NSAIDs in Orthopedic Pain: New Expert Consensus Sets Clear Prescribing Rules

Non-steroidal anti-inflammatory drugs, or NSAIDs, have long been a cornerstone of pain management in orthopedics, yet prescribing practices around them remain stubbornly inconsistent. Now, a new Delphi consensus promoted by the Italian Society of Orthopedics and Traumatology (SIOT) has produced a set of evidence-informed recommendations designed to bring clarity to how these drugs should be used across the full spectrum of orthopedic pain scenarios. The consensus, published in Frontiers in Pain Research, involved a rigorous two-round modified Delphi process coordinated by a methodologist, drawing on the expertise of orthopedic surgeons, anesthesiologists, and pharmacologists affiliated with SIOT. The result is a clinically actionable framework that addresses NSAID mechanisms of action, perioperative pain management in elective surgery, traumatic pain, and both non-oncological and oncological pain.

The Delphi method, originally developed at the RAND Corporation in the early 1950s, is a structured, iterative consensus-building technique designed to elicit and aggregate expert opinion on topics where robust empirical evidence is lacking or incomplete. It relies on four core principles: anonymity of participants, iterative questioning across successive rounds, controlled feedback provided between rounds, and statistical aggregation of group responses. In the health sciences, the method has gained widespread adoption for the development of clinical guidelines and recommendation statements, particularly in contexts where randomized controlled trial evidence is unavailable or difficult to obtain. The SIOT consensus applied this methodology to NSAID prescribing in orthopedics, a field where significant variability persists in practice and adherence to existing guidelines.

The consensus process began with a scientific board of seven members—six clinicians and one methodologist—who defined the clinical questions, identified key topics, and conducted a systematic literature review using PubMed/MEDLINE. The board proposed twenty statements spanning four domains, which were then submitted to a broader expert panel of twenty-eight members for evaluation using a six-point Likert scale. Consensus was defined as at least seventy-five percent of ratings concentrating within a single tertile of ascending relevance. In the first round, held on twenty-nine October 2025, twelve statements reached consensus. Six revised statements reached consensus in the second round, held on three December 2025, while two were eliminated because of persistent opinion dispersion.

Among the most significant recommendations to emerge from the process is the endorsement of short-cycle NSAID therapy, limited to cycles of a maximum of seven to ten days, within a multimodal analgesia approach. The panel agreed that because renal, cardiovascular, and gastrointestinal risks are closely related to NSAID dose and duration of treatment, current recommendations suggest that NSAIDs may be considered relatively safe when prescribed at the lowest effective dose for a period not exceeding ten days. Multimodal analgesia combinations incorporating NSAIDs have been established as an effective pain management strategy in several studies, particularly in the perioperative setting, and the consensus reinforces this framework as the standard of care for effective and opioid-sparing pain management in orthopedics.

The consensus also supports the use of symptomatic slow-acting drugs for osteoarthritis, known as SYSADOAs, to reduce NSAID consumption in patients with osteoarthritic pain. A recent meta-analysis confirmed the efficacy of SYSADOAs in osteoarthritis, with evidence supporting their NSAID-sparing effect in this clinical context. The panel agreed that when administered as part of conservative treatment strategies for osteoarthritic pain, SYSADOAs can help reduce the use of NSAIDs, offering a pharmacological alternative that may improve long-term safety profiles for patients requiring sustained pain management. This recommendation is particularly relevant given that osteoarthritis is among the most prevalent musculoskeletal disorders worldwide and one of the leading causes of chronic pain and disability.

In the domain of traumatic pain, the consensus reached agreement on two statements with important clinical implications. The panel recommended NSAIDs perioperatively in frail fracture patients within multimodal analgesia protocols to reduce opioid intake and limit the onset of complications, including delirium. Evidence from recent randomized controlled trials supports this approach: in one trial conducted in one hundred thirty-two patients aged sixty-five years or older undergoing hip fracture surgery, the prevalence of postoperative delirium was significantly lower in the anti-inflammatory bundle group compared with the placebo group. In another trial, the combination of oral acetaminophen and intravenous ketorolac was a viable alternative to opioid-based pain management in closed tibial shaft fractures treated with intramedullary nailing, decreasing opioid consumption without affecting pain scores or union rates.

The panel also affirmed that short-term administration of an NSAID, defined as less than ten to fifteen days, in the postoperative period and upon discharge of a patient operated on for a fracture is not associated with a significant risk of pseudoarthrosis. Several studies and meta-analyses have shown that short-term NSAID use does not significantly affect bone healing rates or increase the incidence of delayed union. However, the consensus was refined in the second round to establish that regular use of NSAIDs should be limited in patients at risk of developing stress fractures. Emerging evidence suggests that NSAIDs may inhibit remodeling within cortical bone, which could lead to increased bone density with extended use in a similar fashion as antiresorptive medications, potentially increasing the risk of stress fractures in physically active populations.

