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Background: Opioid pain medications are the basis for analgesia after orthopaedic injuries and procedures. However, opioids have many adverse effects, including opioid-induced androgen deficiency., Questions/purposes: We 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., Methods: A 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., Results: Serum 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)., Conclusions: Opioid-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 Relevance: Opioid-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.

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 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 = 0.048) reduction in callus strength in morphine-treated animals 8 weeks postoperatively compared with controls. Radiographic and histological analysis showed delayed callus maturation and lack of remodeling in the morphine group compared with control animals at 8 weeks. Micro-CT analysis expressed remodeling and resorption as a decrease in callus volume over the two time points. The control group had significant levels of resorption decreasing 29% (p = 0.023) over the 4-week to 8-week time interval. Morphine administration inhibited callus resorption and remodeling with only a 13% decrease (p = 0.393) in callus volume comparing these time points. The callus inhibition associated with morphine administration was not as evident in the acute, 4-week time setting., Conclusions: Morphine administration inhibited callus strength in this animal model. This finding is likely consistent with the observation that the callus and healing bone appear to have a decreased rate of maturation and remodeling seen at 8 weeks., Clinical Relevance: This study identifies that administration of an opioid pain medication leads to weaker callus and impedes callus maturation compared with controls. These findings may provide the impetus to alter our current orthopaedic analgesic gold standard toward more multimodal and opioid-limiting pain control regimens.