Osteoarthritis

Clinical Snapshot

Osteoarthritis (OA) is the most common joint disease worldwide and a leading cause of chronic pain and disability, most often affecting the knees, hips, hands, and spinal facet joints.^[1] Despite being commonly described as "wear and tear," OA is not a passive degenerative process — it involves active biochemical and low-grade inflammatory change throughout the whole joint organ, including the articular cartilage, subchondral bone, synovium, and the supporting ligaments and muscle. Primary OA is idiopathic and age-related, and is the far more common form seen in practice; secondary OA results from an identifiable prior insult to the joint — trauma, malalignment, infection, or an underlying inflammatory, metabolic, or congenital joint disorder. For an individual patient, pain and functional loss often remain stable for long stretches, but a higher body mass index, a greater number of comorbidities, and lower baseline function each predict a higher chance of symptomatic worsening over time — findings a pharmacist can use to set realistic expectations with a patient at diagnosis.

Recognize the Condition

Typical presentation

Joint pain that is worse with activity and improves with rest, morning stiffness that resolves in under 30 minutes (in contrast to the prolonged, often hour-plus morning stiffness of inflammatory arthritis), and a gradual, insidious onset over months to years rather than an acute one. Crepitus (a grating or crackling sensation with joint movement), bony enlargement, reduced active and passive range of motion, and — in later stages — visible deformity, joint instability, and muscle atrophy around the affected joint are common examination findings.

Presentation by joint — where the treatment approach differs

Knee OA

The most common site of symptomatic OA. Pain is typically worse with stairs, kneeling, and prolonged standing or walking. Knee malalignment — genu valgum ("knock knee") or genu varum (bow-leg) — is an independent risk factor for developing and progressing knee OA. Weight-bearing x-rays (including a flexed patellofemoral view) are needed to properly assess joint space narrowing. Both topical and oral pharmacotherapy, and intra-articular injection, are well studied for this joint.

Hip OA

Pain is classically felt in the groin and may radiate to the anterior thigh, buttock, or knee — a patient reporting only knee pain occasionally has referred hip pathology, so examine the hip when knee findings do not explain the symptoms. Topical therapy is not effective for hip OA because the joint sits too deep for meaningful drug penetration through the skin — oral and injectable options apply instead.

Hand OA

Most frequently affects the distal and proximal interphalangeal joints (producing the bony nodules known as Heberden's and Bouchard's nodes, respectively) and the first carpometacarpal (thumb base) joint. Topical NSAID is the preferred initial pharmacologic option; topical capsaicin is not recommended for hand OA because of the risk of inadvertently transferring it to the eyes. Splinting is particularly useful at the thumb base.

Spine (facet joint) OA

Affects the cervical or lumbar facet joints, producing axial neck or low back pain, sometimes with a referred pain pattern. Actively look for red-flag neurological features (radiculopathy, myelopathy) that point to a different, more urgent process than uncomplicated facet OA.

Risk Factors

Older age.
Obesity/higher body mass index — the single most important modifiable risk factor for knee OA, related to both mechanical joint loading and abnormal lipid/metabolic effects on cartilage.
Female sex.
Joint malalignment — genu valgum or genu varum for knee OA.
Prior joint trauma or surgery, including resulting malalignment.
Prior joint infection (septic arthritis) or another inflammatory arthropathy affecting the same joint.
Repetitive occupational or athletic joint loading.
Quadriceps muscle weakness (knee OA).
Genetic/hereditary predisposition, particularly for hand OA.
An underlying congenital joint abnormality (e.g., hip dysplasia).
A metabolic or hematologic disease predisposing to secondary OA — gout, calcium pyrophosphate deposition disease (CPPD/pseudogout), hemochromatosis, and hematologic/genetic disorders such as hemophilia or leukemia-related joint disease.

Red Flags & Refer

OA is a diagnosis of exclusion in any patient whose presentation does not fit the classic pattern below — do not assume OA in an atypical presentation.

Signs of septic arthritis — a single hot, swollen, exquisitely tender joint with fever or systemic illness — needs emergency joint aspiration and management, not a routine OA workup.
Signs of inflammatory arthritis — symmetric small-joint synovitis, prolonged morning stiffness of an hour or more, or systemic symptoms (fatigue, weight loss, low-grade fever) — need rheumatology referral rather than OA management.
Significant acute trauma or suspected fracture.
Sudden joint locking, giving way, or instability, suggesting an internal derangement (meniscal tear, loose body) rather than uncomplicated OA — refer for orthopedic assessment.
Cervical or lumbar spine OA with new radicular pain, limb weakness, gait disturbance, or bowel/bladder change — these suggest myelopathy or significant nerve root compromise and need urgent spine/neurosurgical referral, not routine facet-joint management.
Unexplained joint swelling or mass, night pain, or systemic symptoms raising concern for malignancy — investigate urgently rather than assuming OA.
Unremitting pain and functional limitation despite optimized conservative therapy in a patient who is a reasonable surgical candidate — refer for orthopedic surgical assessment for possible joint replacement rather than continuing to escalate medication indefinitely.

