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FOCUS 2016

Assessment and Management of Osteoarthritis (OA)

Robert M. Breslow, RPhAssociate Professor

University of Wisconsin-Madison School of Pharmacy

Conflict of Interest Disclosure

I have no healthcare related financial conflicts of interest or relationships to disclose. 

Objectives:  FOCUS 2016Osteoarthritis (OA)

At the conclusion of the presentation, the learner will be able to:

1. Explain the epidemiology and pathophysiology of osteoarthritis.

2. Summarize the main drug and non‐drug therapies for OA, including risks and benefits

3. Explain the association between OA and falls and fall‐related adverse events

4. Design a treatment regimen for mild to moderate OA through the use of mini‐cases

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Mrs. Kneemeier

• 75 yo caucasian woman

• c/o Left knee pain that she rates as 5/10 and right hand pain that affects her daily activities

• “Tylenol does not help me”

• Lives alone in own home

• Does not drink or smoke

• Weight: 160 lbs

• Height: 5’3”

• BMI = 28.3

• Vitals: WNL

Hochberg MC, Altman RD, April KT, et al.. Arthritis Care Res (Hoboken). 2012;64(4):455-474.

Mrs. K’s Medical History and Medications

•Hypothyroidism x 18 years •Hx Heartburn•Hx osteopenia, but no fractures•Medications

• Levothyroxine 100 mcg daily• Acetaminophen 500 mg as needed• Omeprazole OTC 20 mg once daily• Aspirin 81 mg once daily• Calcium with vitamin D, 600 mg calcium/400 units

vitamin D, one daily.

Prevalence and Epidemiology of OA• Most common and costly form of joint disease.  Also called DJD

• Considered a persistent pain disorder

• Joints most commonly affected: knee, hip, 1st CMC, PIP, DIP.  Other joints include shoulder, foot and spine 

• Affects 34% of adults age 65 and older and rises with age

• Lifetime risk (by age 85) of symptomatic knee OA approaches 1 out of 2 

• Lifetime risk (by age 85) for hip OA, 1 out of 4

• Approx. 12% of those over 60 have symptomatic OA of the knee.

• Radiologically confirmed hip OA affects 14% of those over age 85. 

• Radiographic hand OA in 5% of those age 40, but in 65% of those over age 80.

-Dagenais S. Clin Orthop Relat Res. 2009;467(3):623-637.-Feydy A. Radiol Clin North Am. 2009;47(4):723-759.-Osteoarthritis: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and

Health Promotion, Division of Population Health, October 2015

CMC = carpometacarpal;  PIP = Proximal Interphalangeal;  DIP = Distal interphalangeal

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Risk Factors and Contributing Causes

•Age•Female gender

•Obesity•Occupation (wear and tear)•Sports Activities•Prior injury•Muscle weakness

•Propioceptive deficits

-Zhang Y. Clin Geriatr Med. 2010;26(3):355-369.-Bijlsma JW. Lancet. 2011;377(9783):2115-2126.-Murphy L, Helmick CG. Am J Nurs. 2012;112(3 Suppl 1):S13-9.

Pathophysiology of OA• OA is a disease of cartilage (a wear and tear arthritis)

• Adapted to bear and distribute loads. Low metabolic activity, no blood supply or nerves, poor regeneration 

• Loss of proper balance between cartilage formation and destruction.

• Joint space narrowing, splitting/loss of cartilage, exposure of underlying bone, osteophyte formation 

• Underlying bone supports less weight and develops osteophytes.

• OA often initiated by damage to cartilage by physical forces

• Loss of cartilage results in bone on bone

https://stemcelldoc.wordpress.com/2011/11/16/knee-osteoarthritis-grading-limitations-of-x-rays/

Loeser RF. Arthritis Rheum. 2012;64(6):1697-1707.

Common Elements in OA Presentation

•PAIN May arise from subchondral bone, periosteal nerve 

endings, stretching of ligaments, joint inflammation, and muscle spasms. 

• Limited range of motion

•Weakness or instability of weight‐bearing joints

•Decreased physical function•Tenderness, crepitus, and joint enlargement 

• Crepitus is characterized by a peculiar crackling, crinkling, or grating feeling in the joints. 

