SLR - December 2014 - Melissa Curry

The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing are Time-Dependent

Reference: Connizzo BK, Yannascoli SM, MD, Tucker JJ, Caro AC, Riggin CN, Mauck RL, Soslowsky LJ, Steinberg DR, Bernstein J. The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing are Time-dependent. Clin Orthop Relat Res. 2014 Aug;472(8):2433-9.

Scientific Literature Review

Reviewed By: Melissa Curry, DPM
Residency Program: St. Francis Hospital and Medical Center, Hartford, CT

Podiatry Relevance: Podiatric surgeons often prescribe NSAIDs for pain and inflammation control after an injury and/or surgery. Multiple studies document the detrimental effects NSAIDs have on bone repair, but effects on tendon healing are less clear. The reviewed article aims to biomechanically and histologically evaluate the effects of ibuprofen on tendons in both the early and late stages of repair.

Methods: Sixty-five male Sprague-Dawley rats were randomly assigned to one of the three groups: control repair, repair with early systemic ibuprofen administration, and repair with delayed systemic ibuprofen administration. All of the rats underwent bilateral supraspinatus detachment and repair surgeries. The two experimental groups were given liquid ibuprofen every 8-12 hours, with the early administration group receiving ibuprofen Days 0-7, and the late administration group days 8-14. The three groups were then evaluated at one, two, or four weeks. One shoulder of each rat was evaluated for histological purposes and the contralateral shoulder used for mechanical evaluation. Measurements of optical strain, tendon cross-sectional area, tensile strength, and fiber organization were evaluated. The comparisons made in this study were of the experimental groups to the control. Statistical significance was set at p?0.05.

Results: At four weeks post-surgery, the biomechanical results revealed that only the early ibuprofen delivery group when compared to the control group showed statistical significance between the tendon stiffness and modulus of elasticity. The late delivery group did not show statistical significance. For the histological parameters, there was a significant difference in fiber alignment in the control group but not in the ibuprofen groups. There was no significance with any relationship among cell density or cell shape. Both of the ibuprofen groups had significant blood vessel formation (79 percent hematoma formation in early group, 40 percent in the delayed group, 29 percent in the control group) at four weeks post-surgery.

Conclusions: The hypothesis of this study, that ibuprofen is detrimental to tendon healing when delivered early in the healing process but not when delivered in a delayed fashion, was supported by their results. It was suggested that the overall quality of the repair tissue was diminished and there was altered or delayed healing with early administration of ibuprofen. While other studies have found negative effects in the proliferative phase versus beneficial response in the remodeling phase, this study did not suggest an improved mechanical response with delayed administration. It instead supported the lack of detrimental effect. This study is a good stepping stone to further research that involves not only acute tendon injuries, but smaller level injuries that include overuse or repetitive fatigue injuries with low-level damage in the tendon. Ibuprofen is a widely used drug and caution should be taken when prescribing or suggesting this drug based on the timing of the injury/surgery. 

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