Assessment & Diagnosis

Differentiating osteoarthritis from its common mimics

Feature	Osteoarthritis	Rheumatoid arthritis	Gout / CPPD (pseudogout)	Septic arthritis
Onset	Gradual, over months to years	Gradual to subacute, over weeks to months	Acute, over hours	Acute, over hours to 1-2 days
Joint pattern	Asymmetric; DIP/PIP/thumb base, knees, hips, spine facets	Symmetric; MCP/PIP/wrists, characteristically sparing the DIP joints	Usually monoarticular (classically the 1st MTP joint for gout); CPPD often affects the knee or wrist	Usually monoarticular, most often the knee
Morning stiffness	Under 30 minutes	An hour or more	Not a prominent feature	Not a prominent feature — pain is constant
Inflammatory signs	Absent to mild; an effusion is possible but the joint is not hot/erythematous	Present — warm, swollen, tender joints with systemic fatigue	Marked — hot, red, exquisitely tender joint	Marked — hot, red, exquisitely tender joint, often with fever/systemic illness
Key investigation	Clinical diagnosis; weight-bearing x-ray only if imaging is genuinely needed	Rheumatoid factor, anti-cyclic citrullinated peptide antibody, elevated ESR/CRP	Synovial fluid microscopy: negatively birefringent urate crystals (gout) or positively birefringent rhomboid crystals (CPPD)	Synovial fluid Gram stain and culture — the test that must not be skipped

History

Joint stiffness usually lasting under 30 minutes, with pain and/or dysfunction on specific movements.
Absence of signs or symptoms of another inflammatory arthritis (symmetric small-joint involvement, prolonged stiffness, systemic symptoms).
A prior joint insult — trauma, infection, or another inflammatory arthropathy — or a personal/family history of a genetic, biochemical, or metabolic disease that predisposes to secondary OA.

Physical examination

Pain, stiffness, and limitation of both active and passive joint movement.
Deformity, muscle atrophy, and ligament tenderness in one or more affected joints.
Ligament and capsular laxity with muscle atrophy, producing joint instability and, in later stages, deformity.
Joint effusion, and audible or palpable crepitus with active flexion/extension.

Imaging

When imaging is — and is not — needed

A patient over 45 years old with activity-related joint pain and morning stiffness under 30 minutes can be diagnosed with OA clinically — imaging is not required to make the diagnosis in this typical presentation.^[1] Reserve x-rays for diagnostic uncertainty, atypical features, or pre-procedure/pre-surgical planning.

Weight-bearing x-rays (with a flexed patellofemoral/"skyline" view for the knee) are the imaging modality of choice when imaging is indicated. Recognized radiographic features are joint space narrowing, osteophyte formation, subchondral cysts (geodes), and subchondral sclerosis.
There is often a real mismatch between radiographic severity and symptom severity — significant structural damage can occur with minimal symptoms, and severe pain can occur with only minor radiographic change. Do not use x-ray findings alone to decide whether or how aggressively to treat.
Chondrocalcinosis (calcium pyrophosphate deposition) on x-ray suggests an underlying metabolic disorder predisposing to secondary OA and CPPD.
MRI has a limited role — it is less cost-effective than plain radiography for diagnosing OA itself, but is useful for evaluating a suspected soft-tissue injury (e.g., meniscal tear) or an atypical presentation. CT can be used if MRI is contraindicated.

Laboratory testing

Routine bloodwork is not needed to diagnose typical OA.
Order inflammatory markers (CBC, ESR, CRP, rheumatoid factor, anti-cyclic citrullinated peptide antibody) only when another inflammatory arthritis is genuinely suspected on history/exam — not as a routine screen in a patient with a typical OA presentation.
Synovial fluid analysis is valuable primarily to exclude infection when an effusion is present, to exclude gout, and — less commonly — to identify CPPD crystals as a contributing factor; it is not a routine test in straightforward OA.

Treatment Targets

Reduce or eliminate joint pain.
Improve or restore joint function, mobility, and independence in daily activities.
Improve the strength of the muscles supporting the joint, to protect cartilage, ligaments, and the joint capsule.
Slow or limit further structural damage to cartilage and supporting joint structures where possible.
Minimize cumulative drug-related harm — avoid unnecessary long-term NSAID, opioid, or oral corticosteroid exposure.
Preserve or restore the patient's ability to work, exercise, and take part in valued activities.

Choose Initial Treatment

Direct treatment rule

Foundation of therapy

1st line, every patient Structured exercise, weight management for a patient who is overweight or has obesity, and patient education are the foundation of OA management for every patient and every joint from the moment of diagnosis — start these alongside any pharmacologic therapy, not only after drug treatment has failed.^[2]

Topical vs oral as the first pharmacologic step

1st line, knee or hand OA Begin with a topical NSAID (e.g., diclofenac diethylamine gel) before an oral NSAID, particularly in patients aged 75 years or older or with elevated GI/renal/cardiovascular risk — topical NSAID delivers comparable relief for hand and knee pain to an oral NSAID with substantially lower systemic drug exposure.

Not effective for hip OA Topical therapy does not penetrate deeply enough to treat hip OA — move directly to an oral or injectable option for the hip.

Oral NSAID selection — stratify by GI and cardiovascular risk before choosing an agent

If topical therapy and/or acetaminophen are insufficient, initiate an oral NSAID at the lowest effective dose, selected according to the patient's individual risk profile rather than by habit.

Low GI/CV risk Use a standard nonselective NSAID (e.g., naproxen or ibuprofen at a low-to-moderate dose) for the shortest effective duration.

Elevated GI risk (age ≥65, prior GI bleed, concurrent ASA/anticoagulant/corticosteroid/SSRI use, or multiple concurrent NSAID use, including low-dose ASA) Co-prescribe a proton pump inhibitor with a nonselective NSAID, or use a COX-2-selective agent (celecoxib) together with a PPI for the highest-GI-risk patients.

