Abstract
This study was performed to investigate the effect of monthly oral administration of 500 μg of calcidiol (25-hydroxyvitamin D3) for 4 months on both serum vitamin D levels and sequential changes of parameters of calcium metabolism; 18 normal women aged 24–72 years were investigated. There was a significant increase of serum 25(OH)D after the first administration; thereafter all values persisted significantly higher compared to the basal value (P < 0.001). Mean 1,25(OH)2D serum levels peaked at day 3 and then tended to stabilize following day 30. During the first month, all mean values observed following the initial administration were significantly higher than basal values. The first calcidiol dose produced a significant reduction of serum PTH levels (P < 0.001), which then remained constant over time. Concerning serum calcium and phosphorus, we were not able to demonstrate any significant change during the entire observation period. Considering the single values for both serum ionized and total calcium, the values of Ca2+ exceeded upper limits of normal on only two occasions. Regarding biochemical markers of bone remodeling, mean changes of serum bone isoenzyme of alkaline phosphatase activity showed a significant trend to decrease, starting at day 30. No significant changes of serum CTX values were noted. Overall, 24-h urinary excretion of calcium did not change, seven values exceeding the threshold of 4 mg/kg body weight. Monthly administration of 500 μg of 25-hydroxyvitamin D3 may be considered an alternative for vitamin D repletion, without any detrimental effect.
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Van der Wielen RP, Löwik MR, Van den Berg H, de Groot LC, Haller J, Moreiras O, Van Staveren WA (1995) Serum vitamin D concentrations among elderly people in Europe. Lancet 346:207–210
Orwoll E, Nielson CM, Marshall LM, Lambert L, Holton KF, Hoffman AR, Barrett-Connor E, Shikany JM, Dam T, Cauley JAJ (2009) Vitamin D deficiency in older men. J Clin Endocrinol Metab 94:1214–1222
Romagnoli E, Caravella P, Scarnecchia L, Martinez P, Minisola S (1999) Hypovitaminosis D in an Italian population of healthy subjects and hospitalized patients. Br J Nutr 81:133–137
Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281
Chapuy MC, Meunier PJ (1995) Prevention and treatment of osteoporosis. Aging Clin Exp Res 7:164–173
Pepe J, Romagnoli E, Nofroni I, Pacitti MT, De Geronimo S, Letizia C, Tonnarini G, Scarpiello A, D’Erasmo E, Minisola S (2005) Vitamin D status as the major factor determining the circulating levels of parathyroid hormone: a study in normal subjects. Osteoporos Int 16:805–812
Chapuy MC, Arlot ME, Delmas PD, Meunier PJ (1994) Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. Br Med J 308:1081–1082
Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Br Med J 326:469–474
Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbel FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludiam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683
Petta S, Cammà C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, Licata G, Porcasi R, Marchesini G, Craxì A (2010) Low vitamin D serum levels is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology 51:1158–1167
Michaud J, Naud J, Ouimet D, Demers C, Petit J-L, Leblond FA, Bonnardeaux A, Gascon-Barré M, Pichette V (2010) Reduced hepatic synthesis of calcidiol in uremia. J Am Soc Nephrol 21:1488–1497
Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF (1998) Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int 8:222–230
Romagnoli E, Mascia ML, Cipriani C, Fassino V, D’Erasmo E, Mazzei F, D’Erasmo E, Carnevale V, Scillitani A, Minisola S (2008) Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (D3) in the elderly. J Clin Endocrinol Metab 93:3015–3020
Carnevale V, Dionisi S, Nofroni I, Romagnoli E, Paglia F, De Geronimo S, Pepe J, Clemente G, Tonnarini G, Minisola S (2004) Potential clinical utility of a new IRMA for parathyroid hormone in postmenopausal patients with primary hyperparathyroidism. Clin Chem 50:626–631
R Development Core Team (2011) R: a language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria
Peacock M, Liu G, Carey M, McClintock R, Ambrosius W, Hui S, Johnston CC (2000) Effect of calcium on 25(OH) vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J Clin Endocrinol Metab 85:3011–3019
Haddad JG Jr, Rojanasathit S (1976) Acute administration of 25-hydroxycholecalciferol in man. J Clin Endocrinol Metab 42:284–290
Heaney RP, Horst RL, Cullen DM, Armas AG (2009) Vitamin D3 distribution and status in the body. J Am Coll Nutr 28:252–256
Cipriani C, Romagnoli E, Scillitani A, Chiodini I, Clerico R, Carnevale V, Mascia ML, Battista C, Viti R, Pileri M, Eller-Vainicher C, Minisola S (2010) Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency: a prospective intervention study. J Clin Endocrinol Metab 95:4771–4777
Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women. A randomized controlled trial. JAMA 303:1815–1822
Vieth R, Fuleihan El Hajj (2005) There is no threshold level for parathyroid hormone as 25-hydroxyvitamin D concentrations increase. J Endocrinol Invest 28:183–186
Heaney RP (2005) Serum 25-hydroxyvitamin D and parathyroid hormone exhibit thresholds behavior. J Endocrinol Invest 28:180–182
Qaw F, Calverley MJ, Schroeder NJ, Trafford DJ, Makin HL, Jones J (1993) In vivo metabolism of the vitamin D analog, dihydrotachysterol: evidence for formation of 1α,25- and 1β,25-dihydroxy-dihydrotachysterol metabolites and studies of their biological activity. J Biol Chem 268:282–292
Kawahara M, Iwasaki Y, Sakaguchi K, Taguchi T, Nishiyama M, Nigawara T, Tsugita M, Kambayashi M, Suda T, Hashimoto K (2008) Predominant role of 25(OH)D in the negative regulation of PTH expression: clinical relevance for hypovitaminosis D. Life Sci 26:677–683
Ballanti P, Minisola S, Pacitti MT, Scarnecchia L, Rosso R, Mazzuoli GF, Bonucci E (1997) Tartrate-resistant acid phosphatase activity as osteoclastic marker: sensitivity of cytochemical assessment and serum assay in comparison with standardized osteoclast histomorphometry. Osteoporos Int 7:39–46
Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IA (2005) Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab 90:2122–2126
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This study was partly funded by Bruno Farmaceutici, Rome, Italy.
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S. Minisola has served as speaker for Abiogen, Amgen, Bruno Farmaceutici, Eli Lilly, Merck Sharp & Dohme, Nycomed, Neopharmed, Roche, and Warner Chilcott. He also served in advisory boards of Amgen, Eli Lilly, Glaxo SmithKline, Medtronic, Merck Sharp & Dohme, Novartis, and Pfizer. All other authors have stated that they have no conflict of interest.
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Russo, S., Carlucci, L., Cipriani, C. et al. Metabolic Changes Following 500 μg Monthly Administration of Calcidiol: A Study in Normal Females. Calcif Tissue Int 89, 252–257 (2011). https://doi.org/10.1007/s00223-011-9513-1
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DOI: https://doi.org/10.1007/s00223-011-9513-1