• NSAIDs;
  • Fracture healing;
  • Opioids;
  • Confounding



To analyze the relationship between nonunion of humeral shaft fractures and nonsteroidal antiinflammatory drug (NSAID) exposure in older adults.


A cohort of 9,995 patients with humeral shaft fractures was identified using diagnosis and procedure codes from a Medicare database of >500,000 patients. Prescription NSAID as well as prescription opioid use was assessed from pharmacy claims data for 3 30-day periods immediately after the initial fracture. Nonunion was defined by the presence of procedure codes for repair of nonunion 90–365 days after the index fracture. We examined the association between NSAIDs and nonunion using multivariate Cox proportional hazards models.


Of the 9,995 humeral shaft fractures, 105 patients developed nonunions (1.1%), and 1,032 (10.3%) were exposed to NSAIDs in the 90 days after fracture. NSAID exposure within the first 90 days was significantly associated with nonunion (relative risk [RR] 3.7, 95% confidence interval [95% CI] 2.4–5.6). When indicators for exposure to NSAIDs during each of the 3 30-day windows were placed into the same multivariate model, only the period 61–90 days postfracture was significantly associated with nonunion (RR 3.9, 95% CI 2.0–6.2). We observed a similar association between opioids and nonunion, with exposure to opioids between 61 and 90 days associated with nonunion (RR 2.7, 95% CI 1.5–5.2), but exposure to opioids during neither of the 2 earlier 30-day periods significantly associated with nonunion.


We found that exposure to nonselective NSAIDs or opioids in the period 61–90 days after a humeral shaft fracture was associated with nonunion. Although these associations may be causal, they are more likely to reflect the use of analgesics by patients with painful nonhealing fractures.