The proposed study is designed to provide transformative knowledge for the first time, about how childhood history of environmental lead (Pb) exposure impacts combined bone and musculature (CBAM) health later in life among African American women. While blood lead concentrations (PbB) in the general population of the U.S. have declined since the discontinuation of Pb as a gasoline additive, Pb sequestered in bone continues to be a source of internal exposure for millions of women, especially minorities exposed to moderate to high levels of Pb during their formative years. African-American women have lower dietary calcium, more likely to be lactose intolerant, vitamin D deficient and have environmental Pb exposure that is associated with lower birth weight, poor postural balance and falls. Therefore, combined risks of nutritional status and Pb exposure potentially compromise several bone and muscular parameters. These include bone mineral content (BMC), bone mineral density (BMD), lower birth weight affecting postnatal bone growth and structural integrity of CBAM. Lower structural integrity suggests reduced ability of CBAM to absorb externally applied dynamic loads thereby increasing susceptibility to bone fracture. The energy absorption or damping (?) ability of the CBAM system is measured with a non-invasive, bone shock absorption (BSA) tool recently developed by our group. These Pb associated detrimental changes in bone and muscular parameters could collectively predispose to development of early osteoporosis associated susceptibility to fracture than those with no or lower Pb exposure. Furthermore, Pb affects osteoclastic and osteoblastic processes, hormonal signaling pathways, and the rate of growth plate chondrocyte maturation and contributes to functional postural instability (FPS) as an added risk for fall related fractures and injuries. These studies form the basis for our long-term core hypothesis: """"""""early life exposure to Pb detrimentally affects bone health as characterized by bone mass, macrostructure of the skeleton, and CBAM's structural integrity ability to sustain dynamic load, as well as postural stability/balance thereby predisposing the subjects to increased fracture risk later in life"""""""". The proposed study will be carried out with our existing Cincinnati Lead Study (CLS) cohort;thus allowing us to leverage the extensive data resources of our CLS prospective study which has experienced moderate to high levels of Pb exposure during their early life (late1970s and 1980's) and is now approaching bone maturation age (28-32 years).The first step towards addressing the long term core hypothesis is to evaluate the abilities of the proposed measures of bone's macrostructure, BMD, FPS and ?, collectively and individually for identifying Pb exposed subjects who meet or approach the independent thresholds from the literature for falls, and osteoporosis associated fracture and no fracture as well as from healthy subjects within the CLS age range.
This research is highly relevant to public health because results will yield, for the first time, new information about the impact of early life lead (Pb) exposure on combined bone and musculature health later in life among urban African American women in the US, many of whom experienced high levels of exposure to Pb during their formative years. This study will leverage the extensive data resources of our existing Cincinnati Lead Study prospective cohort which has experienced moderate to high levels of Pb exposure during their early life (late1970s and 1980's) and is now approaching bone maturation age (28-32 years). This first of its kind study will utilize objective and innovative methods to investigat the effect of early life exposure to Pb as a risk for developing decreased resistance to fracture and increased susceptibility to fall related fracture later in life.
