Pharmacokinetic profile and effect on bone markers and muscle strength of two daily dosage regimens of calcifediol in osteopenic/osteoporotic postmenopausal women

Gonnelli, Stefano; Pitinca, Maria Dea Tomai; Camarri, Silvia; Lucani, Barbara; Franci, Beatrice; Nuti, Ranuccio; Caffarelli, Carla

doi:10.1007/s40520-020-01779-7

Cited by 12 publications

(10 citation statements)

References 35 publications

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“…Calcidiol at a dose of 30 µg/d for 6 months did not develop hypercalcaemia in postmenopausal women, nor did 20 µg/d of calcidiol (Gonnelli et al 2021). However, one participant who was treated with 30 µg/d of calcidiol was found to have a borderline hypercalciuria (24h U-Ca 8.0 mmol), but the study did not mention retesting for elevated calcium excretion.…”

Section: Vitamin D 30 To 357 µG/dmentioning

confidence: 84%

Preparatory work for the update of the tolerable upper intake levels for vitamin D

Lamberg‐Allardt

Adebayo

Peltonen

et al. 2023

EFSA Supporting Publications

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This technical report describes the collection of data and appraisal of scientific evidence in relation to the assessment of Tolerable Upper Intake Levels (UL) for vitamin D. Five systematic reviews (SR) were conducted following a tailored literature search, data extraction, evidence appraisal (i.e., risk of bias (RoB) assessment) and evidence synthesis. Narrative reviews were conducted to gather contextual evidence relevant to the interpretation of the main body of evidence (BoE). In the SR on bioavailability of calcidiol compared to native vitamin D3, 4304 records were identified and reduced to 12 individual records after screening for eligibility. The evidence appraisal revealed an overall low to high RoB of the individual studies. The available BoE demonstrated higher relative bioavailability of calcidiol compared to native vitamin D3 with a conversion factor of about 2 across baseline 25(OH)D concentrations of 30 to 55 nmol/L. In the SR on hypercalcaemia and hypercalciuria, 8277 records were identified and reduced to 37 individual records after screening for eligibility. The evidence appraisal revealed an overall low to high RoB of the individual studies. The available evidence demonstrated that occurrence of persistent hypercalcemia and hypercalciuria with high doses of vitamin D supplementation was rare. Nevertheless, increased risk of persistent hypercalciuria was observed with 250 μg/d of vitamin D supplementation. In the SRs on bone fractures, falls, bone mineral density (BMD), bone mineral content, and bone strength, 15 541 records were identified and reduced to 20 individual records after screening for eligibility. The evidence appraisal revealed an overall low to moderate RoB of the individual studies. No clear signs of adverse effects of high vitamin D intake were found in relation to bone fractures, falls, or areal BMD, but volumetric BMD was reduced with 100 and 250 μg/d of vitamin D.

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Section: Vitamin D 30 To 357 µG/dmentioning

confidence: 84%

Preparatory work for the update of the tolerable upper intake levels for vitamin D

Lamberg‐Allardt

Adebayo

Peltonen

et al. 2023

EFSA Supporting Publications

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“…• it was reported that retesting for elevated Ca concentration/ excretion was performed, i.e., the result was confirmed by retesting within a given timeand vitamin D form investigated was calcidiol in five studies (Cashman et al, 2012;Minisola et al, 2017;Vaes et al, 2018b;Graeff-Armas et al, 2020;Gonnelli et al, 2021) and either vitamin D 2 or D 3 in the remaining studies. Doses of calcidiol ranged from 5 to 40 μg/day (Minisola et al, 2017).…”

