Bone metabolism markers predict increase in bone mass, height and sitting height during puberty depending on the VDR Fok1 genotype

OBJECTIVES: Longitudinal growth and bone mass accumulation are two important phenomena during puberty, resulting in attainment of peak bone mass (PBM) and final height. They are thought to be under strong genetic control, with the vitamin D receptor (VDR) gene being among the candidate genes. Bone metabolism markers are reported to be good predictors of longitudinal growth and bone mass increase. The purpose of this longitudinal study was to evaluate whether bone metabolism markers predict bone mass and height increase differently according to Fok1 VDR genotype throughout puberty in healthy adolescents. PATIENTS AND MEASUREMENTS: At the start of the study 130 girls were aged 10.8 (range 8.5-12.8) years and 125 boys were aged 11.8 (range 9.4-14.6) years at the first visit. Markers of bone formation and bone resorption were measured at the first visit, as well as height and sitting height (SH), and bone mineral content (BMC) of the lumbar spine, femur, arm and total body. All measurements were repeated after 2 years. RESULTS: A higher BMC of the femur, distal arm and total body was found in ff boys at the first visit, which was not related to higher levels of bone metabolism markers in this group. In girls, no differences between genotypes were seen in BMC (increase). However, concentrations of markers of bone formation [alkaline phosphatase (AP), bone-specific alkaline phosphatase (BAP), procollagen aminoterminal propeptide (PINP)] and bone resorption [type I carboxyterminal telopeptide (ICTP)] were higher in ff girls. Regression coefficients between bone metabolism markers and bone mass increase differed according to genotype and sex. A similar pattern was found for height and SH (increase), the latter as a representative of growth of the axial skeleton, mainly consisting of cancellous bone. CONCLUSIONS: Our data suggest that the predicting capacities of bone metabolism markers on bone mass (increase), height and SH (increase) are genotype dependent. Their use as predictors of final height or PBM therefore remains questionable without knowing the genotype