Doctor's Review: Medicine on the Move

October 27, 2021


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Cross currents in osteoarthritis

Osteoarthritis: improving patient self-management

Osteoarthritis (OA) affects over 10% of Canadians aged 15 and older, rising in incidence with age. It presents a management challenge for physicians and is a major cause of pain, disability and reduced quality of life for patients. According to Statistics Canada, 66% of Canadians with OA report using over-the-counter (OTC) remedies for their condition and 39% manage with prescription medications.1 What products are they taking — and are they using them appropriately?

A 2013 study of nearly 1000 people in the US from the National Institutes of Health Osteoarthritis Initiative (OAI) provides some insight into medication use by patients with knee OA. The most popular therapy was glucosamine, taken by 40% of participants. OTC nonsteroidal anti-inflammatory drugs (NSAIDs) were the most common analgesics, used by 27%, followed by 14% taking acetaminophen and 8% receiving prescription NSAIDs (Figure 1).2

The glucosamine challenge

The widespread use of glucosamine in the OAI study suggests that many patients will seek out glucosamine on their own and some will find it helpful. Clinical trials of glucosamine, mainly in knee OA, have had conflicting results, but the evidence-based Natural Medicines Comprehensive Database (NMCD; has rated glucosamine as “likely effective” for OA pain.3 In terms of safety, NMCD considers glucosamine “likely safe,” while several systematic reviews have consistently found it is very safe, with adverse events comparable to placebo.3–6

Glucosamine is available in three forms: glucosamine sulfate, glucosamine hydrochloride and N-acetylglucosamine, which can all be obtained in capsule, tablet, liquid and powder formulations. Glucosamine is often sold in combination with chondroitin, another joint matrix building block, but this may be unnecessary. The NMCD has found no reliable evidence that the combination is better than glucosamine alone, and less evidence for chondroitin alone than for glucosamine; it classifies chondroitin as “possibly effective” and “likely safe.”

The typical glucosamine dosage in trials is 1500 mg taken orally once daily or in three divided doses.7 However, with almost 66% of Canadian seniors taking 5 or more medications,8 patients considering glucosamine may already have a heavy pill burden. Another option is powder formulations, which can be mixed with food or beverages for greater ease of dosing.

Those choosing pills should look for once-daily products containing 1500 mg per capsule/tablet. If tolerability of 1500 mg all at once is a problem, they can try 500 mg 3 times a day.

Patients should also be aware that glucosamine products on the market can vary wildly in chemical potency. A University of Alberta study found that, among 13 samples of 500-mg glucosamine sulfate capsules commercially available in Canada, the actual percentage of free glucosamine base, compared to the stated amount, ranged from 108% to 41% (Figure 2). The authors noted that glucosamine is unstable and therefore must be complexed with salts, which may dilute the active ingredient if calculated incorrectly.9 In contrast, N-acetylglucosamine is extremely stable, even at 37°C for up to 12 days.10

Most glucosamine supplements are derived from crustacean shells, so people with known shellfish allergies are advised to avoid these products. However, shellfish-free vegetarian-sourced glucosamine supplements are available as an alternative for those with allergies or dietary restrictions.11

Rethinking acetaminophen

Acetaminophen is still guideline-recommended as a first-line pharmacologic treatment for OA, but with reservations, due to growing evidence of lower efficacy and more adverse effects than previously thought.12,6 A recent, extensive network meta-analysis concluded that acetaminophen is clinically ineffective for OA pain at any dose.13 A systematic review found that, even at standard analgesic doses (≤4 g/day), acetaminophen showed a dose-response relationship with AEs typically associated with NSAIDs: cardiovascular, renal and gastrointestinal (GI) adverse events, as well as increased mortality.14 Patients taking acetaminophen must not exceed 4 g/day and should be cautioned not to take combination products that may contain acetaminophen, such as OTC cold remedies.15,12

Glucosamine alternative to NSAID

Physicians are well aware of the risk of adverse events with NSAIDs, but what about patients? Reassuringly, the OAI medication use study suggests OA patients are using NSAIDs largely as recommended.2

One area of concern is NSAID use by patients over the age of 75. In the OAI, prescription NSAIDs were uncommon in this age group, used by less than 3%, compared to 10% of those under 65, and 6% of 65–74-year-olds. This prescribing pattern is in line with recommendations discouraging NSAIDs in patients at risk for adverse events due to comorbidities, including advanced age. However, older people continued to take OTC NSAIDs at virtually the same rates as their younger counterparts, putting themselves at risk for serious side effects.2,12

Older seniors should be encouraged to consult with their physicians on less-toxic alternatives to oral NSAIDs. One option for hand and knee OA is topical NSAIDs, which offer pain relief comparable to oral NSAIDs, with a far lower risk of GI and other systemic adverse events.16 The 2012 American College of Rheumatology (ACR) guidelines recommend topical NSAIDs instead of oral forms for hand and knee OA in patients 75 and older.15

Glucosamine may also be an appealing alternative to NSAIDs. A recent head-to-head study of glucosamine + chondroitin (GC) versus celecoxib in 606 patients with knee OA and moderate-to-severe pain found that GC was noninferior to celecoxib, offering comparable efficacy in improving pain, function, stiffness and joint swelling after 6 months, with good safety and tolerability.17Basic management of OA involves a combination of nonpharmacologic and pharmacologic approaches, with education, weight loss (if overweight or obese) and exercise forming the core set of interventions recommended for all patients.12,6,18,19

Exercise and weight loss benefits

Patients and physicians alike tend to underestimate the benefits of exercise in managing OA. A 2015 Cochrane review concluded that land-based exercise improves pain, physical function and quality of life in knee OA, with benefits lasting at least 2–6 months after a formal program, and a treatment effect comparable to that of NSAIDs (but without the adverse effects).20

Obesity is a major modifiable risk factor for the development and progression of OA. Even modest weight loss can be helpful, since every kilogram of weight lost translates to a 4-kg decrease in the load on an arthritic knee with each step taken.21 Weight loss of >5% over 20 weeks reduces disability and, to a lesser extent, pain in knee OA.22

OA self-management education programs are strongly recommended, based on high-quality evidence for benefits in pain and physical function.19 Successful OA management requires individualized treatment and active involvement of informed, empowered patients.

This article was accurate when it was published. Please confirm rates and details directly with the companies in question.


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