The authors of A Rallying Call for Nonsteroidal Anti-Inflammatory Drugs in Musculoskeletal Pain: Improving Value of Care While Combating the Opioid Epidemic point out that despite being only 2% of all medical providers, orthopaedic surgeons represent 11% of the high-volume opioid prescribers and are in the top 10% of opioid prescription writers yearly.

Among us there is a high rate of opioid prescription generation for non-postoperative pain; for example, among patients presenting to a single center for arthritic hip or knee pain, 22.8% were prescribed opioids on their initial visit. 19% of orthopaedic trainees wrote prescriptions for amounts of opioids exceeding the recommended limits. These authors opine that the pain-relieving capabilities of nonsteroidal anti-inflamatory drugs (NSAIDs) represents a untapped opportunity for us to impact the opioid crisis.

They make several important points:

First, for nonoperative management of osteoarthritis, NSAIDs represent a key value-based treatment option that fulfills the requirements for efficacy and lower costs. The efficacy of NSAIDs is supported by clinical practice guidelines from the American Academy of Orthopaedic Surgeons (AAOS) and the American College of Rheumatology (ACR) based on high quality published studies. As an example, the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial was a randomized study that compared the effect of opioid versus nonopioid medications (including NSAIDs) on pain-related function, pain intensity, and adverse events in patients with chronic back pain or hip and knee OA. While pain-related function was comparable over 12 months, both pain intensity and adverse events were significantly lower in the non-opioid treatment arm.

Second, in contrast to the clear positions of the AAOS and the ACR, other medical specialties (e.g., family medicine, internal medicine, geriatrics, and physical therapy) do not have recommendations pertaining to the use of NSAIDs. The lack of clear indications and contraindications among different specialties often results in variable interpretations at the provider level, leading to confusion among patients as to whether NSAIDs can be used safely and effectively. As a result, in clinical practice, treatments such as injections and opioids are used more frequently for OA treatment than NSAIDs even though they have not been supported by the current AAOS CPGs.

Third, several safety concerns exist about NSAIDs, including the potential for gastrointestinal (GI) and cardiovascular (CV) adverse events, renal toxicity, and impaired bone-healing.

(a) While the potential GI side effects of NSAIDs have been well-established, most studies have focused on nonselective cyclooxygenase (COX) inhibitors and have failed to exclude patients who concurrently have been taking other medications that are known to cause GI side effects (e.g., aspirin). The gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN) trial was a double-blinded RCT that compared the GI safety of celecoxib (a selective COX-2 inhibitor) with naproxen (a nonselective COX inhibitor) in patients with OA, cardiovascular disease (CVD), and recent upper GI bleeding. Recurrent GI bleeding was found in 5.6% of individuals who were taking celecoxib compared with 12.3% of those taking naproxen. This study also found that NSAIDs should not be considered contraindicated simply based on advanced age; rather, the decision should be guided by patient risk factors. In addition, adding proton pump inhibitors (PPIs) to NSAIDs reduces adverse GI events when compared with the use of NSAIDs alone. The combination of selective COX-2 inhibitors and PPIs may further reduce the risk of adverse GI events.

(b) The potential adverse CV effects of NSAIDs are another common concern. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial was a large RCT that compared the CV safety of celecoxib, naproxen, and ibuprofen when utilized for arthritis treatment. Compared with nonselective COX inhibitors, including naproxen and ibuprofen, celecoxib had a lower risk of adverse CV events. Collectively, these studies demonstrate the differential effects of NSAIDs on CV health and emphasize the need to identify high-risk patients.

(c) The potential nephrotoxicity of NSAIDs is another concern. The International Society of Nephrology recommends the avoidance of NSAIDs in those with chronic kidney disease especially those with a glomerular filtration rate (GFR) of <30 mL/min/1.73 m². However, more rigorous studies and clearer guidelines are necessary to help clinicians navigate the use of NSAIDs in the subset of patients with CKD.

(d) Orthopaedic surgeons are frequently concerned about the potential negative impact of NSAIDs on bone-healing. However, a recent study by the Orthopaedic Trauma Association (OTA) Musculoskeletal Pain Task Force determined that there is no conclusive evidence demonstrating the detrimental effect of NSAIDs on bone-healing and recommended the routine use of NSAIDs in fracture care. Currently, there is no definitive clinical evidence that NSAIDs impair fracture-healing.

In summary, NSAIDs remain an underutilized class of medications in orthopaedic surgery. Available evidence suggests that opioids are not superior to NSAIDs in improving pain-related function, including in patients with back pain and major-joint arthritis. While concerns regarding the use of NSAIDs are valid, providers should maintain a level of realistic caution so as not to deprive patients of their potential benefits. All NSAIDs are not equal in terms of their safety profiles. To date, there exists a major gap in our knowledge regarding clear and well-accepted interdisciplinary contraindications for NSAID use. Without clear guidance—in part due to the lack of high-quality evidence and clinical guidance from major medical societies—conflicting interpretations and recommendations have become mainstream.

To summarize:

The potential GI risks can be minimized by prescribing selective COX-2 inhibitors along with PPIs.

The risk of CV events may potentially be diminished by using lower-dose NSAIDs with shorter durations in at-risk patients.

With routine screening, the risk of nephrotoxicity among patients with stage-I and II renal dysfunction appears to be similar to that in the general population.

The effect of NSAIDs on bone-healing is so far unproven and remains a topic of debate.

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.