
first line agents
TREATMENT RECOMMENDATION OF KNEE
AND HIP OA
Is acetaminophen contraindicated?
No: acetaminophen Yes: Oral/topical NSAIDs
If effective, continue treatment If effective, continue treatment
If ineffective; switch to tramadol
±topical agents
If effective, continue treatmentIf ineffective; switch to opioids,
duloxetine ±topical agents
If effective, continue treatment
If ineffective; switch to an
intraarticular injection
If effective, continue treatment
If ineffective; refer for surgical
consultation

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PHARMACOLOGIC RECOMMENDATION:
Pharmacologic option HandOA Knee OA Hip OA
Topical capsaicin Y N -
Topical NSAIDs Y Y -
Acetaminophen - Y Y
Oral NSAIDs Y Y Y
Duloxetine N Y N
Intraarticular corticosteroids N Y Y
Intraarticularhyaluronic acid N - -
Tramadol Y Y Y
Opioid analgesics N - -
Glucosamine and chondroitin - N N
HoghberMC, et al. Arthritis care &research.2012;64(4):465 –74.
THANK YOU FOR YOUR ATTENTION