A particularly notable recommendation identifies ketoprofen lysine salt as having a favorable risk-benefit profile for postdischarge pain management, especially for treatments lasting up to seven to fourteen days. The efficacy of ketoprofen for acute postoperative pain has been supported by a Cochrane review, and evidence from multiple clinical trials demonstrates that ketoprofen achieves the highest ratio between anti-inflammatory and analgesic effects among non-selective NSAIDs. A recent review outlined the advantages of ketoprofen lysine salt versus ketoprofen acid in terms of greater gastric tolerability and quicker onset of action. Furthermore, a large epidemiological study derived from a database of eight and a half million new NSAID users identified seventy-nine thousand five hundred fifty-three cases of acute myocardial infarction, finding that ketoprofen appeared to be the most widely used drug with the lowest cardiovascular risk among the NSAIDs studied.

The consensus emphasizes individualized NSAID selection based on cardiovascular, renal, and antiplatelet risk factors. The panel agreed that the presence of cardiovascular risk factors or pathology in patients with chronic orthopedic pain requires a carefully personalized choice of NSAID, and that the presence of impaired renal function requires the same individualized approach with systematic monitoring of the patient’s hydration status. Nephrotoxicity risk is elevated in elderly patients, hypovolemia, high-dose NSAID exposure, concurrent use of vasoconstrictors, and concomitant therapy with renin-angiotensin-aldosterone system inhibitors or diuretics. The panel also highlighted that the potential interference of NSAIDs with platelet aggregation processes requires particular attention in patients receiving acetylsalicylic acid therapy, as NSAIDs with long half-lives can compete with aspirin for COX-1 binding, potentially reducing its antiplatelet efficacy.

The pathophysiology underlying NSAID analgesia involves the inhibition of the cyclooxygenase family of enzymes, which are involved in the formation of prostaglandins in both the periphery and the central nervous system. Prostaglandin E2 promotes the inflammatory response in the periphery and the sensitized neuronal state in the dorsal horn of the spinal cord. At peripheral sites of inflammation, the activation of PGE2 receptors on nociceptor terminals causes neuronal depolarization and sensitization, facilitating their activation by other inflammatory mediators such as bradykinin. In response to nociceptive input, COX-2 expression is upregulated in several areas of the central nervous system, and PGE2 is released in the dorsal horn, where it acts both pre- and postsynaptically to contribute to central sensitization. Beyond cyclooxygenase inhibition, NSAIDs may also modulate additional inflammatory pathways and nociceptive processing, and there is evidence that they act centrally in structures such as the periaqueductal gray and the rostral ventromedial medulla to activate descending inhibitory pain pathways.

The SIOT consensus provides evidence-informed, clinically actionable recommendations for NSAID use across the principal orthopedic pain scenarios, aiming to improve prescribing appropriateness and patient safety in routine practice. The engagement of specialists representing diverse Italian clinical hospitals facilitated the synthesis of complementary perspectives and heterogeneous clinical experiences. The recommendations proposed through this document, founded upon scientific evidence and informed by clinical practice, constitute a resource for delivering pragmatic guidance readily translatable into routine clinical care. As the burden of musculoskeletal pain continues to grow globally, with osteoarthritis imposing an increasing cost at both individual and societal levels, consensus documents such as this one represent an important step toward standardizing care and optimizing outcomes for the millions of patients who rely on NSAIDs for pain relief every day.

Subject of Research: Use of NSAIDs in orthopedic pain management: a Delphi consensus promoted by the Italian Society of Orthopedics and Traumatology (SIOT)

Article Title: Use of NSAIDs in orthopedic pain management: a Delphi consensus promoted by the Italian Society of Orthopedics and Traumatology (SIOT)

Article References: Tranquilli Leali, P., Di Martino, A., Mercurio, M., Spinelli, M. S., Coluzzi, F., Gargano, F., Berti, L., Rivera, F., Grossi, P., Solarino, G., Urbani, A., Scaglione, F., & Randelli, P. S. (2026). Use of NSAIDs in orthopedic pain management: a Delphi consensus promoted by the Italian Society of Orthopedics and Traumatology (SIOT). Frontiers in Pain Research, 7, Article 1944515. https://doi.org/10.3389/fpain.2026.1944515

Image Credits: AI Generated

DOI: 10.3389/fpain.2026.1944515

Keywords: NSAIDs, orthopedic, pain, management, Delphi, consensus, promoted, Italian, Society, Orthopedics, Traumatology, SIOT