The detrimental effects of systemic Ibuprofen delivery on tendon healing are time-dependent

Clin Orthop Relat Res. 2014 Aug;472(8):2433-9. doi: 10.1007/s11999-013-3258-2.


Background: Current clinical treatment after tendon repairs often includes prescribing NSAIDs to limit pain and inflammation. The negative influence of NSAIDs on bone repair is well documented, but their effects on tendon healing are less clear. While NSAIDs may be detrimental to early tendon healing, some evidence suggests that they may improve healing if administered later in the repair process.

Questions/purposes: We asked whether the biomechanical and histologic effects of systemic ibuprofen administration on tendon healing are influenced by either immediate or delayed drug administration.

Methods: After bilateral supraspinatus detachment and repair surgeries, rats were divided into groups and given ibuprofen orally for either Days 0 to 7 (early) or Days 8 to 14 (delayed) after surgery; a control group did not receive ibuprofen. Healing was evaluated at 1, 2, and 4 weeks postsurgery through biomechanical testing and histologic assessment.

Results: Biomechanical evaluation resulted in decreased stiffness and modulus at 4 weeks postsurgery for early ibuprofen delivery (mean ± SD [95% CI]: 10.8 ± 6.4 N/mm [6.7-14.8] and 8.9 ± 5.9 MPa [5.4-12.3]) when compared to control repair (20.4 ± 8.6 N/mm [16.3-24.5] and 15.7 ± 7.5 MPa [12.3-19.2]) (p = 0.003 and 0.013); however, there were no differences between the delayed ibuprofen group (18.1 ± 7.4 N/mm [14.2-22.1] and 11.5 ± 5.6 MPa [8.2-14.9]) and the control group. Histology confirmed mechanical results with reduced fiber reorganization over time in the early ibuprofen group.

Conclusions: Early administration of ibuprofen in the postoperative period was detrimental to tendon healing, while delayed administration did not affect tendon healing.

Clinical relevance: Historically, clinicians have often prescribed ibuprofen after tendon repair, but this study suggests that the timing of ibuprofen administration is critical to adequate tendon healing. This research necessitates future clinical studies investigating the use of ibuprofen for pain control after rotator cuff repair and other tendon injuries.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Biomechanical Phenomena
  • Disease Models, Animal
  • Drug Administration Schedule
  • Elastic Modulus
  • Ibuprofen / administration & dosage*
  • Ibuprofen / toxicity*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tendon Injuries / pathology
  • Tendon Injuries / physiopathology
  • Tendon Injuries / surgery*
  • Tendons / drug effects*
  • Tendons / pathology
  • Tendons / physiopathology
  • Tendons / surgery*
  • Tenotomy*
  • Time Factors
  • Wound Healing / drug effects*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Ibuprofen