• Joint deformity (advanced OA)

Hunter DJ Rheum Dis Clin N Am 34 (2008) 623–643

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Assessing OA with the Severity Index 

•Pain or discomfort

•Maximum distance walked

•ADLs

Luquesne, et al. Seminars in Arthritis Rheum. 1991;20 (supple 2): 48-54

Diagnosis of Knee OATraditional clinical criteria

Knee pain plus >3 of the following:Older than 50 years of ageMorning stiffness for less than 30 minutesCrepitus (a grating sound or sensation produced by friction between bone and cartilage)Bony tendernessBony enlargementNo palpable warmth 

These criteria provide a diagnostic sensitivityof 95% and specificity of 69%

www.utdol.com

Sensitivity = True positives; Specificity = True negativesKnee OA Video

Diagnosis of Hand OA: Traditional inclusion criteria

• Hand pain (including hand aching or stiffness) plus >3 of the following four features:– Hard tissue enlargement of 2 or more of 10

selected joints, as follows• 2nd and 3rd PIP’s• 2nd and 3rd DIP’s• 1st CMC’s

– Hard enlargement of two or more DIP joints

– Fewer than three swollen metacarpophalangeal (MCP) joints

– Deformity of at least 1 of the 10 selected joints• Criteria above provide sensitivity and specificity of 94 and 87

percent, respectivelywww.utdol.com

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2 3 45

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Hand OA Bouchard’s and Heberden’s Nodes

Heberden’s Node

Bouchard’s Node

Diagnosis of Hip OA: Traditional Inclusion Criteria 

• Requires presence of hip pain plus >2 of the following three features:– ESR (sedimentation rate) < 20 mm/h– Radiographic osteophytes – Joint space narrowing on radiography – Sensitivity and specificity of 89 and

91 percent, respectively• Without X-ray and laboratory data

specificity is too low (54%)• Diagnosis of hip OA requires lab and

X-ray• Does Mrs. K have hip OA?

Hip OA Video

Why is OA, especially knee OA, associated with increased falls risk?

• Lower limb weakness

• Slower gait

• Decreased mobility

• Pain

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Controversy Over OA and Falls Risk• Some studies suggest that OA is protective• Some studies make the case for OA as a risk factor for

falls– The presence of any arthritis or joint pain has been reported to

be a risk factor for falls

– OA has a higher mean relative risk of predicting future falls than age or cognitive status

• Any joint: RR = 2.4

• Hip: RR = 1.7

• Limited evidence for a causal link between hip OA and/or knee OA and future risk of falling and fractures

• Joint replacement appears to increase the risk of falls-Arnold and Gyurcsik. Physiotherapy Canada. 2012;64(3):302-314-Vennu and Bindawas. Clin Interv Aging. 2014;9:793-800-Tsonga, et al. Clin Orthop Surg. 2015;7(4):449-456-Ng and Tan. Age Ageing. 2013;42(5):561-566-Nevitt, et al. Arthritis Care Res. 2016;68(8):1089-1097

Impact of the cycle of falls leading to fractures and resulting in a fear of falling

• Decreased functional activity• Decreased recreational activity• Decreased quality of life• Increased disability• Increased costs

Overall OA Treatment Goals 

• Achieve a healthy lifestyle– Educate the patient about his/her role in managing OA

• Improve quality of life

• Pain control

• Improve joint function/minimize disability

• Prevent progression

• Maintain normal body weight

-NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on Health: Osteoarthritis. April 2015

-UpToDate. Nonpharmacologic therapy of osteoarthritis. 2014

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Overview of the Treatment of OA

• Non‐pharmacologic

– Exercise

• Strengthening, aerobic conditioning, range of motion

– Weight control

– Decrease stress on joints

– Nondrug pain relief techniques

– Alternative therapies

– Surgery

• Pharmacologic

– Medications to control pain 

Non‐pharmacologic Tx

2012 American College of Rheumatology (ACR) Non‐Pharmacologic Recommendations

JOINT STRONG RECOMMENDATIONS CONDITIONAL RECOMMENDATIONS

KNEE OA

‐Cardiovascular (aerobic) and/or resistance    land‐based exercise‐Aquatic exercise‐Weight loss for persons overweight

