Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens

Abstract

Summary Rationale: Calcidiol can be employed to correct vitamin D deficiency. Main results: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. Significance: Calcidiol supplementation is effective and safe. Introduction The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D 3 ) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D 3 ) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested. Methods A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 μg/day, 40 μg/day, and 125 μg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety. Results In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound. Conclusions The results of this study demonstrate the shortand mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?

“…Over a three month period of supplementation, 25(OH)D levels were successfully raised without altering other markers related to bone and mineral metabolism. This also suggests that a safe and effective short- and mid-term effect on mineral metabolism occurs with both daily and weekly dosages of calcifediol when used to treat vitamin D inadequacy or deficiency in this population of subjects [61]. Thus, a potential additional advantage of calcifediol is that the increase in 25(OH)D is linear and independent of the baseline values of 25(OH)D [62].…”

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

“…Calcifediol has been reported to restore normal circulating levels of vitamin D more rapidly than cholecalciferol [ 98 , 99 , 100 ]. Reliable comparative evaluations of hydroxylated vitamin D metabolites vs. vitamin D-equivalent doses are lacking [ 101 ].…”

Cholecalciferol or Calcifediol in the Management of Vitamin D Deficiency

“…In this regard, we have found the first study published in 1977 in the journal Lancet by the Stamp et al British group, in which among patients with vitamin D deficiency, a difference in biological potency in the range between 6 and 12 was observed [ 62 ]. Subsequently, a US study was published on healthy young adults around 28 years old among whom a somewhat lower biological potency differential was observed, in the range between 3.5 and 8 [ 63 ]; the work of Cashman et al in adults over 50 years old, with a difference in biological potency of 4.2–4.99 [ 64 ]; the Swiss studies of Bischoff-Ferrari HA et al in post-menopausal women with a relative potency difference: 3,4 [ 65 ]; Jetter A et al in women aged 50 to 70 years with a relative power difference in the range between 2.23 and 5.59 [ 66 ]; the Italian work of Rossini M et al on post-menopausal women with vitamin D deficiency, with a very low relative potency difference of 1.66 [ 67 ]; and more recently, two clinical trials published in 2017 of young American adults around 35 years old, with a relative potency difference of 5.54 [ 68 ]; and in a study of Italian Caucasian post-menopausal women over 55 years old, with a potency difference ranging from 2.8 to 8 [ 69 ]. Finally, published in 2018, the comparative clinical trial of overweight or obese Dutch adults over 65 years old, with a relative potency difference estimated between 1.04 and 2.97 [ 70 ].…”