Low-intensity pulsed ultrasound and nonsteroidal anti-inflammatory drugs have opposing effects during stress fracture repair

J Orthop Res. 2007 Dec;25(12):1559-67. doi: 10.1002/jor.20461.


Low-intensity pulsed ultrasound (LIPUS) and nonsteroidal anti-inflammatory drugs (NSAIDs) were used to treat stress fracture. Bilateral stress fractures were induced in the ulnas of 48 adult rats. Animals were divided into two groups (NSAID and VEH), and treated 5 days per week with celecoxib (5 mg/kg) mixed in a vehicle solution of polyethylene glycol and saline (NSAID) or vehicle alone (VEH). One-to-three hours following drug administration, all animals were treated with unilateral active-LIPUS and contralateral inactive-LIPUS. Equal numbers of ulnas from each drug group were histologically evaluated at 2, 4, and 8 weeks following induction of stress fracture. Neither LIPUS nor NSAID influenced bone resorption, but each had significant and opposite effects on intracortical bone formation rate. These effects indicate that LIPUS may be used to facilitate stress fracture repair whereas NSAID may delay tissue level repair of stress fractures. There was no interaction between LIPUS and NSAID, indicating that the beneficial LIPUS effect was not mediated by the cyclooxygenase-2 pathway. LIPUS accelerated stress fracture healing, whereas the NSAID delayed repair. When used in combination, the beneficial LIPUS effect was not impaired by the detrimental NSAID effect.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Bone Remodeling / drug effects*
  • Celecoxib
  • Combined Modality Therapy
  • Female
  • Fractures, Stress / drug therapy
  • Fractures, Stress / pathology
  • Fractures, Stress / therapy*
  • Models, Animal
  • Pyrazoles / adverse effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / adverse effects*
  • Ulna / pathology
  • Ulna Fractures / drug therapy
  • Ulna Fractures / pathology
  • Ulna Fractures / therapy*
  • Ultrasonic Therapy*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pyrazoles
  • Sulfonamides
  • Celecoxib