Excessive alcohol consumption resulting in disease and increasing the risk of traumatic injury contributes significantly to the public health burden in the United States. The skeleton is a significant target organ for the deleterious effects of alcohol because it suffers alcohol-related damage in two distinct ways; both directly from excessive alcohol consumption, and indirectly due to the increased risk for traumatic injury caused by alcohol drinking behavior. Fracture nonunion is a condition where a bone fracture injury fails to heal normally requiring surgical intervention and alcohol consumption has been shown to contribute to the risk for this serious clinical complication. Currently, clinical options for patients with a non-healing fracture such as surgical grafting of autogenous or de-mineralized bone preparations each have serious limitations. Obtaining autogenous bone graft is effectively a separate surgical procedure at risk for another set complications and de-mineralized bone preparations are unreliable. Normal fracture healing is a regenerative process that utilizes stem cells to rebuild new bone at the injury site. However, we currently do not understand how alcohol affects the activity of stem cells at the fracture site. We believe that alcohol consumption negatively affects stem cell activity that is critical to successful fracture repair. The goal of this investigation is to understand if alcohol affects mesenchymal stem cell differentiation toward chondrocytes following bone fracture injury and if decreased MSC to chondrocyte differentiation may underlie alcohol related inhibition of fracture callus formation and fracture union. Because young people are more likely to suffer traumatic injury, it is important to understand the effects of episodic or binge drinking on fracture repair as binge alcohol consumption is the prevalent pattern of alcohol drinking in both adolescent and young adult populations. The fact that about 40% of the orthopaedic inpatient population is intoxicated at the time of hospital admission underscores the significance of understanding the impact of binge alcohol consumption on the fracture repair process. We believe that the data obtained from this proposal will lead to a better understanding of why alcohol consumption negatively impacts the fracture repair process and how we can improve the prognosis for orthopaedic trauma patients with bone fracture injuries complicated by concomitant alcohol consumption though the use of stem cell technology.
The research described in this application is relevant to public health in the United States because the consumption of alcohol-containing beverages increases the risk for both accidents resulting in skeletal injury and serious clinical complications associated with these injuries, including fracture nonunion, which greatly increases patient morbidity and mortality following a fracture injury. The fact that these alcohol-associated injuries are most likely to occur in our adolescent and young adult populations increases the need for research in the area of alcohol consumption and orthopaedic injury to allow these persons to resume a productive life as citizens of our country. An understanding of the reasons why bone fracture injuries are less likely to heal normally in alcohol-intoxicated patients may allow us to use different treatment strategies for this subset of injured persons to increase the odds that they may recover fully from their injuries.
| Natoli, Roman M; Yu, Henry; Meislin, Megan Conti-Mica et al. (2018) Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro. J Orthop Surg Res 13:101 |
| Bratton, Anthony; Eisenberg, Joshua; Vuchkovska, Aleksandra et al. (2018) Effects of Episodic Alcohol Exposure on BMP2 Signaling During Tibia Fracture Healing. J Orthop Trauma 32:288-295 |