High cardiovascular risk (ischemic heart disease, cerebrovascular disease, peripheral arterial disease, or severe heart failure) Avoid all NSAIDs, including COX-2 inhibitors — use topical therapy, acetaminophen, duloxetine, or an intra-articular option instead. Where an NSAID truly cannot be avoided in a patient with lower-grade cardiovascular risk factors, use low-dose naproxen or ibuprofen for the shortest possible duration and monitor blood pressure.

Dose ceilings that raise cardiovascular risk Do not exceed celecoxib 200 mg/day, diclofenac 100 mg/day, ibuprofen 1200 mg/day, or naproxen 750 mg/day in a patient with any cardiovascular risk factor — MI and stroke risk rises with higher daily NSAID dose.

Acetaminophen's role

Limited-benefit option, not a default first choice Acetaminophen provides at most a modest analgesic effect in OA, and current meta-analyses show only minimal pain relief versus placebo — it is a reasonable option for a patient who wishes to avoid NSAID risk entirely, or as an adjunct, but should not be assumed superior to, or a mandatory step before, a topical NSAID. Trial the maximum appropriate dose for 1-2 weeks to judge individual response before continuing it long-term.

Escalation beyond topical/oral therapy

Special situation — inadequate response to optimized topical/oral therapy, or a poor surgical candidate Consider an intra-articular corticosteroid injection for knee or hip OA, limited to no more than 3-4 injections per joint per year.

Special situation — centralized/widespread pain or coexisting depression Add duloxetine, starting at 30 mg daily.

Special situation — refractory pain and function loss despite optimized nonpharmacologic and pharmacologic therapy Refer for orthopedic surgical assessment for possible joint replacement — do not delay referral indefinitely while continuing to escalate medication in a patient who is otherwise a reasonable surgical candidate.

Non-Pharmacologic Treatment

Weight management — for knee OA in particular, excess weight is the single most important modifiable risk factor. Recommend a structured weight-management program for any patient who is overweight or has obesity; sustained weight loss over a longer period produces the best pain and function outcome, and this benefit occurs even without an accompanying increase in physical activity.
Exercise — recommend both resistance and land-based aerobic exercise. An optimal program has one clear aim (e.g., improving aerobic capacity), delivered as a structured course of roughly 12 sessions over 2-3 sessions per week; benefit can persist for 2-6 months after a course ends. Neuromuscular exercise (targeting sensorimotor control and functional stability) is also effective for hip and knee OA. Aquatic exercise is a reasonable alternative when land-based exercise is not tolerated, with benefit similar to cycling.
Yoga and tai chi may reduce pain and stiffness and improve function and quality of life.
Reassure patients that exercise is safe and beneficial in OA — a misinformed fear of "wearing out" the joint further is a common, correctable barrier to activity.
Patient education, including self-management programs and resources such as those offered by the Arthritis Society, improves pain management; cognitive behavioural therapy can be considered, particularly for widespread pain or a significant psychological component.
Orthotics and aids — shoe orthotics can help a patient with flat arches or midfoot/ankle malalignment; a knee brace produces a small-to-moderate pain reduction in some, but not all, patients with knee OA; splints improve hand pain and function, particularly at the thumb base; canes and walkers can be offered for hip and knee OA.
Multidisciplinary care — physiotherapy, occupational therapy, and pharmacist involvement alongside family/caregiver support improves outcomes beyond any single intervention alone.
TENS and extracorporeal shockwave therapy have limited, inconsistent evidence and are not a substitute for exercise and weight management.