‐Self‐management programs‐Manual therapy in combination with supervised exercise‐Psychosocial interventions‐Medially directed patellar taping‐Wedged insoles as determined appropriate‐Instructed in use of thermal agents‐Walking aids, as needed‐Tai Chi for knee OA only‐Chinese acupuncture‐Instructed in use of TENS

HIP OA

‐Cardiovascular (aerobic) and/or resistance    land‐based exercise‐Aquatic exercise‐Weight loss for persons who are overweight

‐Self‐management programs‐Manual therapy in combination with supervised exercise‐Psychosocial interventions‐Instructed in use of thermal agents‐Waling aids, as needed

HAND OA

No strong recommendations    were made. The evidence supporting these interventions demonstrated only a small to moderate effect size

‐Evaluate the ability to perform ADLs‐Instruct in joint protection techniques‐Assistive devices, as needed, to help with ADLs‐Instruct in use of thermal modalities‐Provide splints for patients with trapeziometacarpal joint OA

Hochberg MC, Altman RD, April KT, et al. Arthritis Care Res. 2012;64(4):455-474.

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Joint Protection• Move around (avoid one position for extended periods)• Good body mechanics• Good posture• Proper body weight• Splints or braces to support the joint• Maintain muscle strength• Avoid repetitive hand activities (hand OA)• Reduce pressure on joints• Pacing of activities• Proper balance between activity and rest• Respect for pain• Distribute weight over non-involved joints• Use assistive devices• Avoid positions of deformity

The CDC Arthritis Self-Management Program

1. techniques to deal with problems such as pain, fatigue, frustration and isolation

2. appropriate exercise for maintaining and improving strength, flexibility, and endurance

3. appropriate use of medications,

4. communicating effectively with family, friends, and health professionals

5. healthy eating

6. making informed treatment decisions

7. disease related problem solving

8. getting a good night's sleep.

Tai Chi

• A 12‐week single‐blinded randomized, controlled trial of Tai Chi in subjects with symptomatic knee OA 

• Subjects (40) were randomized to receive 60 min of Tai Chi vs nutrition education and stretching exercises (the attention control group) 2x/wk

• TheTai Chi group had greater improvements in WOMAC pain scores 

WOMAC = Western Ontario and McMaster Universities Arthritis Index (WOMAC)

TAI CHI FOR ARTHRITIS‐GROUP

TAI CHI FOR ARTHRITIS‐SOLO

Hawker GA. Osteoarthritis year 2010 in review: non-pharmacologic therapy. Osteoarthritis and Cartilage. 2011;19:366e374

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Knee only OA without co-morbidities

Knee only OA with co-morbidities

Multi-joint OA without co-morbidities

Multi-joint OA without co-morbidities

Biomechanical interventionsWalking caneIntra-articular corticosteroidsTopical NSAIDs

Oral COX-2 inhibitors(selective NSAIDs)Intra-articular corticosteroidsOral Non-selective NSAIDsDuloxetineBiomechanical interventionsAcetaminophen

BalneotherapyBiomechanical interventionsIntra-articular corticosteroidsOral COX-2 inhibitors(selective NSAIDs)Duloxetine

Biomechanical interventionsIntra-articular corticosteroidsTopical NSAIDsWalking CaneOral COX-2 inhibitors(selective NSAIDs)CapsaicinOral Non-selective NSAIDsDuloxetineAcetaminophen

Core TreatmentsAppropriate for all patients

Land-based exercise Water-based exerciseWeight management Self-mgmt educationStrength training

OARSI Guidelines for the Non-surgical Management of Knee OA(Osteoarthritis Research Society International)

McAlindon TE, et al. Osteoarthritis and Cartilage. 2014;22: 363-388

Recommended treatmentsAppropriate for the following types

Pharmacologic Tx

American College of Rheumatology Conditional Pharmacologic Recommendations(No strong recommendations were made for hand, knee or hip OA)

Intervention Hand Knee Hip

Acetaminophen ─ √ √

Oral NSAIDs √ √ √

Topical NSAIDs** √  √ No Rec.

