Postoperative Opioid Administration Inhibits Bone Healing in an Animal Model

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 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.

Will My Tibial Fracture Heal? Predicting Nonunion at the Time of Definitive Fixation Based on Commonly Available Variables

“…Pro [32] NSAID use at admission Pro [13,27] Con [17,35] NSAID use at discharge Pro [13,27] Con [17,35] Opioid use at admission Pro [12] Opioid use at discharge Pro [12] Human immunodeficiency virus Pro [24] Con [20] Hepatitis C None Diabetes Pro [13,21,27] ASA score Pro [16] Smoking status Pro [13,21,31,36] Con [29,35] Alcohol use Pro [10,13,21] AO classification Pro [30] Con [2,22] ISS score Pro [30] TRISS score Pro [30] ICU days None * Pro articles support a correlation between nonunion and the variable; Con articles show that the variable has no correlation with nonunion; GSW = gunshot wound; NSAID = nonsteroidal anti-inflammatory drug; ASA = American Society of Anesthesiologists; AO = Arbeitsgemeinschaft für Osteosynthesefragen; ISS = Injury Severity Score; TRISS = Trauma and Injury Severity Score; ICU = intensive care unit.…”

Effects of freshwater clam extract on fracture induced inflammation at early stage

“…Previous studies have investigated the medication influence on the callus formation and remodeling stages of bone fracture (13,14), while the influence of FCE on the acute stage of fracture is seldom studied. People who suffer from traumatic fracture are often admitted for further surgery, medical care of soft tissue, and administration of analgesics (1).…”

Updated Animal Models in Orthopaedic Research

“…Biomechanical testing and micro-CT analysis expressed that morphine administration leads to weaker callus and impedes callus maturation compared with controls. These fi ndings may change the post-op Orthopaedic analgaesic regimens [ 10 ]. Demirtas et al showed that Enoxaparin, Fondaparinux and Rivaroxaban used in thromboembolism prophylaxis caused no signifi cant changes in fracture healing in terms of clinical, radiological, and histopathological fi ndings with short term follow-up (21 days) in a standard closed femur fracture model in rats [ 11 ].…”

“…Cartilage cells (harvested from the talus of horses) were cultured and transduced with 10 5 AAV vg/cell prior to implantation. Arthroscopically created 15 mm full-thickness chondral defects were fi lled with naïve or gene-enhanced chondrocytes, in fi brin.…”