Postoperative Opioid Administration Inhibits Bone Healing in an Animal Model
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Clin Orthop Relat Res (2013) 471:4076–4081 DOI 10.1007/s11999-013-3232-z
A Publication of The Association of Bone and Joint Surgeons®
BASIC RESEARCH
Postoperative Opioid Administration Inhibits Bone Healing in an Animal Model Jesse Chrastil MD, Christopher Sampson BS, Kevin B. Jones MD, Thomas F. Higgins MD
Received: 14 March 2013 / Accepted: 5 August 2013 / Published online: 17 August 2013 Ó The Association of Bone and Joint Surgeons1 2013
Abstract Background The current mainstay of orthopaedic pain control is opioid analgesics but there are few studies in the literature evaluating the effects of opioids on bone healing. Questions/purposes The purpose of this study was to use a rat fracture model to evaluate the effects of opioid administration on osseous union in the acute (4 weeks) and subacute (8 weeks) setting in an operatively stabilized fracture. We asked the following question: does morphine administration alter (1) fracture callus strength; (2) callus
Funding for this study was provided by an Orthopaedic Research and Education Foundation’s (OREF)/Synthes Resident Research Project Grant and a departmental grant from the Sherman S. Coleman Resident Research Fund. Synthes Research Project Support donated surgical supplies/instruments. One of the authors (KBJ) receives career development support from the National Cancer Institute (K08CA138764). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. All work was performed at the University of Utah campus, Salt Lake City, UT, USA. J. Chrastil (&), K. B. Jones, T. F. Higgins Department of Orthopaedics, University of Utah, 590 Wakara Way, Salt Lake City, UT 84108, USA e-mail: [email protected]; [email protected] C. Sampson School of Medicine, University of Utah, Salt Lake City, UT, USA
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volume and formation; and (3) morphology and early remodeling to final osseous union? Methods A 0.4-mm femoral osteotomy gap was created in 50 Sprague-Dawley rats using an established model. Postoperatively, rats were randomized to control versus morphine-treated study groups. Equal numbers of rats from each group were euthanized at 4 weeks and 8 weeks postoperatively. Three-point bend biomechanical testing was performed to evaluate postoperative callus strength. Micro-CT scans and histological analyses were used to evaluate postoperative callus volume and formation, morphology, and features of early remodeling. Results Biomechanical testing identified a statistically significant (p = 0.04
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