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For free print copies of this summary, call 800-358-9295. Ask the Publications Clearinghouse for AHRQ Publication 11(12)-EHC076-3

Analgesics for Osteoarthritis

Clinician Summary – Feb. 15, 2012

Analgesics for Osteoarthritis


Table of Contents

Focus of Research for Clinicians

As an update to a 2006 report, a systematic review of 273 clinical studies published between January 2005 and January 2011 examined the comparative effectiveness, benefits, and adverse effects of analgesics and the supplements glucosamine and chondroitin for osteoarthritis. The review did not include studies on opioid medications or nonpharmacological interventions for osteoarthritis. The full report, listing all studies, is available at This summary, based on the full report of research evidence, is provided to inform discussions with patients of options and to assist in decisionmaking along with a patient’s values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.


Osteoarthritis is a chronic condition involving degradation of cartilage within the joints. It is the most common form of arthritis and is more common in older people. It is associated with pain, substantial disability, and reduced quality of life.

Common oral medications for osteoarthritis studied in this review were nonopioid medications, including selective and nonselective nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, salsalate, acetaminophen, over-the-counter dietary supplements (glucosamine and chondroitin), and topical agents (NSAIDs and rubefacients, including capsaicin). The over-the-counter supplements glucosamine and chondroitin have grown in popularity; however, these are not regulated by the United States Food and Drug Administration (FDA).

NSAIDs block cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2. An important role of COX-1 is to mediate the mucosal protection of the gastrointestinal (GI) mucosa, and COX-2 mediates effects on pain and inflammation.

By blocking COX-2 enzymes, NSAIDs decrease pain and inflammation. Nonselective NSAIDs block both COX-1 and COX-2. NSAIDs that block COX-1 can cause GI adverse effects, including bleeding. Selective or partially selective (in vitro) NSAIDs block mostly COX-2 and thus should be safer with regard to GI adverse effects. However, it is unclear if partially selective NSAIDs are truly different from nonselective NSAIDs because COX-2 selectivity may be lost at higher doses. The effects of in vitro COX-2 selectivity on clinical outcomes are uncertain.


When analgesics are compared to each other, none appears to offer greater benefits relative to adverse effects at this time. Trade-offs between benefits and adverse effects appear to differ across analgesics, increasing the need to consider individual patient priorities when choosing among these medications. No significant analgesic differences were found in the benefits offered by NSAIDs; however, differences in GI adverse effects must be balanced with associated cardiovascular (CV) risks. Evidence suggests that age, comorbid conditions, and concomitant medication are key considerations affecting decisionmaking.

The evidence concerning the use of glucosamine and chondroitin appears unresolved and may not directly apply to unregulated products available in the United States. There is evidence that the topical NSAID diclofenac works as effectively as the oral agent.

Clinical Bottom Line

Comparative Effectiveness of Oral Agents

NSAIDs versus NSAIDs

NSAIDs versus other agents

  • Acetaminophen was modestly inferior to NSAIDs in reducing osteoarthritic pain but was associated with less risk of GI adverse effects than were NSAIDs. evidence high
  • No clear difference was found between glucosamine* and oral NSAIDs for pain or function. Evidence from a systematic review of higher quality trials suggests that glucosamine had some small benefits for pain over placebo. evidence high
  • No clear difference was found between chondroitin and oral NSAIDs for pain or function. evidence low

*Note: Most trials showing therapeutic benefits from glucosamine were conducted with pharmaceutical-grade glucosamine not available in the United States. Therefore, the findings of these trials may not be applicable to currently available over-the-counter preparations.

Aspirin and salsalate

Comparative Adverse Effects of Oral Agents

GI Effects

CV Effects

Comparing Dosage and Duration of Treatment
Factors Affecting Outcomes

Demographic Subgroups

Pre-existing Disease

Concomitant Medication Use

Adding an H-2 Antagonist, Misoprostol, or a PPI on GI Adverse Effects Associated With NSAIDs
Topical Analgesics

COX = cyclooxygenase; CV = cardiovascular; GI = gastrointestinal; H-2 antagonist = histamine-2 receptor antagonist; NSAID = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor.

Strength of Evidence Scale

High: evidence high
There are consistent results from good-quality studies. Further research is very unlikely to change the conclusions.

Moderate: evidence medium
Findings are supported, but further research could change the conclusions.

Low: evidence low
There are very few studies, or existing studies are flawed.

Insufficient: evidence insufficient
Research is either unavailable or does not permit estimation of a treatment effect.

Gaps in Knowledge

What To Discuss With Your Patients

  • The importance of managing osteoarthritis-related pain and inflammation for improving quality of life and function.
  • The potential benefits and adverse effects associated with different types of analgesics based on the characteristics of the individual patient.
  • Individual patient values and preferences when considering the trade-offs between benefits and adverse effects of each treatment option.
  • Information on symptoms that indicate GI and/or CV adverse effects, and directions for when these symptoms should be reported.

Resource for Patients

Managing Osteoarthritis Pain With Medicines, A Review of the Research for Adults is a free companion to this clinician research summary. It can help patients talk with their health care professionals about the options for treating their osteoarthritis with analgesics. It provides:

  • Information about the symptoms of osteoarthritis.
  • Descriptions of the different analgesics.
  • Simplified summaries of the research on benefits and adverse effects for each analgesic.
  • Questions for patients to ask their doctor.

Ordering Information

To order free print copies, call the AHRQ Publications Clearinghouse at 800-358-9295.


The information in this guide is based on Comparative Effectiveness and Safety of Analgesics for Osteoarthritis: An Update of the 2006 Comparative Effectiveness Review, Comparative Effectiveness Review No. 38, prepared by the Oregon Evidence-based Practice Center under Contract No. HHSA-290-2007-10057-I for the Agency for Healthcare Research and Quality, October 2011. 

This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX. It was written by Amelia Williamson Smith, M.S., Thomas Workman, Ph.D., Ursula Braun, M.D., and Michael Fordis, M.D.