Bone status and bone dynamics in body size childhood: do longitudinal changes make a difference?
The burden of fragility fractures is highest in adulthood. However, the approach currently used to explain the etiology of suboptimal bone strength is built on the premise that there is important tracking of this characteristic throughout the life course. In this way, the probability of fracture in old age may be partly traced back to the maximum bone strength attained during the first decades of life. In this context,context, modifiable factors that modulate the accrual of bone mass may be important intervention targets. Anthropometric determinants of bone health assume a great importance, in view of the changing trends of childhood overweight in many populations. Presently, there is no clear understanding of the importance of early changes in body size from birth up to the time of measurement as possible determinants of bone quality. In particular, it is not clear if, in the prediction of bone properties, longitudinal changes in body size add relevant information in addition to anthropometry measured cross-sectionally. Therefore, by using prospective data from a subsample of a large birth cohort re-evaluated at 4 years of age and at 8 years of age, our main objectives are: a) To quantify, at 8 years old, the cross-sectional associations between body size and composition and different dimensions of bone quality: mechanical, maturational and biochemical; b) To assess whether longitudinal changes in body size since birth improve the prediction of bone properties at 8 years of age in addition to body size and composition at the same age. To accomplish these objectives, we will use a subsample of the Generation XXI cohort, which is a prospective population-based birth cohort established in a defined geographic area in Porto, Portugal. Pregnant women were recruited in five level III maternity units between April 2005 and August 2006. A total of 8647 children and their mothers were enrolled at baseline. At 4 years of age, 86% of these children were re-evaluated. We will use a large amount of previously collected information on anthropometric variables at birth (birth weight and ponderal index) and at 4 years of age (weight, body mass index and ponderal index). For the purpose of the present project, we will collect additional information at 8 years of age for 400 children (nested in the reevaluation of the cohort), comprising 200 boys and 200 girls. Besides anthropometry, this project will specifically include data on three different dimensions of bone status and dynamics. Physical properties of bone will be estimated using the following parameters obtained by whole-body dual-energy X-ray absorptiometry (DXA) scans: bone mineral density, bone mineral content and bone area. Bone maturity will be estimated through skeletal age, measured using DXA images of the non-dominant wrist and hand and classified according to the Greulich and Pyle method. Rate of bone turnover will be assessed using serum procollagen type I N propeptide (PINP) and serum C-terminal telopeptide of type I collagen (CTX), respectively, as markers of formation and resorption. Using these data we will take the following analytical approaches: 1. Quantify the cross-sectional associations between body size (height, weight, and BMI) and composition (fat mass and fat-free mass) at 8 years of age and 1.1. Bone physical properties at 8 years (bone mineral density, bone mineral content and bone area) 1.2. Skeletal age at 8 years 1.3. Serum concentrations of collagenous bone formation and resorption markers at 8 years (PINP and CTX) 2. Use path analysis to simultaneously assess the relative magnitude of the associations between bone parameters at 8 years old and 2.1 body size at birth 2.2. body size at 4 years old 2.3. body size at 8 years old 3. Compare bone properties at 8 years of age between the following groups, specifically aiming at assessing if weight loss may have a detectable effect on bone quality: 3.1. children whose weight remained in the normal weight range throughout follow-up 3.2. children who were in the upper quantiles of the distribution at birth or 4 years of age but whose BMI decreased to healthy values at 8 years of age. Knowing the impact of different longitudinal changes, and particularly the result of weight loss early in life, will be relevant forin clarifying the role impact of interventions to reduce obesity on the development of bone strength. In a methodological perspective, we will be able to clarify the benefit of a longitudinal in relation to a cross-sectional approach with regard to the etiology development of bone quality strength throughout the life course.