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The Journal of Bone and Joint Surgery (American) 86:116-123 (2004)
© 2004 The Journal of Bone and Joint Surgery, Inc.

Effect of COX-2-Specific Inhibition on Fracture-Healing in the Rat Femur

Karen M. Brown, MD1, Marnie M. Saunders, PhD1, Thorsten Kirsch, PhD2, Henry J. Donahue, PhD1 and J. Spence Reid, MD1

1 Department of Orthopaedics and Rehabilitation, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, P.O. Box 850, Hershey, PA 17033
2 Department of Orthopaedics, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201

Investigation performed at the Department of Orthopaedics and Rehabilitation, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the Arthritis Foundation, Central Pennsylvania Chapter. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Nonsteroidal anti-inflammatory medications have been shown to delay fracture-healing. COX-2-specific inhibitors such as celecoxib have recently been approved for human use. Our goal was to determine, mechanically, histologically, morphologically, and radiographically, whether COX-2-specific inhibition affects bone-healing.

Methods: A nondisplaced unilateral fracture was created in the right femur of fifty-seven adult male rats. Rats were given no drug, indomethacin (1 mg/kg/day), or celecoxib (3 mg/kg/day) daily, starting on postoperative day 1. Fractures were analyzed at four, eight, and twelve weeks after creation of the fracture. Callus and bridging bone formation was assessed radiographically. The amounts of fibrous tissue, cartilage, woven bone, and mature bone formation were determined histologically. Morphological changes were assessed to determine fibrous healing, callus formation, and bone-remodeling. Callus strength and stiffness were assessed biomechanically with three-point bending tests.

Results: At four weeks, only the indomethacin group showed biomechanical and radiographic evidence of delayed healing. Although femora from rats treated with celecoxib appeared to have more fibrous tissue than those from untreated rats at four and eight weeks, radiographic signs of callus formation, mechanical strength, and stiffness did not differ significantly between the groups. By twelve weeks, there were no significant differences among the three groups.

Conclusions: Postoperative administration of celecoxib, a COX-2-specific inhibitor, did not delay healing as seen at twelve weeks following fracture in adult rat femora. At four and eight weeks, fibrous healing predominated in the celecoxib group as compared with the findings in the untreated group; however, mechanical strength and radiographic signs of healing were not significantly inhibited.

Clinical Relevance: Many orthopaedists rely on narcotic analgesia for postfracture and postoperative pain, despite deleterious side effects and morbidity. Traditional nonsteroidal anti-inflammatory medications have been shown to delay fracture union. This effect may be smaller with COX-2-specific inhibitors.


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Letters to the Editor:

Read all Letters to the Editor

The Effect of COX-2 Inhibitors on Bone Healing
Noor M Gajraj
JBJS Online, 15 Jan 2004 [Full text]
Re: The Effect of COX-2 Inhibitors on Bone Healing
Per Aspenberg
JBJS Online, 17 Mar 2004 [Full text]
The Effect of NSAIDs on Fracture Healing
Catherine G Ambrose, et al.
JBJS Online, 17 Mar 2004 [Full text]
Dr. Brown responds to Drs. Ambrose and Aspenberg
Karen M. Brown
JBJS Online, 17 Mar 2004 [Full text]
Effect of COX-2 inhibitors on fracture healing
Benjamin Goldberg, M.D.
JBJS Online, 7 Jun 2004 [Full text]
Effect of Cox-2 Specific Inhibition on Fracture-Healing in the Rat Femur
Alberto D. Delgado-Martinez
JBJS Online, 30 Aug 2004 [Full text]