Association of serum sclerostin with bone sclerostin in chronic kidney disease is lost in glucocorticoid treated patients

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 35D, 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.

Jaar van publicatie:2019

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:1

CSS-citation score:1

Auteurs:International

Authors from:Higher Education

Toegankelijkheid:Open