Pharmacologic Treatment Options

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Diclofenac diethylamine gel Preferred	Topical NSAID — 1st-line pharmacotherapy for knee/hand OA	Apply twice daily (morning and evening); do not exceed 4 g/day across all treated areas	Local skin dryness/irritation, rare contact dermatitis or photosensitivity	Preferred over an oral NSAID as the first pharmacologic step, especially age ≥75. Do not apply to broken skin or near the eyes.
Capsaicin cream Alternative	Topical adjunct, knee OA only (not hand OA)	Apply 3-4 times daily to the affected joint	Transient burning/stinging at the application site, most pronounced with the first several applications	Wash hands immediately after applying; avoid eyes, mucous membranes, and broken skin. Not recommended for hand OA given the eye-contamination risk. Full effect may take 1-2 weeks of regular use.
Naproxen Preferred	Oral NSAID, preferred agent when cardiovascular risk is low-to-moderate	250-500 mg PO BID with food; do not exceed 1500 mg/day	Dyspepsia, GI ulcer/bleed, fluid retention, hypertension; MI/stroke risk lower than most other NSAIDs at low dose	Take with food. A reasonable default oral NSAID choice. Add a PPI if GI risk factors are present.
Celecoxib Special situation	COX-2-selective oral NSAID — elevated GI risk without high cardiovascular risk	100 mg PO BID or 200 mg PO once daily; do not exceed 200 mg/day for OA	Dyspepsia, edema, hypertension; lower GI bleed risk than nonselective NSAIDs, but not lower cardiovascular risk	Combine with a PPI for the highest-GI-risk patients. Avoid entirely in ischemic heart disease, cerebrovascular disease, or heart failure.
Diclofenac potassium Alternative	Oral NSAID alternative	25-50 mg PO BID-TID with food; do not exceed 100-150 mg/day	Dyspepsia, GI ulcer/bleed, hypertension, fluid retention	Carries a comparatively higher cardiovascular risk among nonselective NSAIDs, especially above 100 mg/day — avoid in ischemic heart disease, cerebrovascular disease, or peripheral arterial disease.
Acetaminophen Alternative	Simple analgesic — limited but genuine benefit	325-1000 mg PO Q4-6H; max 4 g/day (max 2-3 g/day in frail elderly, hepatic impairment, malnourishment, or regular alcohol use)	Hepatotoxicity with excess intake or in at-risk patients; minimal effect on the GI, renal, or cardiovascular systems at recommended dose	Current meta-analyses show only minimal pain relief versus placebo — do not treat as automatically superior to a topical NSAID. Counsel on checking combination products for hidden acetaminophen content.
Duloxetine Special situation	Centralized/widespread OA pain, or coexisting depression	Start 30 mg PO daily; increase to 60 mg daily after 1-2 weeks; max 120 mg/day	Nausea, dry mouth, somnolence, dizziness, increased fall risk in older adults	On the 2023 AGS Beers Criteria list for fall/fracture risk in older adults. Do not stop abruptly. Contraindicated in severe hepatic or renal impairment (ClCr under 30 mL/min).
Tramadol Special situation	Moderate-to-severe pain unresponsive to other therapy	Start low and titrate slowly per the specific product's labelling; use the lowest effective dose	Sedation, nausea, constipation, seizure risk, serotonin syndrome risk with serotonergic drugs, dependence potential	Reserve for a patient who has not responded to, or cannot use, NSAIDs/acetaminophen, following the 2017 Canadian opioid-prescribing guideline.<cite data-reference-id="c3d9c3cf-81fb-4cf2-863d-4c9bee5fe087"></cite> Start at a lower dose in older adults.
Triamcinolone acetonide (intra-articular) Special situation	Intra-articular injection for knee/hip OA with inadequate response to oral/topical therapy	Large joint: 5-40 mg per injection; small joint: 2.5-10 mg per injection, by a trained injector	Local post-injection flare, skin/fat atrophy, infection (rare); possible worsening of pain/joint deterioration with frequent use	Limit to a maximum of 3-4 injections per joint per year. Advise minimal joint activity for 3 days after injection. Benefit typically lasts 4-6 weeks.

Non-tramadol opioids (e.g., morphine, oxycodone) are deliberately not included above as a routine option — they have not shown long-term value in OA and are reserved as a genuine last resort per the treatment-failure sequence and the 2017 Canadian opioid-prescribing guideline.^[3] See Drug Tables for full dosing if used.

Special Populations

Pregnancy

OA itself is uncommon during the reproductive years, but a pregnant patient with pre-existing OA still needs a therapy plan. Acetaminophen at usual doses is the preferred analgesic in pregnancy. Avoid oral and topical NSAIDs, especially from 20 weeks' gestation onward and absolutely in the third trimester, given the risk of premature closure of the fetal ductus arteriosus and reduced amniotic fluid — this applies to topical diclofenac as well as oral agents, since even low systemic absorption carries this risk in late pregnancy. Duloxetine and tramadol are not first-choice options in pregnancy; use only if benefit clearly outweighs risk and no better alternative exists. Intra-articular corticosteroid injection can be considered case-by-case using the lowest effective dose.

Breastfeeding

Acetaminophen and topical NSAID use (avoiding the breast area) are compatible with breastfeeding. Oral NSAIDs at standard doses are generally considered compatible with breastfeeding for short courses; naproxen is preferred among the NSAIDs by some sources given its long track record. Duloxetine and tramadol both pass into breast milk in small amounts — use the lowest effective dose and monitor the infant, or select an alternative where reasonable.

Older adults

Start at a low dose and titrate slowly given the higher prevalence of polypharmacy and drug interactions in this age group. Prefer topical NSAID over oral NSAID as the first pharmacologic step. Avoid nonselective oral NSAIDs and COX-2 inhibitors where possible per the 2023 AGS Beers Criteria, particularly with chronic use or in a patient on an oral anticoagulant, corticosteroid, or with a GI bleed history — use the lowest effective dose for the shortest duration if an oral NSAID cannot be avoided.^[4] Duloxetine and other SNRIs are on the same Beers list for increased fall/fracture risk. Non-tramadol opioids carry a substantial fall and fracture risk and should not be used routinely in this population.

Renal impairment

Avoid NSAIDs — including a topical NSAID used over a large area or for a prolonged period — at an estimated creatinine clearance under 30 mL/min. Duloxetine is contraindicated in severe renal impairment (ClCr <30 mL/min). Tramadol requires dose reduction and a longer dosing interval in significant renal impairment.

Hepatic impairment

Acetaminophen is not contraindicated in liver disease but requires closer AST/ALT monitoring and a lower total daily dose (2-3 g/day) to guide treatment; a history of alcohol use disorder, malnourishment, or being significantly underweight further raises hepatotoxicity risk at any given dose. Duloxetine is contraindicated in severe hepatic impairment/chronic liver disease.

Cardiovascular disease

Avoid all NSAIDs, including COX-2-selective agents, in a patient with established ischemic heart disease, cerebrovascular disease, peripheral arterial disease, or severe heart failure — use topical therapy, acetaminophen, duloxetine, or an intra-articular option instead. In a patient presenting with unstable angina or NSTEMI, discontinue any nonselective NSAID or COX-2 inhibitor (aside from low-dose ASA) because of the added cardiovascular risk.

Pediatrics

OA is a disease of adulthood; joint pain and swelling in a child or adolescent should prompt evaluation for juvenile idiopathic arthritis or another pediatric rheumatologic condition rather than being managed as OA.

Monitoring & Follow-Up

Reassess pain and function at each visit, including whether nonpharmacologic measures (exercise, weight management) are genuinely being followed, not just the drug regimen. For any patient on chronic oral NSAID therapy, periodically check blood pressure, renal function, and ask directly about GI symptoms (dyspepsia, melena, unexplained fatigue suggesting occult blood loss); dyspepsia without alarm features does not require stopping the NSAID outright but should prompt a class switch or symptomatic treatment. Track total daily acetaminophen intake across all products at every visit, particularly in a patient also taking a combination analgesic that contains acetaminophen. Check AST/ALT periodically in patients with liver disease or another hepatotoxicity risk factor who are taking regular acetaminophen. Limit intra-articular corticosteroid injections to a maximum of 3-4 per joint per year and reassess response after each course before repeating. Reassess candidacy for orthopedic surgical referral over time rather than only at the point of treatment failure — earlier surgical referral in an appropriate candidate can meaningfully protect quality of life and help prevent secondary complications of prolonged immobility such as worsening obesity, hypertension, and cardiovascular disease.

Treatment Failure / Next Step

Confirm the nonpharmacologic foundation — exercise adherence and weight-management progress — has genuinely been optimized before escalating pharmacotherapy; drug therapy added on top of an unaddressed nonpharmacologic gap rarely succeeds.
Confirm correct topical NSAID technique and adherence before assuming it has failed and moving to an oral agent.
If an oral NSAID causes dyspepsia without alarm features, switch to a different NSAID class or add gastroprotection (a PPI, or switch to a COX-2-selective agent) rather than abandoning NSAID therapy outright.
If topical and oral therapy together provide inadequate relief, consider an intra-articular corticosteroid injection for knee or hip OA.
If pain has clearly centralized or become widespread, or depression coexists, add duloxetine.
If response remains inadequate despite all of the above, reassess the diagnosis itself — rule out an alternative or superimposed condition (inflammatory arthritis, CPPD, gout, mechanical internal derangement) rather than continuing to escalate OA therapy against an incorrect diagnosis.
If conservative therapy has been genuinely exhausted and structural disease on imaging and exam supports it, refer for orthopedic surgical assessment.

Common Errors to Avoid

Assuming acetaminophen must always be tried before a topical NSAID — current evidence shows only minimal benefit from acetaminophen, while topical NSAID has genuine first-line evidence for knee/hand OA.
Using topical capsaicin for hand OA — not recommended given the risk of inadvertent eye contamination from the fingers.
Prescribing an oral corticosteroid for chronic OA pain — not recommended given the risk of osteoporosis and osteonecrosis, with no established role outside short-term specialist-directed use for an acute flare.
Exceeding 3-4 intra-articular corticosteroid injections per joint per year — an excessive number raises the risk of a Charcot-type arthropathy (progressive bone resorption and deformity) and possible cartilage/joint deterioration.
Combining two oral NSAIDs simultaneously (aside from continuing low-dose cardioprotective ASA) — this adds toxicity risk without added benefit.
Continuing a nonselective NSAID or COX-2 inhibitor (aside from low-dose ASA) in a patient presenting with unstable angina or NSTEMI.
Recommending glucosamine and/or chondroitin as though they were evidence-supported first-line therapy — current guidelines recommend against them for knee and hip OA (chondroitin has a narrow conditional recommendation for hand OA only).
Reflexively prescribing a non-tramadol opioid for chronic OA pain — these have not shown long-term value in OA and carry a disproportionate fall, fracture, and misuse risk relative to benefit; reserve as a genuine last resort.
Missing an alternative or coexisting diagnosis — septic arthritis, inflammatory arthritis, gout/CPPD, or malignancy — in a patient whose presentation does not fit the typical OA pattern.
Not asking about every source of acetaminophen a patient is taking, including nonprescription combination products, before adding a prescription acetaminophen-containing product.
Telling a patient that exercise will worsen their OA — this misinformation is a common, correctable barrier to one of the most effective available interventions.

Clinical Decision Algorithm

Algorithm A — Initial assessment and first-line therapy

Joint pain with morning stiffness under 30 minutes, activity-related pain, and no red-flag features

Confirm a typical OA presentation; rule out septic arthritis, inflammatory arthritis, and other red flags

Knee or hand OA

Start structured exercise + weight management (if overweight) + education, and begin a topical NSAID

Reassess after a defined trial — proceed to Algorithm B if inadequate

Hip OA

Start structured exercise + weight management (if overweight) + education — topical therapy is not effective for hip OA, so move directly to oral therapy if needed (Algorithm B)

Algorithm B — Pharmacologic escalation and GI/CV risk stratification

Nonpharmacologic therapy optimized; topical NSAID (knee/hand) inadequate, or hip OA present

Assess individual GI and cardiovascular risk before selecting an oral NSAID

Low GI/CV risk

Standard-dose nonselective NSAID (e.g., naproxen) for the shortest effective duration

Elevated GI risk, low CV risk

Nonselective NSAID plus a PPI, or celecoxib ± a PPI if GI risk is highest

High CV risk (ischemic heart disease, stroke, peripheral arterial disease, severe heart failure)

Avoid all NSAIDs, including COX-2 inhibitors — use acetaminophen, duloxetine, or an intra-articular option instead

Reassess response

Inadequate response

Consider an intra-articular corticosteroid injection (knee/hip) and/or duloxetine for centralized pain

Still inadequate and a reasonable surgical candidate: refer for orthopedic joint-replacement assessment

Good response

Continue the current regimen; reassess periodically and step down if possible

Drug Tables

How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment and individual GI/cardiovascular risk stratification (see Choose Initial Treatment). Select any drug name to open its complete Pharmasist Drug Database page.

