Abstract
The osteocytic protein sclerostin inhibits bone turnover. Serum sclerostin rises early in chronic kidney disease (CKD), but if this reflects osteocyte sclerostin production is unclear, since sclerostin is also expressed in extra-skeletal tissue. Glucocorticoid treatment impacts on serum sclerostin, but the effect on the association between serum and bone sclerostin is unknown. We sought to determine whether serum sclerostin reflects bone sclerostin in different CKD stages and how this association is influenced by glucocorticoid treatment. In a cross-sectional analysis, we investigated serum sclerostin, bone sclerostin by immunohistochemistry, and bone histomorphometry in iliac crest bone biopsies from 43 patients with CKD 3–5D, including 14 dialysis patients and 22 transplanted patients (18 kidney, 4 other). Thirty-one patients were on glucocorticoid treatment at time of biopsy. Patients with low bone turnover (bone formation rate < 97 µm²/mm²/day; N = 13) had higher median serum sclerostin levels (224.7 vs. 141.7 pg/ml; P = 0.004) and higher bone sclerostin, expressed as sclerostin positive osteocytes per bone area (12.1 vs. 5.0 Scl+ osteocytes/B.Ar; P = 0.008), than patients with non-low bone turnover (N = 28). In linear regression analyses, correcting for age, gender, dialysis status and PTH, serum sclerostin was only associated with bone sclerostin in patients not treated with glucocorticoids (r2 = 0.6, P = 0.018). For the first time, we describe that female CKD patients have higher median bone sclerostin than males (11.7 vs. 5.7 Scl+ osteocytes/B.Ar, P = 0.046), despite similar serum sclerostin levels and bone histo-morphometric parameters. We conclude that glucocorticoid treatment appears to disrupt the association of serum sclerostin with bone sclerostin in CKD.
Highlights
Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular complications [1], which are associated with vascular calcification and disorders of mineral metabolism, including disturbances of bone turnover, Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.1 3 Vol:.(1234567890)Association of Serum Sclerostin with Bone Sclerostin in Chronic Kidney Disease is Lost in...Sclerostin, a soluble protein coded by the SOST gene on chromosome 17q12-q21, reduces bone formation by inhibiting the anabolic canonical Wnt pathway in osteoblasts [7]
Serum sclerostin concentration and bone sclerostin were associated in CKD patients not on glucocorticoid treatment; supporting the concept that serum sclerostin reflects bone sclerostin
For the first time in CKD patients, we report that glucocorticoid treatment appears to disconnect the relationship between bone sclerostin and circulating sclerostin levels
Summary
Association of Serum Sclerostin with Bone Sclerostin in Chronic Kidney Disease is Lost in. Serum sclerostin decreases initially, but increases again with time from transplantation [13, 14]. Serum sclerostin is related to vascular calcification [21], SOST expression in calcified arteries is absent or very low [21], which implies that circulating sclerostin levels probably are not of vascular origin
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