Early childhood as a sensitive period for the effect of growth on childhood bone mass: Evidence from Generation XXI birth cohort

Background To identify sensitive periods for the effect of early life growth on childhood bone mass we compared the associations between weight and length/height velocities from birth to age six and bone mineral content (BMC) and areal density (aBMD) at 7 years of age. Methods: We analyzed data from 1853 participants from the Generation XXI birth cohort scanned with a whole body dual-energy X-ray absorptiometry system. Velocities of growth in weight and length/height were obtained through linear spline multilevel models on the basis of data collected during routine health examinations. Using linear regression we computed associations of birth weight, birth length, five weight velocities ("early neonatal": 0-10 days, "early infancy": 10 days-3 months, "late infancy": 3-12 months, "early childhood": 1-3 years, and "later childhood": 3-6 years) and four length/height velocities ("early infancy": 0-3 months, "late infancy": 3-12 months, "early childhood": 1-3 years, and "later childhood": 3-6 years) with outcomes BMC, aBMD, height and height-adjusted BMC at age seven. Confounding by maternal and child characteristics was addressed and effects of growth velocities were adjusted to preceding growth. Results: Weight and length/height velocities up to the age of six were associated with increased bone mass, areal density and height at 7 years with the strongest associations observed for growth in early childhood. In this age period, after concurrent height and confounder adjustment, one standard deviation (SD) increase in weight velocity was associated with higher BMC z-scores: 0.27 (95%CI: 0.22, 0.32) in girls and 0.24 (95%CI: 0.19, 0.29) in boys. Height velocity was also associated with greater height -adjusted BMC z-score: 0.12 (95%CI: 0.07, 0.17) per SD in girls and 0.11 (95%CI: 0.06, 0.16) in boys. The pattern of associations was similar, albeit attenuated, after adjusting for preceding growth. Conclusion: Growth in second and third years of life may represent a sensitive period for the effect of growth on childhood bone mass, partly through their effect on concurrent body size.