Tramadol √ √ √

Intra‐articular Corticosteroid Inj. No √ √

Chondroitin sulfate ─ No No

Glucosamine ─ No No

Topical capsaicin √ No ─

Intra‐articular hyaluronate Inj No No Rec No Rec

Duloxetine ─ No Rec No Rec

Opioid analgesics No No Rec No Rec

** Use topical first before oral in persons age 75 and older

American College of Rheumatology, 2012 Recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the Hand, Hip and Knee. 2012

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Is there a role for opioids?

• From the American Journal of Medicine, 2013– “Older adult patients who have cardiovascular disease,

diabetes, or those who take low-dose aspirin should be taking opioid therapy instead of NSAID therapy for chronic pain” De Leon-Casasola, OA. Am J Med. 2013;126 (3 suppl 1):S3-S11.

• American Geriatrics Society– Opioids are a viable option for patients at higher risk for

NSAID-related adverse effects

For specific drugs and doses, please refer to accompanying table

Acetaminophen

• Useful for mild pain. NOT an anti-inflammatory

• First line therapy for OA of hip and knee

• Maximum dose 4g/day (alone or with combo products)• Routine use of 4g/day may be associated with liver toxicity

• Increase in ALT 3x ULN

• Leading cause of acute liver failure in the US

• Some manufacturers are recommending 3g/d maximum)• Consider only 2 gms per day for chronic use in the elderly

• Increased risk w/alcohol

• The combination of acetaminophen + NSAID has not been proven safe

• Regular use of both increases the risk for renal toxicity.

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Efficacy of Acetaminophen

• Overall, inferior to NSAIDs for OA pain, but less GI adverse effects

• Lancet study in 2016 concluded no role for acetaminophen irrespective of dose (da Costa, et al. Lancet. 2016;387:2093-105)

• Best results when scheduled as compared to prn

Mrs. K

•Did she “fail” acetaminophen?

•How would you determine this?

•Does she need a different drug?

•How would you discuss this with her?

Nonsteroidal anti‐inflammatory drugs NSAIDs)

• Low dose NSAID for appropriate individuals if acetaminophen unsuccessful

• Increase dose of NSAID as necessary• Ceiling effect

• Analgesic effects immediate

• Anti-inflammatory effect delayed (1-2 weeks)

• Does not prevent joint damage

• Pharmacokinetics• Highly protein bound• Elimination half-lives differ among NSAIDS

www.utdol.com

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Selection of NSAIDS

• Cost and co‐pay (formulary) considerations

• Topical vs oral (risk vs. benefit)

• Elimination half‐life and dosing schedule (adherence)

• SAFETY

• Efficacy among NSAIDS can vary with individual patient• No NSAID proven superior to other NSAIDs• If poor response to one NSAID, a fair trial with another NSAID is appropriate.  Be aware of safety profiles. 

• Celecoxib is NO MORE EFFECTIVE than other NSAID’s

• Lowest effective dose, shortest duration possible

• Use of PPI, H2 blocker or misoprostol to lessen GI adverse effects in selected patients

Topical NSAIDs

• Similar in efficacy to oral NSAIDs for knee or hand OA (pain, function, and stiffness)

• Much lower systemic exposure = lower incidence of serious adverse events, GI or CV or other systemic adverse events

• ACR recommends as alternative first line drug for knee OA

• Available as gel, drops, or patch

• Downside: application hassle; local adverse effects; costly

• Some evidence that efficacy is limited to 4 weeks of use

• For use on hands, wrists, elbows, knees, ankles, or feet.

• NOT for hip OA

Note:  Topical salicylates (for example, Aspercreme, not generally effective for OA and not    compared to NSAIDs

Diclofenac Topical Product Options

(Dosing is not equivalent)

•Diclofenac Gel 1% •Diclofenac Gel 3% (NOT FOR OA)•Diclofenac Patch 1.3%•Diclofenac Solution 1.5% and 2%

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NSAIDs: Overview of toxicity

• 10‐20% of patients treated with NSAIDs experience abdominal pain, dyspepsia, nausea

• 15‐30% of NSAID users develop endoscopically confirmed ulcers.

