Short-term effects on bone turnover markers of a single high dose of oral vitamin D₃.
BACKGROUND
Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported.


OBJECTIVE
The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D₃.


METHODS
Twelve elderly subjects (eight women, four men; mean age 76 ± 3 yr) were given a single oral bolus of 600,000 IU vitamin D₃. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D₃ administration. Twenty-four subjects served as controls.


METHODS
Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase.


RESULTS
No relevant changes in 25OHD and bone turnover markers were observed in the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 ± 17.1 ng/ml (P < 0.001) at d 3. Subsequently it slowly decreased to 35.2 ± 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 ± 5.6 ng/ml). Mean serum PTH concentration decreased by 25-50% and serum 1,25-dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60. No changes were observed in serum bone-specific alkaline phosphatase.


CONCLUSIONS
Our results indicate that the use of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or prevent vitamin D deficiency.
Rheumatology Unit, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134 Verona, Italy. maurizio.rossini@univr.it
Maurizio
M
Rossini
Davide
D
Gatti
Ombretta
O
Viapiana
Elena
E
Fracassi
Luca
L
Idolazzi
Silvia
S
Zanoni
Silvano
S
Adami
D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001711:Biotransformation; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D010748:Phosphopeptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000150:complications / Q000188:drug therapy*
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; C062121:N-propeptide type I collagen; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010455:Peptides; D010748:Phosphopeptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D002762:Cholecalciferol; D002117:Calcitriol; D002112:Calcifediol