Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (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 producti...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Osteoporosis |
| Online Access: | http://dx.doi.org/10.1155/2014/682763 |
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| author | A. Sankaralingam R. Roplekar C. Turner R. N. Dalton G. Hampson |
| author_facet | A. Sankaralingam R. Roplekar C. Turner R. N. Dalton G. Hampson |
| author_sort | A. Sankaralingam |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eb27113d4ba445d797d6cdc00fbb748b |
| institution | Kabale University |
| issn | 2090-8059 2042-0064 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Osteoporosis |
| spelling | doaj-art-eb27113d4ba445d797d6cdc00fbb748b2025-02-03T01:10:19ZengWileyJournal of Osteoporosis2090-80592042-00642014-01-01201410.1155/2014/682763682763Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU)A. Sankaralingam0R. Roplekar1C. Turner2R. N. Dalton3G. Hampson4Department of Clinical Chemistry, St Thomas’ Hospital, North Wing, Lambeth Palace Road, London SE1 7EH, UKDepartment of Clinical Chemistry, St Thomas’ Hospital, North Wing, Lambeth Palace Road, London SE1 7EH, UKWellchild Laboratory, The Evelina Children’s Hospital, London SE1 7EH, UKWellchild Laboratory, The Evelina Children’s Hospital, London SE1 7EH, UKDepartment of Clinical Chemistry, St Thomas’ Hospital, North Wing, Lambeth Palace Road, London SE1 7EH, UKBackground. 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.http://dx.doi.org/10.1155/2014/682763 |
| spellingShingle | A. Sankaralingam R. Roplekar C. Turner R. N. Dalton G. Hampson Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) Journal of Osteoporosis |
| title | Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) |
| title_full | Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) |
| title_fullStr | Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) |
| title_full_unstemmed | Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) |
| title_short | Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) |
| title_sort | changes in dickkopf 1 dkk1 and sclerostin following a loading dose of vitamin d2 300 000 iu |
| url | http://dx.doi.org/10.1155/2014/682763 |
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