• Cardiovascular risk (esp. COX‐2 inhibitors)

• Renal insufficiency 

• 16,000 deaths per year in US, most from GI events

• Symptoms do not necessarily correlate with lesions and do not reliably precede a catastrophic GI Event

• Risk for serious GI effects goes up with ulcer hx, multiple NSAIDs, high dose, increasing age, use of corticosteroids, anticoagulant use

Paola Patrignani. Managing the Adverse Effects of Nonsteroidal Anti-inflammatory Drugs. Expert Rev Clin Pharmacol. 2011;4(5):605-621

Degree of Inhibition of COX-2 Relative to COX-1

NSAID COX-2 SELECTIVITY

Etodolac 23

Meloxicam 11

Celecoxib 9

Diclofenac 4

Sulindac 3

Piroxicam 2

Ibuprofen 0.4

Naproxen 0.3

Indomethacin 0.2

Ketorolac 0.003

38Wright JM. CMAJ. 2002;167(10):1131-1137

Combination NSAID + GI Protectant to reduce GI risk• Naproxen/esomeprazole combination (Vimovo®)

• Approved OA, RA, and ankylosing spondylitis, and to decrease the 

risk for NSAID‐associated gastric ulcers.

• Diclofenac/misoprostol [(50/200) (Arthrotec®)]or 

[(75/200) (Arthrotec 75®)] • for OA, RA in patients at high risk of developing NSAID‐induced gastric and duodenal ulcers and their complications.

• WARNING: Avoid use/handling by women who could be pregnant 

due to risk of fetal abortion

• Ibuprofen/famotidine (Duexis®) 800/26.6  three times daily

• Approved for OA, RA, & to reduce risk for gastric and duodenal 

ulcers in patients at risk for NSAID‐associated ulcers.

ALL the above have same GI warnings as other NSAIDs

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Celecoxib (COX‐2 Selective): GI toxicity

Significantly fewer GI symptoms of dyspepsia, nausea, diarrhea, and abdominal pain with celecoxib

A systematic review of eight studies on COX-2 inhibitors showed 58% reduced risk for ulcer complications for celecoxib vs nonselective NSAIDs

Aspirin NEGATES the GI benefit

Long term GI safety superiority not shown

The greater the selectivity for COX-2, the lower the risk of GI complications. Antman EM, Circulation 2007;115:1634 –1642

Take‐home Messages about  GI Risk of NSAIDS 

– Use of ANY NSAID increases risk of GI adverse events• Consider risk vs. benefit for each patient

– Use lowest dose, for shortest period – Watch for signs of GI bleeding (rectum, emesis)– Try other approved therapies BEFORE oral NSAIDs– Use of celecoxib can reduce GI risk in those NOT taking aspirin (no renal advantage over non‐selective NSAIDs)

– Concurrent use of misoprostol or PPI or H2 blocker can be  protective

– Celecoxib PLUS a PPI sometimes needed and can work

Cardiovascular Events from NSAIDs • COX‐2 vs. placebo

– MI:  RR = 1.86 

• Non‐Selective vs. Placebo

• Nonselective NSAID vs COX‐2• Naproxen:  RR 0.64 for vascular event• Any non‐naproxen NSAID (primarily diclofenac or ibuprofen): RR 1.14

• Elevated CV risk is greatest soon after acute MI

NSAID Type of Study Outcome (event) RR

Naproxen Meta‐analysis of RCTsMeta‐analysis of OSs

VascularCV, mostly MI

0.920.97

Ibuprofen Meta‐analysis of RCTsMeta‐analysis of OSsRegistryRegistry

VascularCV, Mostly MIRecurrent MIMortality

1.511.071.251.50

Diclofenac Meta‐analysis of RCTsMeta‐analysis of OSsRegistryRegistry

VascularCV, Mostly MIRecurrent MIMortality

1.631.401.542.40

Antman EM, Circulation 2007;115:1634 –1642.

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Recommendations on the use of NSAIDs with regard to CV risk

• The greater the affinity for COX‐2, the greater the CV risk.

• Can increase risk of adverse CV events unrelated to their effect on ASA

• Risk of recurrent MI in patients with CAD, and increase risk of death in those with preexisting CV disease such as unstable angina

• Avoid use in patients during the perioperative period after CABG

• Can increase blood pressure (worsen control)

• Can exacerbate/worsen heart failure.

