title: 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.
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.
  
  
  BACKGROUND
  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 microg vitamin D3 supplementation on bone mineral augmentation in adolescent girls with adequate dietary calcium intake.
  
  
  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 microg and by 17.2% with 10 microg 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-microg group by 5.7 +/- 15.7 nM and in the 10-microg 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 microg of vitamin D, respectively, compared with the placebo group, but only 10 mug 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.
authors.affiliation: Calcium Research Unit, Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki, Finland.
authors.forename: Heli T
authors.initials: HT
authors.lastname: Viljakainen
authors.forename: Anna-Mari
authors.initials: AM
authors.lastname: Natri
authors.forename: Merja
authors.initials: M
authors.lastname: Kärkkäinen
authors.forename: Minna M
authors.initials: MM
authors.lastname: Huttunen
authors.forename: Anette
authors.initials: A
authors.lastname: Palssa
authors.forename: Jette
authors.initials: J
authors.lastname: Jakobsen
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Cashman
authors.forename: Christian
authors.initials: C
authors.lastname: Mølgaard
authors.forename: Christel
authors.initials: C
authors.lastname: Lamberg-Allardt
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D002112:Calcifediol / Q000097:blood*; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000652:urine; D002648:Child; D002762:Cholecalciferol / Q000494:pharmacology*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D005387:Finland; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010710:Phosphates / Q000652:urine; D011859:Radiography
chemical_list: D015415:Biomarkers; D010710:Phosphates; D002762:Cholecalciferol; D002112:Calcifediol; D002118:Calcium