The aim of this meta-analysis was to compare the antifall efficacy of native vitamin D to that of its hydroxylated analogs alfacalcidol and calcitriol. Randomized clinical trials comparing oral native vitamin D and its analogs alfacalcidol and calcitriol to a placebo were included. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, a hand search of abstracts, as well as reference lists. The time range was January 1995 to May 2007. Data were abstracted and scored by two investigators. The core analysis was based on double-blind trials, while open trials were included as a robustness analysis. Relative risks (RRs) for falls while allocated to D-hormone analogs or vitamin D were calculated. Publication bias and robustness were formally tested. Fourteen trials including 21,268 subjects were included. Using double-blind data only, vitamin D-hormone analogs provided a statistically significant lower level of risk for falling compared to native vitamin D: RR = 0.79 (95% confidence interval 0.64-0.96) vs. 0.94 (0.87-1.01) (intergroup difference P = 0.049). The dropout rates observed in the two sets of trials were comparable: 0.33% per month. Publication bias investigation did not report any significant trend for selective publication favoring active treatment arms. Upon current evidence, D-hormone analogs seem to prevent falls to a greater extent than their native compound. Long-term, prospective, head-to-head, confirmatory trials are required to address the exact role of vitamin D and D-hormone analogs in the prevention of falls and fractures.
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http://dx.doi.org/10.1007/s00223-008-9102-0 | DOI Listing |
Endocrinology
September 2024
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
CYP24A1 is a multifunctional, P450 mitochondrial enzyme that catabolizes the vitamin D hormone (calcitriol, 1,25(OH)2D3), its precursor (calcifediol, 25(OH)D3), and numerous vitamin D metabolites. In the kidney, Cyp24a1 is induced by 1,25(OH)2D3 and fibroblast growth factor 23 (FGF23) and potently suppressed by PTH to control the circulating levels of 1,25(OH)2D3. Cyp24a1 is controlled by a pair of promoter proximal (PRO) vitamin D response elements (VDREs) that are aided by distal, downstream (DS) enhancers.
View Article and Find Full Text PDFInt J Mol Sci
November 2021
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-established techniques of chromatin immunoprecipitation coupled to next-generation DNA sequencing that have now been linked directly to CRISPR-Cas9 genomic editing in culture cells and in mouse tissues in vivo. Accordingly, these techniques have established that the vitamin D hormone modulates sets of cell-type specific genes via an initial action that involves rapid binding of the VDR-ligand complex to multiple enhancer elements at open chromatin sites that drive the expression of individual genes.
View Article and Find Full Text PDFJ Neuroendocrinol
January 2020
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
The active vitamin D hormone, 1,25-dihydroxyvitamin D , exerts many physiological actions in the body, including effects on the nervous system. Studies of steroidogenesis in cells of the nervous system and elsewhere not only indicate that 1,25-dihydroxyvitamin D affects steroidogenic pathways but also suggest varying responses in different cell types. For example, 1,25-dihydroxyvitamin D stimulates the expression of aromatase in human glioma but not in human neuroblastoma cells or rat astrocytes.
View Article and Find Full Text PDFNeuropharmacology
March 2019
Emory University School of Medicine, Department of Emergency Medicine, 1365 B Clifton Rd NE, Suite 5100, Atlanta, GA, 30322, USA. Electronic address:
The field of neuroprotection after brain injuries has been littered with failed clinical trials. Finding a safe and effective treatment for acute traumatic brain injury remains a serious unmet medical need. Repurposing drugs that have been in use for other disorders is receiving increasing attention as a strategy to move candidate drugs more quickly to trial while reducing the very high cost of new drug development.
View Article and Find Full Text PDFNeuroscience
October 2016
Queensland Brain Institute, University of Queensland, Qld 4072, Australia; Queensland Centre for Mental Health Research, Wacol, Qld 4076, Australia. Electronic address:
Vitamin D regulates multiple factors including those involved in the ontogeny of dopaminergic systems. It has been shown that in neonatal rats maternally deprived of vitamin D, dopamine (DA) turnover is decreased with associated reductions in one catabolic enzyme, catechol-o-methyl transferase (COMT). To directly examine this signaling relationship, in the present study we have over-expressed the vitamin D receptor (VDR) in neuroblastoma SH-SY5Y cells in order to examine the mechanisms by which the active vitamin D hormone, 1,25(OH)2D3, via its receptor VDR, affects DA production and turnover.
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