• Non‐selective NSAIDs such as ibuprofen and naproxen can attenuate aspirin’s beneficial antiplatelet effect.  Avoid if possible.  FDA alert

• In patients using NSAIDs on an occasional short‐term basis, aspirin should be taken 2hr prior to NSAID. 

• Even short term use (within first week after MI) can increase risk of recurrent MI/death. 

-Friedewald V, et al. Am J Cardiol. 2010 Sep 15;106(6):873-84. -Antman EM, Circulation 2007;115:1634 –1642 -UpToDate, 2012

A suggested algorithm for use of long‐term NSAID therapy and gastroprotective agents according to GI and CV Risk

Patient requires NSAID therapyPatient requires NSAID therapy

High GI RiskHigh GI Risk

High CV Risk (on ASA)

High CV Risk (on ASA)

Avoid NSAID if possible 

Avoid NSAID if possible 

High CV Risk(On ASA)NSAID 

unavoidable

High CV Risk(On ASA)NSAID 

unavoidable

Naproxen + PPI if CV risk is primary 

or low dose celecoxib + PPI if GI is primary

Naproxen + PPI if CV risk is primary 

or low dose celecoxib + PPI if GI is primary

Low CV RiskLow CV Risk

Celecoxib ± PPI or 

traditional NSAID + PPI

Celecoxib ± PPI or 

traditional NSAID + PPI

Low GI RiskLow 

GI Risk

High CV Risk (on ASA)

High CV Risk (on ASA)

Naproxen + PPI or low 

dose celecoxib*#

Naproxen + PPI or low 

dose celecoxib*#

High CV RiskHigh CV Risk

Naproxen + PPI

Naproxen + PPI

Low CV RiskLow CV Risk

Any non‐specific 

(traditional) NSAID

Any non‐specific 

(traditional) NSAID

Low dose celecoxib = 200 mg once daily

*Gastroprotection with a PPI may be indicated#Addition of celecoxib attenuates the CV protective effect of ASA

Scarpignato C, et al. BMC Medicine. 2015;13:55Rostrom, et al. Aliment Pharmacol Ther. 2009;29(5):481

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Renal Effects of NSAIDs

• High risk patients include those with CHF, renal dx, elderly, diuretic use, volume depletion, cirrhosis

• These clinical situations result in renal vasoconstriction and concomitant NSAID use blocks compensatory renal vasodilation leading to worsening renal dysfunction.

• Fluid and electrolyte disturbances• Potassium elevations – esp with K+ sparing diuretics and

ACE-Is• Sodium and water retention

• May interfere with treatment for hypertension

• Cox-2 inhibitors NOT any safer than ns-NSAIDs

Other ADRs of NSAIDs

• Central Nervous System

• Headache (rare)

• Dizziness (indomethacin, others)

• May cause confusion in the elderly

• Hepatic Effects

• Sulindac and diclofenac most commonly linked, but all NSAIDs pose risk.

• Allergic Reactions

• Bronchospasms to ASA, others

• Urticarial Reactions

• Rash

• COX-2

• Contraindicated in sulfa allergy

• Interactions with other medications that increase bleeding risk

Our patient,  Mrs. K

• If she DID fail acetaminophen, would you recommend an NSAID? Why or why not?

• Where does she fall on the algorithm?

• What risk factors does she have for NSAID-induced toxicity?

• How would you give her a trial of an NSAID?

• Would a topical NSAID be a good idea?

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Treatment Modalities for Knee and Hip OA

• Acetaminophen• Topical NSAIDs• Joint aspiration followed by glucocorticoid injection can

relieve pain –best pain relief seen in the first 2-4 weeks

• Tramadol can be useful• µ-opioid receptor agonist, weak serotonin and NE reuptake

inhibitor, modest analgesic effects• Can be used as add-on with acetaminophen or NSAID• nausea, vomiting, dizziness, constipation, headache, and

somnolence• Potential interaction with other serotonin mediating drugs• Adjust dose for renal dysfunction

• Oral NSAIDs (if less than age 75 or low CV and GI risk)

Hochberg MC, Altman RD, April KT, et al. Arthritis Care Res (Hoboken). 2012;64(4):455-474.

