More than 25 million people suffer from osteoporosis in the United States. Osteoporosis is a complex disease of aging that is likely to be attributable to several as yet unidentified genetic and environmental influences. Unlike other tissues in the body that cause to grow after adolescence, bone tissue is continuously growing and resorbing in a process known as remodeling. During most of adult life, growth and resorption rates are in equilibrium. At older ages, however, the rate of resorption outpaces the rate of new bone formation. The result is a progressive loss of bone mineral density leading to increased bone fragility. The overall objective of this study is to collect preliminary data on bone turnover markers in 500 adult family members participating in the Fels Longitudinal Study in order to determine the nature of genetic effects on these traits using quantitative genetic analysis. The results of this one-year pilot grant will be used as the foundation for a larger R01 application analysis. The results of this one-year pilot grant will be used as the foundation for a larger R01 application with a primary research goal of isolating and locating specific genes influencing normal variation in bone mineral density and related phenotypes. For the proposed pilot study, several markers of bone turnover will be assayed from stored serum samples using commercially available kits. These assays include bone-specific alkaline phosphatase, osteocalcin, pyridinoline crosslinks, total deoxypyridinoline crosslinks, C-terminal propeptide of type I collagen and YKL-40. All of these measures of bone loss, yet little research has focused on understanding the genetic basic of phenotypic variation in these traits. The working hypothesis of the proposed study is that genetic factors influence normal quantitative variation in bone turnover. And further, genetic effects on measures of bone turnover ultimately influences bone mineral density and subsequent risk for osteoporosis.
