NSAIDs in Orthopaedics

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most used drugs in orthopaedics. They relieve pain, calm inflammation, and bring down fever, and they do all of this through a single shared mechanism: blocking the enzyme cyclooxygenase (COX) and so reducing prostaglandins.

The word "non-steroidal" simply distinguishes them from corticosteroids - they reduce inflammation without using a steroid. For the exam, the key idea is that the one mechanism explains everything: the benefits (less pain and inflammation) and the harms (stomach, kidney, heart and bleeding) all come from cutting prostaglandin production in different tissues.

Three themes run through this topic and are heavily examined: how COX-1 and COX-2 differ (and why that matters for side effects), the major harms and who is most at risk, and the two orthopaedic bone debates - whether NSAIDs slow fracture healing, and how the same drugs are used on purpose to prevent heterotopic ossification.

When a cell is injured, an enzyme called phospholipase A2 releases arachidonic acid from the cell membrane. Cyclooxygenase (COX) then converts arachidonic acid into prostaglandins and thromboxane. These molecules drive pain, inflammation, and fever, and they also do useful everyday jobs around the body.

NSAIDs block COX, so less arachidonic acid is turned into prostaglandins. The result is less pain, less inflammation, and less fever - but because the same prostaglandins protect the stomach, support kidney blood flow, and help platelets clot, blocking COX everywhere produces the familiar side effects.

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The two forms of the enzyme are the heart of this topic:

The high-yield message: non-selective NSAIDs block both forms, giving strong anti-inflammatory action but more gastric and bleeding problems. COX-2 selective drugs (coxibs) spare COX-1, so they cause less gastric ulceration and do not impair platelets - but they still affect the kidney and carry a recognised cardiovascular risk (thought to relate to an imbalance between prothrombotic thromboxane and protective prostacyclin).

Routes matter too. NSAIDs come as oral, intravenous or intramuscular (for example parecoxib and ketorolac for the immediate postoperative period), and topical preparations. Topical NSAIDs deliver drug to a superficial joint with much lower blood levels, so they are a sensible first step for localised osteoarthritis (for example of the knee or hand) in patients who cannot tolerate systemic NSAIDs.

Aspirin is the exception among NSAIDs and a favourite exam point. Whereas the other NSAIDs are reversible, competitive COX inhibitors, aspirin irreversibly acetylates the cyclooxygenase enzyme. Because a platelet has no nucleus and cannot synthesise new COX, a single dose abolishes that platelet's thromboxane production for the rest of its life — so the antiplatelet effect lasts the platelet lifespan (about 7 to 10 days) until enough new platelets are made, far longer than aspirin's short plasma half-life.

This pharmacology underlies two orthopaedic points:

• Stopping before surgery: where platelet function matters, antiplatelet-dose aspirin is typically stopped roughly a week beforehand to allow platelet turnover, whereas the reversible NSAIDs recover within a few half-lives of the drug being cleared.
• Venous thromboembolism (VTE) prophylaxis: low-dose aspirin is now an accepted chemoprophylaxis option after hip and knee arthroplasty and many lower-limb injuries. The randomised evidence is mixed — aspirin performed well in some trials (for example the EPCAT II trial, where aspirin after an initial course of an anticoagulant was non-inferior to continued anticoagulation), while a large trial (CRISTAL) favoured low-molecular-weight heparin for symptomatic VTE — but AAOS and other guidance now list aspirin alongside the anticoagulants, with the choice balancing VTE risk against bleeding.

Because NSAIDs are used as heterotopic ossification (HO) prophylaxis around the hip, the examiner expects you to be able to grade HO. The Brooker classification stages HO around the hip on an AP pelvic radiograph and is the system used in the prophylaxis trials below:

Grade I is common and usually asymptomatic; Grades III to IV are the clinically important end, restricting movement and occasionally fusing the joint. Prophylaxis (an NSAID course or low-dose radiotherapy) aims to keep an at-risk hip at Brooker 0 to I.

NSAIDs appear in nearly every part of orthopaedic practice and the exam. In clinic, they are the standard treatment for soft-tissue pain and osteoarthritis flares, and the choice between a systemic and a topical agent (and whether to add gastric protection) is everyday decision-making. Perioperatively, NSAIDs are a pillar of multimodal, opioid-sparing analgesia, but the surgeon must weigh bleeding, renal and cardiac risk against the benefits. In trauma and arthroplasty, two bone-specific issues dominate: the fracture-healing controversy (most surgeons avoid prolonged routine NSAIDs in fresh fractures with healing concerns) and heterotopic ossification prophylaxis after hip surgery. Examiners love NSAIDs precisely because the same mechanism is a benefit in one scenario and a hazard in another - so explaining the mechanism, then reasoning to the right decision, scores well.

• Osteoarthritis guidelines (for example AAOS in the US and NICE in the UK) recommend NSAIDs - topical NSAIDs first where the joint is superficial, then the lowest effective dose for the shortest time of an oral NSAID, with gastric protection or a COX-2 selective agent in those at gastrointestinal risk. The shared message is to individualise the choice to the patient's GI, renal and cardiovascular profile.
• Cardiovascular safety guidance (from medicines regulators in Europe, the UK and the US) is consistent: avoid or minimise NSAIDs in established cardiovascular disease, regard diclofenac and high-dose coxibs as higher cardiovascular risk, and treat naproxen and low-dose ibuprofen as relatively safer choices.
• Heterotopic ossification prophylaxis after hip and acetabular surgery is supported by randomised trials and meta-analysis: indomethacin, diclofenac and celecoxib all reduce heterotopic bone, with radiotherapy as the main alternative where NSAIDs are contraindicated. The choice between NSAID and radiotherapy varies by centre, patient risk, and the competing concern about fracture healing.
• Where guidance differs is mainly in the threshold for prophylaxis, the preferred agent and the duration of any course, rather than in the underlying pharmacology - the four big harms and the two-edged bone effect are universal.