CHILDREN'S HOSPITAL MEDICAL CENTER
Grant: $225,000 - National Institutes of Health - May. 7, 2009
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Award Description: Osteoporosis is a major public health problem affecting over 10 million adults, primarily women. A key contributor to osteoporosis prevention is optimizing accrual of peak bone mass. Adolescence is a dynamic period for bond mass development as nearly 50% of mass is accrued primarily around puberty. Smoking, alcohol, & depression can negatively influence bone mass. Experimentation with substances begins and escalates in adolescence and in those more vulnerable, detrimental effects on health can occur across the lifespan. Depression also increases. There are differential rates and/or mobidity-mortality consequences by gender for substance use and depression with girls being more affected than boys. Compared to men, adult women have more difficulty in smoking cessation, are more likely to experience depression in cessation, and are more sensitive to negative consequences of alcohol. Further, depression is also linked with osteoporosisor low bone mass more so in women. No studies in adolescence have examined effects of substance use and depression on metabolic consequences, such as bone health. The R21 proposes to examine such issues in a biobehavioral conceptual model. Secondary analysis will be conducted in 264 girls (11-17 years) enrolled in a cross-sequential study for 3 annual visits (Dorn: PI; R01 DA16402). The sample reflects diversity in race/ethnicity (African-American 31.1%; Caucasian 63.3%) and social class. Retention is >90%. We included examination of alcohol use and analysis of frozen samples for cytokine activity and other hormones. Unique aims were added to examine the stress system and systemic inflammatory responses (cytokine activity) as potential mechanisms explaining the relationship of depression and substance use with bond health (bone mineral content). Aims are: (1) To examine characteristics of individual differences in developmental trajectories of bone health across 3 years by alcohol status, (2) To examine contextual effects of smoking and alcohol on the mediating pathway of stress system (HPA axis) activity on the relationship between symptoms of depression/anxiety and individual differences in developmental trajectories of bond health across 3 years, (3) To examine contextual effects of smoking and alcohol on the mediating pathway of the systemic inflammatory response (serus cytokine activity) on the relationship between depression/anxiety and individual differences in developmental trajectories of bone health across 3 years. Examining the impact of these factors has import for future intervention and prevention strategies in adolescence. The pathway to osteoporosis is multifactorial and begins early in life. Substance use and depression in adolescence may have long-term consequences for bond health (i.e., risk of osteoporotic fracture.
Project Description: This study has three aims: 1) examine characteristics of individual differences in developmental trajectories of bone health across 3 years by alcohol status, 2) examine the contextual effects of smoking and alcohol on the mediating pathway of stress system (HPA axis) activity on the relationship between symptoms of depression/anxiety and individual differences in developmental trajectories of bone health across 3 years, 3) examine the contextual effects of smoking and alcohol on the mediating pathway of the systemic inflammatory response (serum cytokine activity) on the relationship between symptoms of depression/anxiety and individual differences in developmental trajectories of bone health across 3 years. We hypothesize, first, that developmental trajectories will be different between those with alcohol behavior vs. those without. Girls with increasing alcohol use across time and higher frequency will have lower bond mineral accrual compared to girls with less exposure. Second, the stress system mediates the relationship between higher symptoms of depression/anxiety with bone accrual, such taht high HPA activity will result in lower accrual. This relationship will be stronger for both smoking and alcohol use groups. Third, the systemic inflammatory response (cytokine activity) will mediate the relationship between depression/anxiety and bone accrual. Again, the relationship will be stronger for both smoking and alcohol use groups. Currently, we are on target with out initial project goals. Year 1 and 2 Cytokine samples have been analyzed by the lab and we are in the process of cleaning the data and conducting preliminary analyses. Year 1 and 2 leptin samples are at the CTRC Core Lab for analysis. All Year 3 samples will be collected by November 2009 and then sent to the respective labs for analysis. After Year 3 samples are analyzed, we anticipate that all 3 aims can be accomplished.
Jobs Summary: The purpose of this R21 application is to examine potential biologic mechanisms (stress system and systemic inflammatory response) to explain the relationship between depression and substance use with bone health. The funding is allowing us to examine important biological relationships in adolescent females, but also allows retention of the Project Director and helped to create a position with the Division of Adolescent Medicine for a Data Manager. Stephanie Pabst, MEd, CCRP (Project Director) has a Masters degree in Nutrition Education and Food Science and she is also a Certified Clinic Research Coordinator. She has experience managing clinical research projects, including Smoking and Metabolic Complications in Adolescent Girls (R01 DA 16402) since August 2004. ms. Pabst is responsible for maintaining quality control of assays and serves as liaison for the status of processing of hormones at the core laboratory. She is also responsible for submitting appropriate forms to the IRB and monitoring requirements of communication with the IRB, the CTRC (formerly the GCRC) and NIDA. She will assist with budget management in consulation with Dr. Dorn and in collaboration with the Division of Adolescent Medicine business director. The project director will continue meeting with Dr. Dorn on a daily basis. In the data analysis and manuscript phase she will provide assistance with co-authoring manuscripts including serving as lead, tabling data, literature reviews, and references. Her 15% effort will allow me to retain her in this crucial position since funding for the parent project is in its no-cost extension year. Justin Bates (Data Manager) is Masters prepared and will work with the statistician in data management, cleaning data, creating summary variables, and performing general statistics. This model of a data managerworking with the statistician has provide the statistician with more of her time to conduct and/or consult on higher level statistics. The funding for this position allowed me to hire a Data Manager. Mr. Bates is on this project for 15% effort (Total jobs reported: 0)
Project Status: Less Than 50% Completed
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