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Journal of Osteoporosis
Volume 2014, Article ID 682763, 7 pages
http://dx.doi.org/10.1155/2014/682763
Research Article

Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU)

1Department of Clinical Chemistry, St Thomas’ Hospital, North Wing, Lambeth Palace Road, London SE1 7EH, UK
2Wellchild Laboratory, The Evelina Children’s Hospital, London SE1 7EH, UK
3Metabolic Bone Clinic, Department of Rheumatology, Guy’s Hospital, London SE1 9RT, UK

Received 4 July 2014; Accepted 14 November 2014; Published 24 November 2014

Academic Editor: Teruki Sone

Copyright © 2014 A. Sankaralingam et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Vitamin D is important for bone health, although high loading doses have been associated with an increase in fracture risk. The mechanisms remain uncertain. Aim. We hypothesize that supraphysiological concentrations of 1,25 (OH)2 vitamin D may inhibit formation by increasing the production of Wnt inhibitors: sclerostin and DKK1. Subjects and Methods. We measured serum sclerostin and DKK1 in 34 patients (21 F, 13 M) aged mean (SD) 61.3 (15.6) years with vitamin D deficiency/insufficiency treated with a loading dose of vitamin D2 (300,000 IU) intramuscularly. Blood samples were taken at baseline and serially up to 3 months. Results. Serum 1,25 (OH)2 vitamin D increased markedly at 3 months (mean (SD) baseline 116 (63), 3 months : 229 (142) pmol/L, ). There was a significant correlation between sclerostin and DKK1 at baseline (, ) and at 3 months (, ). A significant inverse correlation was observed between sclerostin and eGFR at 3 months (, ). Sclerostin increased significantly at 3 months (). In a multilinear regression analysis with % change in sclerostin and DKK1 as dependent variable, a positive significant association was observed with % change in 1,25 (OH)2 vitamin D (), independent of changes in PTH and following correction for confounders such as age, gender, BMI, BMD and eGFR. Conclusions. Supraphysiological concentration in 1,25 (OH)2 vitamin D achieved following a loading dose of vitamin D increases sclerostin and may inhibit Wnt signalling. This may have detrimental effects on bone.