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Effect of Aspirin on Bone Healing in a Rabbit Ulnar Osteotomy Model

Lack, William D., MD1; Fredericks, Douglas, BS2; Petersen, Emily, DVM2; Donovan, Maureen, PhD3; George, Maya, MS3; Nepola, James, MD1; Smucker, Joseph, MD1; Femino, John E., MD1

doi: 10.2106/JBJS.L.00462
Scientific Articles
Supplementary Content

Background: Aspirin is frequently prescribed following orthopaedic surgery. Although there is substantial evidence that some nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with delayed bone healing, there have been few studies of the effects of aspirin on bone healing and, to our knowledge, none on the effects of physiologic dosages.

Methods: Following ulnar osteotomy, fifty-six rabbits were administered a placebo (nine rabbits), indomethacin (nine rabbits given 12.5 mg/kg daily), or aspirin at various doses and schedules (2.7 mg/kg daily for ten rabbits, 10 mg/kg daily for nine rabbits, 50 mg/kg twice daily for ten rabbits, and 100 mg/kg three times daily for nine rabbits). The aspirin doses were chosen to span the clinical dosing range. The indomethacin group served as a positive control and as a relative comparison with the effect of aspirin. Radiographs were obtained every two weeks and the animals were killed at eight weeks. Mechanical testing was performed on all rabbits except for six selected for histological evaluation.

Results: Aspirin delayed bone healing, as demonstrated radiographically and with mechanical testing, in a dose-dependent fashion at salicylate levels equivalent to those resulting from typical human dosing (low-dose aspirin). Receiver operating characteristic analysis demonstrated a plasma salicylate threshold above 20.7 μg/mL predicting delayed bone healing. This approximates a single human dose of 325 mg. Salicylate levels above this threshold were associated with delayed bone healing similar to that caused by indomethacin. Aspirin dosing frequency did not affect bone healing. Mechanical testing was highly predictive of radiographic healing. The interobserver reliability of radiographic assessment of healing at six and eight weeks (kappa = 0.83 and 0.79, respectively) compared favorably with interobserver reliability in previous studies assessing cortical bridging.

Conclusions: In a rabbit ulnar osteotomy model, aspirin delayed bone healing with a threshold equivalent to a human dose of 325 mg.

Clinical Relevance: The effect of aspirin on bone healing has not previously been studied within the typical clinical dosing range. Defining the relationship between aspirin and bone healing may improve fracture and osteotomy site healing as well as bone growth into implants.

1Department of Orthopaedics and Rehabilitation, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242. E-mail address for W.D. Lack:

2Bone Healing Research Lab, Old Farmstead Road, University of Iowa, Oakdale Research Building, Oakdale Campus, Iowa City, IA 52242

3Division of Pharmaceutics and Translational Therapeutics, University of Iowa, S219 PHAR, Iowa City, IA 52242

Copyright © 2013 by The Journal of Bone and Joint Surgery, Incorporated
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