• Jesse Chrastil, Christopher Sampson, Kevin B Jones, and Thomas F Higgins.
• Department of Orthopaedics, University of Utah, 590 Wakara Way, Salt Lake City, UT, 84108, USA, jesse.chrastil@hsc.utah.edu.
• Clin. Orthop. Relat. Res. 2014 Jun 1; 472 (6): 1964-71.

BackgroundOpioid pain medications are the basis for analgesia after orthopaedic injuries and procedures. However, opioids have many adverse effects, including opioid-induced androgen deficiency.Questions/PurposesWe evaluated the occurrence and affect of opioid-induced androgen deficiency on osseous union and its ability to be reversed. Additional focus was placed on its perioperative onset and its duration in an orthopaedic animal model.MethodsA femoral osteotomy was created in 75 Sprague-Dawley rats. Postoperatively, animals were randomized into three treatment groups: control, morphine, and morphine plus testosterone. Testosterone levels were recorded preoperatively and at 48 hours, 4 weeks, and 8 weeks postoperatively. Some animals were euthanized at 4 weeks and others at 8 weeks postoperatively. Histology and micro-CT scans were used to evaluate callus. Three-point bend testing was performed to evaluate callus strength.ResultsSerum testosterone levels in the morphine group showed decreased baseline levels of 2.2 ng/mL, 1.4 ng/mL, and 1.4 ng/mL (p < 0.001), whereas the morphine plus testosterone supplementation group showed increased serum levels at 41.7 ng/mL, 11.8 ng/mL, and 19.8 ng/mL (p < 0.001) compared with control animals (3.3 ng/mL, 5.8 ng/mL, 5.2 ng/mL) at 48 hours, 4 weeks, and 8 weeks, respectively. Compared with control animals, histology and micro-CT showed an impedance of callus maturation in the two experimental groups. Morphine-treated animals showed reduction in callus strength at 8 weeks (30% of the contralateral unfractured femur strength compared with 49% seen in the control animals at 8 weeks; p = 0.048); this finding was not fully reversed by testosterone supplementation (33% of the contralateral femur strength; p = 0.171).ConclusionsOpioid-induced androgen deficiency occurred in this orthopaedic animal model. Although we previously showed that morphine inhibits callus maturation, the current study did not show a rescue of the morphine-treated animals with testosterone supplementation in either morphologic or mechanical testing. Testosterone suppression associated with opioid administration occurred almost immediately (within 48 hours) and was suppressed continually throughout the 8-week duration of study.Clinical RelevanceOpioid-induced androgen deficiency occurs during the perioperative orthopaedic period. Although its clinical relevance remains unknown, further evaluation is needed to determine if supplementation is warranted during the perioperative period.

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