ORIGINAL RESEARCH Metabolic Changes Following 500 lg Monthly Administration of Calcidiol: A Study in Normal Females Stefania Russo • Luciano Carlucci • Cristiana Cipriani • Alessandro Ragno • Sara Piemonte • Romano Del Fiacco • Jessica Pepe • Valeria Fassino • Serena Arima • Elisabetta Romagnoli • Salvatore Minisola Received: 23 December 2010 / Accepted: 5 June 2011 / Published online: 24 June 2011 Ó Springer Science+Business Media, LLC 2011 Abstract This study was performed to investigate the effect of monthly oral administration of 500 lg of calcidiol (25-hydroxyvitamin D 3 ) for 4 months on both serum vita- min 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) 2 D 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 Ca 2? 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 sig- nificant 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 lg of 25-hydroxyvitamin D 3 may be considered an alternative for vitamin D repletion, without any detrimental effect. Keywords Calcidiol Á Calcitriol Á Parathyroid hormone Á Bone remodeling Vitamin D is a hormone essential for skeletal tissue and for different physiological systems or functions. A number of studies [1–3] have shown that a large proportion of people are vitamin D-insufficient or -deficient as documented by serum levels of 25(OH)D below 30 and 20 ng/ml, respec- tively [4]. Low 25(OH)D levels determine a compensatory increase in serum parathyroid hormone (PTH) levels that is detrimental for skeletal health [5, 6]. As a consequence, several intervention studies have been performed in order to demonstrate the efficacy of vitamin D supplementation at reducing the incidence of nonvertebral fracture [7, 8], even though not all the studies [9] have shown consistent results. However, there are some specific clinical condi- tions in which the administration of ergocalciferol or cholecalciferol might not represent the best therapeutic 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. S. Russo Á L. Carlucci Á C. Cipriani Á S. Piemonte Á R. D. Fiacco Á J. Pepe Á V. Fassino Á E. Romagnoli Á S. Minisola (&) Department of Internal Medicine and Medical Disciplines, ‘‘Sapienza,’’ University of Rome, Via del Policlinico 155, 00161 Rome, Italy e-mail: salvatore.minisola@fastwebnet.it A. Ragno Internal Medicine and Nephrology, ‘‘Regina Apostolorum’’ Hospital, Via san Francesco 50, Albano Laziale, 00041 Rome, Italy S. Arima Department of Methods and Models for Economy, Territory, and Finance, ‘‘Sapienza’’, University of Rome, Via del Castro Laurenziano 9, 00161 Rome, Italy 123 Calcif Tissue Int (2011) 89:252–257 DOI 10.1007/s00223-011-9513-1