Topical agents

Drug	Dosage	Adverse effects	Drug interactions	Comments
Diclofenac diethylamine gel	Adults: Apply twice daily (morning and evening); do not exceed 4 g/day across all treated areas	Local skin dryness/irritation, rare contact dermatitis or photosensitivity; serious systemic GI/CV toxicity not established in trials given minimal absorption	Minimal — systemic absorption is low; isolated reports of increased INR/bleeding with concurrent anticoagulant use	Preferred first pharmacologic step for knee/hand OA, especially age ≥75 or elevated systemic NSAID risk. Available without a prescription. Do not use on broken skin or near the eyes. Contraindicated in the third trimester of pregnancy.
Diclofenac sodium topical solution (Pennsaid)	Adults, knee OA: Apply per product labelling; approved for up to 3 months of continuous or intermittent use	Local skin dryness, application-site reactions	Same class-level cautions as other topical NSAIDs	A distinct diclofenac sodium 1.5% topical solution approved specifically for knee OA — a different salt and formulation from the diclofenac diethylamine gel above. No Pharmasist Drug Database monograph is currently published for this product.
Capsaicin cream	Adults: Apply 3-4 times daily to the affected joint	Transient burning/stinging at the application site, most pronounced with the first several applications	None significant — minimal systemic absorption	Conditionally recommended for knee OA; not recommended for hand OA given the risk of transferring the product to the eyes. Wash hands immediately after application. Marketed as a nonprescription product.

Oral NSAIDs — acetic acid derivatives

Drug	Dosage	Adverse effects	Drug interactions	Comments
Diclofenac potassium	Adults: 25-50 mg PO BID-TID with food; do not exceed 100-150 mg/day	Dyspepsia, GI ulcer/bleed, hypertension, edema, elevated transaminases, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Carries a comparatively higher cardiovascular risk among nonselective NSAIDs, especially above 100 mg/day — avoid in ischemic heart disease, cerebrovascular disease, or peripheral arterial disease. Avoid at ClCr under 30 mL/min.
Indomethacin	Adults: 50-200 mg/day PO in 2-3 divided doses	Dyspepsia, GI ulcer/bleed, headache (common), dizziness, confusion (especially in older adults)	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Not commonly used for OA given a higher CNS side-effect burden relative to other NSAIDs; avoid at ClCr under 30 mL/min.
Sulindac	Adults: 150-200 mg PO BID	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Avoid with a history of peptic ulcer disease, cardiovascular risk factors, renal failure, heart failure, or asthma; avoid at ClCr under 30 mL/min.

Oral NSAIDs — naphthylalkanone derivative

Drug	Dosage	Adverse effects	Drug interactions	Comments
Nabumetone	Adults: 1000 mg PO once daily, may increase to 2000 mg/day in 1-2 divided doses	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	A prodrug converted to its active metabolite; the same class-level GI/CV/renal cautions apply.

Oral NSAIDs — oxicams

Drug	Dosage	Adverse effects	Drug interactions	Comments
Piroxicam	Adults: 10-20 mg PO once daily	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	A long half-life allows once-daily dosing; the same class-level cautions apply.

Oral NSAIDs — propionic acid derivatives

Drug	Dosage	Adverse effects	Drug interactions	Comments
Ibuprofen	Adults: 200-600 mg PO Q6-8H; max 2400 mg/day	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs. May reduce the antiplatelet effect of ASA — give ibuprofen at least 30 minutes after, or 8 hours before, low-dose ASA.	Doses of 2400 mg/day or more carry increased stroke/CV event risk and should not be used in a patient with cardiovascular disease or cardiovascular risk factors.
Naproxen	Adults: 250-500 mg PO BID; max 1500 mg/day	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Among the nonselective NSAIDs, naproxen may carry the lowest relative cardiovascular risk, making it a reasonable default oral NSAID choice when one is needed.
Naproxen sodium	Adults: 220-550 mg PO BID	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Same active drug as naproxen above in a different salt/strength labelling; nonprescription strength is 220 mg per tablet.
Ketoprofen	Adults: 50-75 mg PO TID-QID	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Same class-level cautions as other propionic acid derivatives.
Flurbiprofen	Adults: 50-100 mg PO BID-TID	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Same class-level cautions as other propionic acid derivatives.
Tiaprofenic acid	Adults: 200-300 mg PO BID	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness; rare severe cystitis reported with prolonged use	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Advise a patient to report new urinary symptoms promptly given the rare cystitis association.

