Excessive alcohol consumption resulting in disease and increasing the risk of traumatic injury contributes significantly to the public health burden i the United States. The skeleton is a significant target organ for the deleterious effects of alcoho 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 non-union 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 patints 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. Thus, stem cell-based strategies for non-union may offer a new approach to resolving this challenging clinical problem. However, we currently do not understand how alcohol affects either endogenous or exogenous recruitment of stem cells to the site of fracture injury, limiting the potential of stem cell technology in alcohol abusing patients. The goal of this investigation is to understand if alcohol affects mesenchymal stem cell recruitment following bone fracture injury and if decreased recruitment may underlie alcohol related inhibition of fracture injury repair. Because young people are more likely to suffer traumatic injury, it is important to understand the effects of periodic or binge drinking on fractue 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 application 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. 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 treatmen strategies for this subset of injured persons to increase the odds that they may recover fully from their injuries.
|Hoscheit, Matthew; Conner, Grant; Roemer, James et al. (2016) Burn Injury Has Skeletal Site-Specific Effects on Bone Integrity and Markers of Bone Remodeling. J Burn Care Res 37:367-378|
|Roper, Philip M; Abbasnia, Pegah; Vuchkovska, Aleksandra et al. (2016) Alcohol-related deficient fracture healing is associated with activation of FoxO transcription factors in mice. J Orthop Res 34:2106-2115|
|Driver, Joseph; Weber, Cynthia E; Callaci, John J et al. (2015) Alcohol inhibits osteopontin-dependent transforming growth factor-?1 expression in human mesenchymal stem cells. J Biol Chem 290:9959-73|
|Lauing, Kristen L; Sundaramurthy, Sumana; Nauer, Rachel K et al. (2014) Exogenous activation of Wnt/?-catenin signaling attenuates binge alcohol-induced deficient bone fracture healing. Alcohol Alcohol 49:399-408|