Antioxidant Therapy Attenuates Deficient Bone Fracture Repair Associated With Binge Alcohol Exposure

Abstract

Objectives Alcohol consumption is a known risk factor for traumatic injuries of all types and has been shown to produce detrimental effects on bone metabolism. While the mechanisms responsible for these detrimental effects are not well characterized, oxidative stress from alcohol exposure appears to play a central role. This study was designed to examine the effect of a short-term binge alcohol consumption pattern on fracture repair and the effect of an antioxidant, N-acetylcysteine, on fracture healing following binge alcohol consumption. Methods One hundred forty-four (144) adult male Sprague Dawley rats underwent unilateral closed femur fracture after injection of either saline or alcohol to simulate a binge alcohol cycle. Animals in the antioxidant treatment group received daily N-acetylcysteine following fracture. Femurs were harvested at 1, 2, 4 and 6 weeks following injury and underwent biomechanical testing and histological analysis. Results Binge alcohol administration was associated with significant decreases in biomechanical strength at one and two-week time points with a trend toward decreased strength at four and six-week time points as well. Alcohol-treated animals had less cartilage component within the fracture callus and healed primarily by intramembranous ossification. Administration of N-acetylcysteine in alcohol-treated animals improved biomechanical strength to levels comparable to the control animals and was associated with increased endochondral ossification. Conclusions Our results indicate that binge alcohol alters the quality of fracture healing following a traumatic injury and that concurrent administration of an antioxidant is able to reverse these effects.

Mesenchymal Stem Cells Facilitate Fracture Repair in an Alcohol-Induced Impaired Healing Model

“…While MSC homing to the site of fracture has been demonstrated [21], no studies to our knowledge have examined this phenomenon in a setting of fracture healing that was impaired by the clinically relevant co-morbidity of pre-injury alcohol exposure. In a study utilizing a similar alcohol exposure/fracture injury model in rats, our laboratory demonstrated that alcohol caused an impairment of external callus formation and endochondral ossification at 14 days following injury[7]. This was consistent with our preliminary observations in the mouse.…”

“…ethanol/saline solution) resulting in a blood alcohol content (BAC) of approximately 200 mg/dl at the time of injury. We developed the current model of 2 week binge-like alcohol administration to mimic a similar binge drinking pattern commonly associated with orthopaedic trauma patients [12] – the weekend drinker – and previous work in our lab demonstrated that this alcohol administration paradigm leads to inhibition of bone fracture repair in mice and rats [23, 24]. One hour after the final alcohol dose, the mice underwent a modified, stabilized mid-shaft tibia fracture injury as previously described[25].…”

“…Impaired fracture healing related to alcohol exposure is a pathophysiologically relevant alternative for studying fracture repair. Preclinical studies have demonstrated that alcohol exposure impedes fracture callus composition and biomechanical strength[7] and modulates the immunoinflammatory response to blunt orthopaedic trauma[8]. …”

Ketorolac Administration Does Not Delay Early Fracture Healing in a Juvenile Rat Model

“…On the basis of a power analysis of prior studies investigating inhibitory effects of alcohol in fracture repair in our laboratory, this number of subjects is sufficient to avoid a type II error. 46 Animals were randomly assigned to receive intraperitoneal (IP) ketorolac (5 mg/kg) or isotonic saline control for 7 days (ketorolac n=8, saline n=7), 14 days (ketorolac n=8, saline n=7), or 21 days (ketorolac n=8, saline n=7) postoperatively. The animals were fed ad libitum during the study.…”

L’alcool : une drogue licite aux conséquences bucco-dentaires non négligeables

“…Sur le plan général, l' abus d' alcool a un rôle néfaste sur la santé osseuse et représente un facteur de risque d'ostéoporose, de fractures et de non-consolidation après fractures [39][40][41][42]. Bien que les mécanismes par lesquels ses effets sur le métabolisme osseux et la balance entre résorption et apposition autour d' un implant (quel qu' il soit) ne soient pas complètement élucidés [43], on sait que sa consommation est associée à des déficiences du système immunitaire qui perturbent le remaniement des tissus osseux péri-implantaires, mettant en péril l' ostéo-intégration [44,45] et favorisant la péri-implantite [46].…”