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Non-union and use of proton pump inhibitors in the treatment of femoral and tibial shaft fractures: a nested case–control study



Proton pump inhibitors (PPIs) are one of the most frequently used drugs worldwide. Previous research has shown that they could increase the risk of fracture and interfere with the fracture healing process. In this study, we analyzed the effect of PPIs on the risk of fracture non-union in patients with femoral and tibial shaft fractures.


A case–control study was conducted at our institution, including a total of 254 patients who underwent fixation surgery for a femoral or tibial shaft fracture between January 2012 and December 2017. We defined cases as patients who experienced a delayed union (case group A; n = 44), or non-union (cases group B; n = 12). Cases were matched by age, sex, and fractured bone, to 144 controls who did not experience delayed fracture union and did not require further procedures. A conditional logistic regression analysis was performed adjusted to potential confounders, and to the proportion of days covered (PDC) with PPIs.


Adjusted ORs (95% CI) for undergoing a nail dynamization following a tibial or femoral shaft fracture were 1.38 (0.70–2.65) for any use PPIs. Patients with a longer PPI treatment courses (PDC ≥ 0.5) had an adjusted OR of 1.86 (0.70–4.76) for undergoing nail dynamization when compared with controls. Contrastingly, patients with a PDC < 0.5 had an adjusted OR of 1.03 (0.43–2.48). The adjusted OR (95% CI) for undergoing additional surgical procedures due to non-union was 4.5 (0.62–32.8) for any use of PPIs, and 12.3 (1.9–81.0) in patients with a PDC ≥ 0.5.


A prolonged use of PPIs use was associated with a higher risk of fracture non-union in tibial and femoral shaft fractures.

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We thank the patients who took part in this study and the information provided by all the authors.


The authors received no special funding for this study. Approval from the ethical committee of our hospital was obtained to carry out the study.

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Correspondence to Iskandar Tamimi.

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Fernandez-Arroyabe, N., García-Meléndez, G., De Castro-Almeida, A.R. et al. Non-union and use of proton pump inhibitors in the treatment of femoral and tibial shaft fractures: a nested case–control study. Eur J Orthop Surg Traumatol (2021).

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  • Proton pump inhibitors
  • Bone healing
  • Non-union
  • Pseudoarthrosis
  • Tibia
  • Fracture