Effect of Vitamin D Treatment on Serum Sclerostin Level

Abstract

Sclerostin is an osteocyte-secreted endogenous inhibitor of Wnt signaling. Several systemic and local factors have been suggested as possible regulators of sclerostin expression by osteocytes. In this study, we examined the effect of vitamin D treatment on sclerostin levels. 44 patients with diagnosis of vitamin D deficiency (25(OH)D≤20 ng/ml) were involved in the study. Patients had monthly intramuscular injection of 300.000 IU cholecalciferol for 3 consecutive months. Sclerostin, 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) levels were measured during the diagnosis and after the replacement of vitamin D. 8 male and 36 female patients were enrolled in the study. Minimum age, maximum age and average age were 21, 55 and 32.02±9.26 years, respectively. A statistically significant difference was observed between the pre-treatment and post-treatment values in 25(OH)D levels (p:0.001, 10.27±4.62 ng/ml and 51.40±14.62 ng/ml, respectively), PTH levels (p:0.001, 50.32±19.05 pg/ml and 33.97±13.12 pg/ml, respectively) and sclerostin levels (p:0.002, 858.98±351.63 pg/ml and 689.52±197.92 pg/ml, respectively). No statistically significant difference, however, was found between the pre-treatment and post-treatment calcium, phosphorus and ALP levels. Correlation analysis made on pre-treatment and post-treatment sclerostin levels and 25(OH)D, PTH, calcium, phosphorus and ALP levels revealed no statistically significant correlation. Our findings show that the sclerostin level of patients with vitamin D deficiency decreases considerably through treatment.

Relationship between plasma levels of sclerostin, calcium–phosphate disturbances, established markers of bone turnover, and inflammation in haemodialysis patients

“…Inconsistently, Yadav et al showed that high dose vitamin D supplementation did not affect serum sclerostin levels in non-diabetic stage G3-4 CKD patients [27]. Furthermore, Acibucu et al demonstrated even a decrease in sclerostin level during intramuscular therapy with 300.000 IU cholecalciferol injected monthly for 3 consecutive months in vitamin D deficient non-CKD patients [28]. …”

Role and mechanism of action of sclerostin in bone

“…Thus, using Saos-2 cells, Wijenayaka et al showed that 1α,25-dihydroxyvitamin D3 induces the expression of Sost/Sclerostin (57), whereas St John et al found that it decreases the transcriptional activity of the Sost promoter (52). Similarly conflicting clinical data on the effects of vitamin D status on circulating sclerostin levels have been reported (58–62). Furthermore, tumor necrosis factor alpha and Tnf-related weak inducer of apoptosis increase Sost expression (63).…”

Hormonal and systemic regulation of sclerostin

“…The results in men are consistent with those reported to occur in vitro , whereby treatment of osteogenic sarcoma SaOS2 cells with 1,25-dihydroxyvitamin D induced increases in both SOST mRNA and sclerostin protein levels [59]. In contrast to these results, however, are those in which 44 subjects with biochemically determined vitamin D deficiency (defined as a 25-hydroxyvitamin D level < 20 ng/mL) were treated with monthly intramuscular injection of 300,000 IU of vitamin D (cholecalciferol) and had a significant decline (−19.4%: P<0.01) in sclerostin levels [60]. Given the well-recognized inverse relationship between vitamin D and PTH, and the effects of PTH on sclerostin levels as described earlier in this review, it appears prudent at this time to interpret vitamin D dependent effects on sclerostin with caution.…”