Section: Persistent Hypercalcaemia and Hypercalciuriamentioning

confidence: 90%

Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate

Turck¹,

Bohn²,

Castenmiller³

et al. 2023

EFS2

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Following two requests from the European Commission (EC), the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin D and to propose a conversion factor (CF) for calcidiol monohydrate into vitamin D 3 for labelling purposes. Vitamin D refers to ergocalciferol (vitamin D 2 ), cholecalciferol (vitamin D 3 ), and calcidiol monohydrate. Systematic reviews of the literature were conducted to assess the relative bioavailability of calcidiol monohydrate versus vitamin D 3 on serum 25(OH)D concentrations, and for priority adverse health effects of excess vitamin D intake, namely persistent hypercalcaemia/hypercalciuria and endpoints related to musculoskeletal health (i.e. falls, bone fractures, bone mass/density and indices thereof). Based on the available evidence, the Panel proposes a CF for calcidiol monohydrates of 2.5 for labelling purposes. Persistent hypercalciuria, which may be an earlier sign of excess vitamin D than persistent hypercalcaemia, is selected as the critical endpoint on which to base the UL for vitamin D. A lowest-observed-adverse-effect-level (LOAEL) of 250 μg/day is identified from two randomised controlled trials in humans, to which an uncertainty factor of 2.5 is applied to account for the absence of a no-observed-adverse-effect-level (NOAEL). A UL of 100 μg vitamin D equivalents (VDE)/day is established for adults (including pregnant and lactating women) and for adolescents aged 11-17 years, as there is no reason to believe that adolescents in the phase of rapid bone formation and growth have a lower tolerance for vitamin D compared to adults. For children aged 1-10 years, a UL of 50 μg VDE/day is established by considering their smaller body size. Based on available intake data, European populations are unlikely to exceed the UL, except for regular users of food supplements containing high doses of vitamin D.

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“…In a monocentric open-label randomized trial comparing weekly calcifediol (dosage reported as 7000 IU/week) with vitamin D 3 (at dosages of 7000 IU/week, 100,000 IU every 2 months or 300,000 IU as a single dose) in 107 post-menopausal women, calcifediol achieved target serum 25(OH)D concentrations more rapidly than vitamin D 3 and, at 6 months, was associated with significantly (p < 0.05) greater improvement than vitamin D 3 in lower extremity muscle strength/function assessed using the 30-s Sit-to-Stand test and Timed-Up-and-Go test [71]. At 6 months, the group treated with calcifediol 30 µg/day showed a modest but statistically significant increase in upper limb (handgrip) strength [90]. In an nonblinded, nonrandomized, uncontrolled, prospective cohort study, calcifediol 20 µg/day was administered to 113 post-menopausal women with osteoporosis and/or serum 25(OH) D concentrations < 75 nmol/L.…”

Section: Physical Performance and Muscle Strength Parameters In Post-...mentioning

confidence: 92%

“…In recent years, however, several studies conducted with calcifediol have reported non-laboratory clinical end points. The design features and outcomes of these studies are summarized in Table 3 [60,70,71,85,[89][90][91][92][93][94][95][96][97][98][99][100].…”

Section: Studies Of Supplemental Calcifediol In Diseasementioning

confidence: 99%

“…Several studies have examined the effects of calcifediol supplementation on physical performance and muscle strength parameters in post-menopausal women or frail and elderly patients with vitamin D insufficiency [60,70,71,[89][90][91]. Two small comparative RCTs of calcifediol and vitamin D 3 reported modest benefits with calcifediol [60] or no change from baseline with either supplement [89].…”

Section: Physical Performance and Muscle Strength Parameters In Post-...mentioning

confidence: 99%

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Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency

2023

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Background In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D 3 ) has recently become available more widely. Methods By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D 3 , and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions. Results For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3−10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D 3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D 3 , calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D 3 , it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D 3 and thus is less prone to sequestration in adipose tissue. Conclusion Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D 3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.

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Pharmacokinetic profile and effect on bone markers and muscle strength of two daily dosage regimens of calcifediol in osteopenic/osteoporotic postmenopausal women

Cited by 12 publications

References 35 publications

Preparatory work for the update of the tolerable upper intake levels for vitamin D

Preparatory work for the update of the tolerable upper intake levels for vitamin D

Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate

Calcifediol: a review of its pharmacological characteristics and clinical use in correcting vitamin D deficiency

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