Oral NSAIDs — salicylic acid derivatives

Drug	Dosage	Adverse effects	Drug interactions	Comments
ASA (anti-inflammatory dose)	Adults: 325-650 mg PO Q4H	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness, tinnitus at high dose	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	Not commonly used for OA at anti-inflammatory doses given GI risk relative to other NSAIDs. Do not combine with another NSAID (aside from continuing a separately prescribed low-dose cardioprotective ASA).
Diflunisal	Adults: 250-500 mg PO BID	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	A salicylate-derivative NSAID with the same class-level GI/CV/renal cautions. No Pharmasist Drug Database monograph is currently published for this less commonly prescribed agent.

COX-2-selective / preferential oral NSAIDs

Drug	Dosage	Adverse effects	Drug interactions	Comments
Celecoxib	Adults: 100 mg PO BID or 200 mg PO once daily	Dyspepsia, edema, hypertension; lower relative GI bleed risk than nonselective NSAIDs	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium.	Not lower cardiovascular risk than nonselective NSAIDs — avoid in ischemic heart disease, cerebrovascular disease, heart failure, or serious cardiac disease. Combine with a PPI for the highest-GI-risk patients. Evidence of cross-reactivity with sulfonamide allergy is lacking, though caution is still reasonable.
Meloxicam	Adults: 7.5-15 mg PO once daily	Dyspepsia, GI ulcer/bleed, hypertension, edema, dizziness	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	COX-2 preferential, not fully selective, at usual OA doses — the same class-level GI/CV/renal cautions as other nonselective NSAIDs apply, particularly at the higher end of the dose range.

Simple analgesics

Drug	Dosage	Adverse effects	Drug interactions	Comments
Acetaminophen	Adults, immediate release: 325-1000 mg PO Q4-6H Adults, sustained release: 650 mg PO Q8H Maximum, general: 4 g/day Maximum, frail elderly/hepatic impairment/malnourished/underweight under 50 kg/regular alcohol use: 2-3 g/day	Hepatotoxicity with excess intake or in at-risk patients	Alcohol increases hepatotoxicity risk, especially during withdrawal (induced CYP2E1 activity persists 3-8 days); may increase INR with warfarin — check INR if ≥2 g/day is used for 3 or more consecutive days.	Trial the maximum appropriate dose for 1-2 weeks to judge individual benefit — current meta-analyses show only minimal pain relief in OA versus placebo. Liver disease does not preclude use but requires closer AST/ALT monitoring. Counsel patients to check all products, prescription and nonprescription, for hidden acetaminophen content.

Centralized-pain agent

Consider when OA pain has centralized/widespread features or depression coexists.^[1]

Drug	Dosage	Adverse effects	Drug interactions	Comments
Duloxetine	Adults, starting dose: 30 mg PO daily Adults, target dose: 60 mg PO daily after 1-2 weeks Maximum: 120 mg/day	Nausea, dry mouth, constipation, somnolence, dizziness, insomnia, decreased appetite, increased fall risk	Avoid with strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin, ketoconazole) or MAOIs; caution with other serotonergic drugs (dextromethorphan, trazodone, triptans).	Do not stop abruptly. Contraindicated in severe hepatic or renal impairment (ClCr under 30 mL/min). On the AGS Beers list for fall/fracture risk in older adults.

Opioids

Reserve for a patient who has not responded to, or cannot use, NSAIDs/acetaminophen, following the 2017 Canadian opioid-prescribing guideline for chronic noncancer pain.^[3] Non-tramadol opioids have not shown long-term value in OA — reserve strictly as a last resort.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Tramadol	Immediate release: Start low; titrate per product labelling Controlled release: Start 100-150 mg PO daily depending on product; titrate weekly to a max of 300-400 mg/day depending on product	Sedation, ataxia, constipation, nausea, orthostatic hypotension, seizure risk	Do not use within 14 days of an MAOI; caution with drugs lowering seizure threshold (SSRIs, TCAs, bupropion) and serotonin-syndrome risk with SSRIs; CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) and CYP3A4 inhibitors (erythromycin, itraconazole, ketoconazole) can alter clearance.	Start at a lower dose in older adults. Immediate- and controlled-release products are dosed differently — follow the specific product's labelling.
Tramadol/acetaminophen (Tramacet)	Adults: 1-2 tablets PO Q4-6H; max 8 tablets/day	Same as tramadol, plus acetaminophen hepatotoxicity risk at excess dose	Same as tramadol; monitor total acetaminophen intake from all sources	A convenient fixed-dose combination (tramadol 37.5 mg / acetaminophen 325 mg per tablet); still subject to the total daily acetaminophen ceiling of 4 g/day from all sources.
Morphine (immediate release)	Adults, short-term adjunctive use only: 2.5-15 mg PO Q4H	Sedation, nausea, vomiting, constipation, increased fall risk	Additive sedation with other CNS depressants	Non-tramadol opioids preclude routine use in OA given a limited benefit-to-risk ratio — reserve as a last resort in a patient who has exhausted other options or has NSAID contraindications.
Oxycodone (immediate release)	Adults, short-term adjunctive use only: 5-10 mg PO Q4H	Sedation, nausea, vomiting, constipation, increased fall risk	Additive sedation with other CNS depressants	Same last-resort positioning as morphine above.

Natural health products — glucosamine and chondroitin. Endogenous glucosamine and chondroitin help maintain cartilage integrity, and exogenous supplementation was historically popular, but current guideline evidence review does not support this. Glucosamine is strongly recommended against for knee, hip, and hand OA. Chondroitin is strongly recommended against for knee and hip OA, but carries a narrow conditional recommendation for hand OA based on a single well-conducted, low-bias trial.^[1]^[5] Commonly studied doses, where a patient chooses to try one despite this guidance, are glucosamine sulfate around 1500 mg/day and chondroitin sulfate around 800-1200 mg/day; both have a good overall safety profile. No Pharmasist Drug Database monograph is linked here, since these products are not a recommended therapy and dosing/quality varies widely by product.