Second Line Agents for Knee and Hip OA

• Opioid analgesics

- Reasonable choice for patients for whom all other treatment options have failed and who are at high surgical risk (thus no joint arthroplasty)

- Monitor for adverse events: nausea, vomiting, constipation, somnolence, dry mouth, falls resp. depression, addiction

• Surgery

• Duloxetine (see next slide)

• Intra-articular hyaluronate (knee only)

• Generally once weekly for 3 to 5 weeks.

• Benefit has been debated

Hochberg MC, Altman RD, April KT, et al. Arthritis Care Res (Hoboken). 2012;64(4):455-474.

Second Line:  Duloxetine

• Primarily as add-on therapy when there has been less than optimal response to acetaminophen or NSAIDs

• Adverse events: nausea, vomiting and constipation, fatigue, somnolence and dizziness

• Has approved indication for musculoskeletal pain, including osteoarthritis

• Better evidence for knee• Can increase falls risk• Avoid in severe renal impairment (crcl < 30 mLs/min)• Gradual dose reduction when discontinuing• Monitor for orthostatic hypotension • Dose: 30 mg up to 60 mg per day• Studied only up to 4 months of use

(Frakes et al. Curr Med Res Opin. 2011;27(12):2361-72)

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Treatment Recommendations for Hand OA

• First line for patients less than age 75• Oral NSAIDs (if low CV and GI risk) (add PPI if chronic therapy)• Topical NSAIDs• Topical capsaicin• Tramadol (add on or monotherapy)

• Combination of 2‐first line if monotherapy less than effective (oral and topical NSAIDS should not be used together)

• First line for patients age 75 and older• Topical NSAIDs• Topical capsaicin• Tramadol as add on or monotherapy

• Combination of 2‐first line if monotherapy less than effective (oral and topical NSAIDs should not be used together

Hochberg MC, Altman RD, April KT, et al. Arthritis Care Res (Hoboken). 2012;64(4):455-474.

Other treatments that have not achieved sustained support by clinical trials and are 

currently not recommended

• Glucosamine/chondroitin–disappointing overall performance, not recommended

by ACR and not recommended by OARSI

• Acupuncture–little evidence, not recommended by ACR except for

the patient with substantial discomfort who has failed all other therapies and is not a surgical candidate.

Hochberg MC, Altman RD, April KT, et al. Arthritis Care Res (Hoboken). 2012;64(4):455-474.

McAlindon TE, et al. Osteoarthritis and Cartilage. 2014;22: 363-388

Capsaicin (substance P)

• Full dose topical capsaicin cream (0.025% and 0.075%)

• Applied 3-4 times/day to the affected area/joint• Relief in 14 days up to 4-6 weeks• Counseling needed for application techniques and

cautions• Avoid eye area• High drop out rate due to burning sensation, but burning

feeling gets better with time

• Only recommended by ACR for hand OA

Hochberg MC, Altman RD, April KT, et al. Arthritis Care Res (Hoboken). 2012;64(4):455-474.

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How did Mrs. K do?

• She had failed acetaminophen, had very bothersome knee OA

• She was reluctant to start on topical NSAID because of the application effort required

• She started on celecoxib, but it did not help her pain much

• Tried naproxen (she’s on a PPI)

• This worked well, but she is concerned about the risks

• Finally tried the diclofenac drops

• Worked well, got tired of applying, switched to patch (Flector)

• She DID lose weight and now has BMI of 24, doing Tai Chi

• Easier for her to do her gardening and shopping

The Chronic Osteoarthritis Management Initiative of the U.S. Bone and Joint Initiative

• Non‐Pharmacologic• Education and self‐management

• Low impact exercise and weight loss

• Walking aids/assistive devices

• Alternative and complementary approaches• No consensus on acupuncture, thermal modalities, or TENS

• Surgical interventions• Joint replacement (hip and knee)

Nelson AE, et al. Seminars in Arthritis Rheum. 2014

The Chronic Osteoarthritis Management Initiative of the U.S. Bone and Joint Initiative

