Osteopathy and resistance to vitamin D toxicity in mice null for vitamin D binding protein

Cellular uptake of steroid carrier proteins—Mechanisms and implications

“…Surprisingly, some phenotypes observed in this model such as protection from vitamin D toxification are incompatible with the free hormone hypothesis (Safadi et al, 1999). Similarly, phenotypic characterization of mice lacking CBG revealed some surprising findings.…”

“…In these animals, lack of the carrier results in an inability to properly deliver 25-OH vitamin D 3 to the kidney for uptake and activation. Instead, most of the metabolite is wrongfully directed to the liver and catabolized, or lost in the kidney through urinary excretion (Safadi et al, 1999). A crucial role for the carrier in renal targeting and activation of 25-OH vitamin D 3 was also supported by the observation that DBP knockout mice are protected rather than sensitized to vitamin D toxification (Safadi et al, 1999).…”

Vitamin D metabolites in captivity? Should we measure free or total 25(OH)D to assess vitamin D status?

“…This fundamental concept has been well established for other hormones, such as sex steroid and thyroid hormones (1- However, DBP-null mice maintain normal calcium homeostasis when fed a vitamin D-replete diet and have no evidence of bone disease despite having extraordinarily low levels of total circulating 25(OH)D and 1,25(OH)2D, approximately 1% of wild type controls (8,10). In addition, in DBP-null mice, vitamin D is more rapidly taken up by the liver, and 1,25(OH)2D had a more rapid effect on calbindin induction in the intestines.…”

Vitamin D-binding protein: one more piece in the puzzle of acromegalic osteopathy?

“…More than 80 % of circulating vitamin D (i.e., both 25(OH)-vitamin D and 1,25-dihydroxy-vitamin D3) is bound to vitamin D-binding protein (VDBP) which acts as regulator of hormone bio-availability to target tissue [12]. Indeed, VDBP could be either a reservoir of vitamin D prolonging its half-life or a modulator of hormone biological activity [9,10,13]. In clinical conditions, the inhibitory effects of VDBP on vitamin D activity seem to be predominant and some individuals may be misclassified as vitamin D sufficient or insufficient by measurement of serum 25(OH)vitamin D alone in the presence of modifications in VDBP production.…”