Establishing the Precursors of Osteoporosis in Children

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DESCRIPTION (provided by applicant): Elucidating childhood precursors of osteoporosis may lead to interventions that prevent or mitigate osteoporosis later in life. The central focus of this application is to investigate bone mass as measured by DEXA, including bone mineral content (BMC), bone area (BA) and bone mineral density (BMD) in relation to a wide range of putative precursors of osteoporosis. We will study a large prospective twin cohort (-2,000 twin pairs) of children and adolescents, enrolled previously in 1998-2000 in Anqing, China, with an age range of 6-21 years. The twins are currently followed by a NIH funded study to identify precursors of metabolic syndrome (MS). The specific aims are: (1) To measure biomarkers that are known or suspected to affect bone health in 1,500 twin pairs at baseline and follow-up study, including bone modeling and remodeling markers: osteoprotegerin (OPG), soluble receptor activator of NFKB ligand (sRANKL), parathyroid hormone (PTH), osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRAP-5b); nutritional markers: magnesium, vitamin K1, and 25(OH) vitamin D; and also examine other relevant biomarkers covered by the funded MS study, including steroid hormones: androgen, estrogen, testosterons, LH, and FSH; metabolic markers: fasting and 2-hr post OGTT insulin, glucose, HOMA-IR, fasting lipids; growth hormones: insulin-like growth factor (IGF-I); adipocyte markers: leptin, adiponectin; and inflammatory markers: C-reactive protein (CRP), lnterleukin-6 (IL-6), and tumor necrosis factor (TNF); (2) To conduct cross-sectional and longitudinal co-twin analyses to test the following hypotheses: (a) BMC, BA and BMD attained levels are associated with biomarker levels at the baseline and follow-up survey, respectively; (b) BMC, BA, and BMD changes between the baseline and follow-up survey are associated with biomarker levels at the baseline survey; (c) BMC, BA, and BMD changes are associated with biomarker changes between the baseline and follow-up surveys. We will further examine if the above relationships are independent of other important covariates, including age, gender, pubertal stage, body weight and composition, nutritional intake, and physical activity, and if there are interactions between the biomarkers and the covariates. The identification of potential important precursors of osteoporosis in children and adolescents would represent a huge step forward in our understanding of the biological basis of bone mass and should have important implications for the detection of individuals at high risk for osteoporosis.