Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300, 000 IU). (7th December 2014)

• Record Type: Journal Article
• Authors: Sankaralingam, A.; Roplekar, R.; Turner, C.; Dalton, R. N.; Hampson, G.
• Other Names: Sone Teruki Academic Editor.
• Is Part Of: Journal of osteoporosis. Volume 2014(2014)
• Publication Date: 2014-12-07
• Subjects: Osteoporosis -- Periodicals; Osteoporosis; Orthopedic Procedures; Osteoporosis; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.716
• DOI: 10.1155/2014/682763
• Languages: English
• ISSNs: 2090-8059

Abstract

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, P < 0.001 ). There was a significant correlation between sclerostin and DKK1 at baseline (r = 0.504, P = 0.002 ) and at 3 months (r = 0.42, P = 0.013 ). A significant inverse correlation was observed between sclerostin and eGFR at 3 months (r = - 0.494, P = 0.007 ). Sclerostin increased significantly at 3 months (P = 0.033 ). 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 (P = 0.038 ), 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.