Significance of Serum 24,25-Dihydroxyvitamin D in the Assessment of Vitamin D Status: A Double-edged Sword?

Abstract

BACKGROUND: 24,25(OH) 2 D] in serum may be both a nuisance and nutritionally valuable.

Assessment of vitamin D status – a changing landscape

“…Such a derivatization can overcome the main problems related to the measurement of vitamin D metabolites: a very low analyte concentration, thermal instability and low polarity of the target compounds. The most common Cooksontype reagent is PTAD [171,[175][176][177][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193][194], but other similar reactants such as MBOTAD [187], DMEQ-TAD [188] or DAPTAD [168,188,190] have also been tested. Today, the commercial Amplifex Diene from ABSciex is increasingly used [191,192] since it provides better sensitivity compared to PTAD.…”

LC-MS/MS for Identifying Patients with CYP24A1 Mutations

“…Inactivating mutations of CYP24A1 (cytochrome P450, family 24, subfamily A, polypeptide 1) cause hypercalcemia, hypercalciuria, and increased 1,25(OH) 2 D concentrations (12)(13)(14)(15)(16)(17)(18)(19)(20). In studies describing LC-MS/MS assays for 24,25(OH) 2 D quantification, the relationship between 25(OH)D and 24,25(OH) 2 D has been used as a nutritional marker for assessment of optimum vitamin D supplementation (21 ). Mutations that cause reduced or complete loss of 24-hydroxylase function result in low or undetectable serum 24,25(OH) 2 D or increased 25(OH)D/24,25(OH) 2 D ratio.…”

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency

“…Vitamin D synthesized in the skin [vitamin D3 (cholecalciferol)] or orally ingested [either vitamin D3 or vitamin D2 (ergocalciferol)] is metabolized in the liver by the enzyme 25-hydroxylase (CYP2R1) to form 25- [2][3][4]. Mutations in the CYP24A1 gene are associated with partial or total loss of 24-hydroxylase activity, which in turn leads to hypercalcaemic conditions [5][6][7]. The production of 24,25(OH) 2 D3 has been shown to be 25(OH)D3-dependent, and is moderately affected by vitamin D supplementation [5,6]; the physiological role of this metabolite remains to be established, although it is known to be involved in embryogenesis, cartilage development and fracture repair [8][9][10].…”

“…Furthermore, the relationship between circulating 25(OH)D3 concentrations and clinical outcomes such as osteoporosis and fracture risk may differ between racial groups, raising the question of whether 25(OH)D3 provides a reliable estimate of vitamin D status in all populations [18,19]. For these reasons, increasing attention is being paid to the measurement of 24,25(OH) 2 D3 (the major circulating catabolite of vitamin D), and the ratio of 24,25(OH) 2 D3 to 25(OH)D3, as potential markers of vitamin D catabolism and predictors of the serum 25(OH)D response to vitamin D supplementation [5,6,12,18,20].…”