Horm Metab Res 2020; 52(03): 168-178
DOI: 10.1055/a-1114-6072
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Intravenous 25OHD Supplementation on Bone Turnover and Inflammation in Prolonged Critically Ill Patients

1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
,
Ilse Vanhorebeek
1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
,
Sophie Van Cromphaut
1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
,
Pieter J. Wouters
1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
,
Inge Derese
1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
,
Alexander Dehouwer
1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
,
Holger Jon Møller
2  Department of Clinical Medicine and Clinical Biochemistry, Aarhus University, Aarhus, Denmark
,
Troels K. Hansen
3  Department of Clinical Medicine - Steno Diabetes Center Aarhus, Aarhus University, Aarhus, Denmark
,
Jaak Billen
4  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, KU Leuven, Belgium
,
Chantal Mathieu
4  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, KU Leuven, Belgium
,
Roger Bouillon
4  Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, KU Leuven, Belgium
,
Greet Van den Berghe
1  Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium
› Author Affiliations
Supported by: Methusalem Program (METH/14/06)
Supported by: Flemish Government through KU Leuven
Supported by: Greet Van den Berghe (ERC AdvG-2017–78580)
Further Information

Publication History

received 29 April 2019

accepted 28 January 2020

Publication Date:
25 March 2020 (online)

Abstract

Critically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 μg 25OHD followed by daily infusion of 15 μg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 –16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness.