Effects of Acute and Chronic Alcohol Intoxication on Fracture Healing in Orthopaedic Trauma Patients: Effects on Mesenchymal Stem Cell Lineage Differentiation Required for Fracture Repair

7. PROJECT SUMMARY/ABSTRACT
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 exploratory investigation is to examine the effects of
alcohol consumption on stem cell differentiation potential, using clinical samples obtained from
alcohol-intoxicated orthopaedic trauma patients at the time of surgery. This will be the first
examination of whether alcohol consumption at the time of injury affects the ability of stem cells to
heal a bone fracture. The study will also examine a potential mechanism that causes alcohol to inhibit
stem cells from differentiating into cell types required for normal fracture repair. 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 targeted therapeutic regimens.

Grant Number: 5R21AA029993-02
NIH Institute/Center: NIH
Principal Investigator: JOHN CALLACI