GI-protective adjuncts

For a patient on a nonselective NSAID or COX-2 inhibitor who has elevated GI risk factors.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Misoprostol	Adults: 200 mcg PO QID with the oral NSAID	Diarrhea, abdominal cramping — often dose-limiting	None significant beyond the co-administered NSAID's own interactions	Effective for preventing NSAID-induced GI complications but frequently not well tolerated; a PPI is generally better tolerated for the same purpose.
Omeprazole (PPI)	Adults: 20 mg PO once daily, taken with the NSAID	Headache, GI upset; long-term use associated with other class-level risks	May reduce clopidogrel activation	Preferred gastroprotective option for a patient at moderate-to-high GI risk on a nonselective NSAID, or combined with a COX-2 inhibitor for the highest-risk patients.
Diclofenac/misoprostol (fixed combination)	Adults: Per product labelling	Combines diclofenac's NSAID adverse effects with misoprostol's diarrhea/cramping	Increased bleeding with anticoagulants/antiplatelets; may reduce antihypertensive effect; may decrease renal clearance of lithium (monitor levels); increased GI bleed risk with SSRIs.	A fixed-dose combination product pairing an NSAID with built-in GI protection — the same cardiovascular and renal cautions as diclofenac apply.

Intra-articular corticosteroids

Guidelines support intra-articular corticosteroid injection for knee and hip OA when nonpharmacologic and oral/topical therapy provide inadequate relief; limit to a maximum of 3-4 injections per joint per year, since more frequent injection raises the risk of a Charcot-type arthropathy.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Betamethasone acetate/betamethasone sodium phosphate	Large joint (hip/knee/shoulder/ankle): 1 mL Medium joint (elbow/wrist): 0.5-1 mL Small joint (MCP/IP/sternoclavicular/acromioclavicular): 0.25-0.5 mL	No clinically significant systemic effect at usual dosing; long-term/repeated use may worsen pain and function or cause joint space narrowing/deterioration	None significant at intra-articular dosing	Inexpensive and effective for individual large-joint OA. Minimize joint activity for 3 days after injection. Benefit typically lasts 4-6 weeks.
Methylprednisolone acetate (± lidocaine)	Large joint: 20-80 mg Medium joint: 10-40 mg Small joint: 4-10 mg	No clinically significant systemic effect at usual dosing; long-term/repeated use may worsen pain and function or cause joint space narrowing/deterioration	Strong CYP3A4 inhibitors have been reported to interact	The Pharmasist Drug Database monograph linked here is the lidocaine-containing formulation (Depo-Medrol with Lidocaine) — a lidocaine-free methylprednisolone acetate product is also available and is often chosen when the injecting clinician plans to add a separate local anesthetic. Minimize joint activity for 3 days after injection.
Triamcinolone acetonide	Large joint: 5-40 mg Small joint: 2.5-10 mg	No clinically significant systemic effect at usual dosing; long-term/repeated use may worsen pain and function or cause joint space narrowing/deterioration	Strong CYP3A4 inhibitors have been reported to interact	Minimize joint activity for 3 days after injection. Benefit typically lasts 4-6 weeks.

Intra-articular hyaluronic acid / synovial fluid replacement

Guideline-discordant for knee OA: OARSI conditionally recommends FOR intra-articular hyaluronic acid,^[2] while the ACR/Arthritis Foundation conditionally recommends AGAINST it for knee OA and strongly AGAINST it for hip OA.^[1] Discuss this uncertainty explicitly with the patient before using it, rather than presenting it as settled.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Sodium hyaluronate / hyaluronic acid products (e.g., Synvisc, Monovisc, Durolane, Orthovisc)	Knee joint: A single injection, or weekly for 3-5 weeks depending on the specific product	Mild transient local reactions (pain, swelling, warmth, bruising); rare pseudosepsis reported with some products	None significant	A heterogeneous product class — no single Pharmasist Drug Database monograph exists; confirm the specific product's own labelling before administering. A combination hyaluronic acid/triamcinolone hexacetonide product also exists for a single knee injection.

References

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee — Arthritis Care & Research, American College of Rheumatology/Arthritis Foundation (Kolasinski SL, Neogi T, Hochberg MC, et al.). Arthritis Care Res 2020;72(2):149-162
OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis — Osteoarthritis and Cartilage, Osteoarthritis Research Society International (Bannuru RR, Osani MC, Vaysbrot EE, et al.). Osteoarthritis Cartilage 2019;27(11):1578-1589
Guideline for opioid therapy and chronic noncancer pain — CMAJ (Busse JW, Craigie S, Juurlink DN, et al., National Pain Centre, McMaster University). CMAJ 2017;189(18):E659-E666
American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults — Journal of the American Geriatrics Society (2023 American Geriatrics Society Beers Criteria® Update Expert Panel). J Am Geriatr Soc 2023;71(7):2052-2081
2018 update of the EULAR recommendations for the management of hand osteoarthritis — Annals of the Rheumatic Diseases, European Alliance of Associations for Rheumatology (Kloppenburg M, Kroon FP, Blanco FJ, et al.). Ann Rheum Dis 2019;78(1):16-24

Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.