Osteoarthritis

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.

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.

• 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.

Differentiating osteoarthritis from its common mimics

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

• 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.

• 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.

• 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.

Pregnancy

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.

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.

1. 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.
2. Confirm correct topical NSAID technique and adherence before assuming it has failed and moving to an oral agent.
3. 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.
4. If topical and oral therapy together provide inadequate relief, consider an intra-articular corticosteroid injection for knee or hip OA.
5. If pain has clearly centralized or become widespread, or depression coexists, add duloxetine.
6. 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.
7. If conservative therapy has been genuinely exhausted and structural disease on imaging and exam supports it, refer for orthopedic surgical assessment.

• 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.

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

Oral NSAIDs — acetic acid derivatives

Oral NSAIDs — naphthylalkanone derivative

Oral NSAIDs — oxicams

Oral NSAIDs — propionic acid derivatives

Oral NSAIDs — salicylic acid derivatives

COX-2-selective / preferential oral NSAIDs

Simple analgesics

Centralized-pain agent

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

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.

GI-protective adjuncts

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

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.

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.