• Pharmacologic (in order of recommendation)• Acetaminophen as first line (broad consensus)

• Topical NSAIDs or capsaicin• Oral NSAIDs (often with gastroprotection)• Intra‐articular corticosteroids for hip and knee OA• Tramadol for refractory pain

• Possibly opioids (last resort if other analgesics don’t work )• Possibly duloxetine for comorbid depression and pain

Nelson AE, et al. Seminars in Arthritis Rheum. 2014

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Additional Reminders/Strategies

• Try acetaminophen first, up to 4 grams per day in divided doses for pain

• Limit the duration of the 4 gram per day dosing

• May need to try more than one NSAID for pain• Important differences between non-specific and COX-2 specific

NSAIDs and among non-specific NSAIDs

• Avoid long term use, if possible

• Assess for CV, GI, and renal risk and tailor therapy

• Assess for drug-disease interactions

• Monitor renal and hepatic function (creatinine and transaminases)

• Topical NSAID may be safer for use in elderly

American Academy of Orthopedic Surgeons. Treatment of osteoarthritis of the knee. Evidence based guideline. 2013.

Clinical Performance Measures for Orthopedic Surgeons and Physicians

• Assessment for use of anti-inflammatory or analgesic OTCs

• GI prophylaxis

• Function and pain assessment

• NSAID risk assessment

• Physical exam of the involved joint/joints

• Anti-inflammatory/analgesic therapy

• Therapeutic exercise for the involved joint

American Academy of Orthopedic Surgeons/Physician Consortium for Performance Improvement. Osteoarthritis Physician Performance Measurement Set. 2006

Case  1Mr. Jones, age 72, presents to his primary care provider with a complaint of progressively worsening pain in both knees.  His knees are stiff for about 20 minutes when he arises in the morning and for a few minutes after getting up from a chair during the day.  He has some difficulty walking because of the pain.  Pain is exacerbated with kneeling, squatting, or climbing stairs.  Sitting or resting relieved the pain.  He reported that he would rate his worst pain 6/10.  He noticed a grating sound when he bends his knees.  He sometimes felt that his knees might give out and this caused him to limit his activities.  His ROM was affected by joint stiffness.  He has resisted using medications to relieve his pain.   

Mr. Jones is overweight.  He has a history of high blood pressure, type 2 DM,  and a distant past of peptic ulcer disease.  He does note intermittent GERD. 

Current medications include:  Lisinopril 10 mg once daily, ASA 81 mg once daily, Metformin 500 mg twice daily.

What would you recommend for Mr. Jones’ management?

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Case 2Mrs. Bouchard is an 84 yo female residing in an assisted living facility.  You notice that she is having increasing difficulty arising from a sitting position and is noted to grimace when she attempts to stand.  She reports to you that her hands are stiff and that every morning when she gets up her knees feel stiff for about 15 minutes.  She also reports knee tenderness.  She has a longstanding history of hip arthritis diagnosed about 6 years ago for which she has received conservative management with mild pain relievers.  Unfortunately, the pain relievers don’t seem to be helping her hand and knee pain.  Recently, she has been declining opportunities for group outings because of her pain and stiffness.  

Mrs. B’s medical problems include high blood pressure, a past MI, and has experienced 1 or 2 TIAs, and has atrial fibrillation.  

Medications include:  Atenolol 50 mg daily, ASA 81 mg daily, enalapril10 mg daily, hydrochlorothiazide 25 mg daily,  warfarin 2.5 mg daily, and acetaminophen 500 mg twice daily.

What are your recommendations for management?

Conclusion

• Establish evidence‐based and patient appropriate treatment goals and determine whether treatment goals (efficacy and tolerability) are being met through patient and provider monitoring/ surveillance.  This could include the use of screening tools. 

• If goals are not met, the ineffective medication should be tapered and discontinued, a new medication and/or alternative therapy can be introduced, and/or physical and occupational therapy could be modified (combining non‐pharm and pharmacologic approaches)

• Educate older patients about safety and efficacy of cognitive behavioral and movement‐based therapies and identify local practitioners or agencies that provide them

• Management commonly involves a multidisciplinary approach and may require regular reinforcement and modification