A Positive Dose–Response Effect of Vitamin D Supplementation on Site-Specific Bone Mineral Augmentation in Adolescent Girls: A Double-Blinded Randomized Placebo-Controlled 1-Year Intervention

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Abstract
The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo-controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae in a dose-responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers. Introduction: Adequate vitamin D intake protects the elderly against osteoporosis, but there exists no indisputable evidence that vitamin D supplementation would benefit bone mineral augmentation. The aim of this 1-year study was to determine in a randomized double-blinded trial the effect of 5 and 10 μg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake. Materials and Methods: Altogether, 228 girls (mean age, 11.4 ± 0.4 years) participated. Their BMC was measured by DXA from the femur and lumbar spine. Serum 25-hydroxyvitamin D [S-25(OH)D], intact PTH (S-iPTH), osteocalcin (S-OC), and urinary pyridinoline (U-Pyr) and deoxypyridinoline (U-Dpyr) were measured. Statistical analysis was performed both with the intention-to-treat (IT) and compliance-based (CB) method. Results: In the CB analysis, vitamin D supplementation increased femoral BMC augmentation by 14.3% with 5 μg and by 17.2% with 10 μg compared with the placebo group (ANCOVA, p = 0.012). A dose–response effect was observed in the vertebrae (ANCOVA, p = 0.039), although only with the highest dose. The mean concentration of S-25(OH)D increased (p < 0.001) in the 5-μg group by 5.7 ± 15.7 nM and in the 10-μg group by 12.4 ± 13.7 nM, whereas it decreased by 6.7 ± 11.3 nM in the placebo group. Supplementation had no effect on S-iPTH or S-OC, but it decreased U-DPyr (p = 0.042). Conclusions: Bone mineral augmentation in the femur was 14.3% and 17.2% higher in the groups receiving 5 and 10 μg of vitamin D, respectively, compared with the placebo group, but only 10 μg increased lumbar spine BMC augmentation significantly. Vitamin D supplementation decreased the concentration of bone resorption markers, but had no impact on bone formation markers, thus explaining increased bone mineral augmentation. However, the positive effects were noted with the CB method but not with IT.