Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D-2 (300,000 IU)

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, 13M) aged mean (SD) 61.3 (15.6) years with vitamin D deficiency/insufficiency treated with a loading dose of vitamin D-2 (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 inhibitWnt signalling. This may have detrimental effects on bone.