Mounting evidence indicates that sclerostin, a well-known inhibitor of bone formation, may qualify as a clinically relevant
biomarker of
chronic kidney disease-related
mineral and bone disorder (
CKD-MBD), including abnormal
mineral and bone metabolism and extraskeletal calcification. For this purpose, in this study we investigate the extent to which circulating sclerostin, skeletal sclerostin expression, bone histomorphometric parameters, and
serum markers of bone metabolism associate with each other. Bone biopsies and serum samples were collected in a cohort of 68
end-stage kidney disease (ESKD) patients. Serum sclerostin levels were measured using 4 different commercially available assays. Skeletal sclerostin expression was evaluated on immunohistochemically stained bone sections. Quantitative bone histomorphometry was performed on Goldner stained tissue sections. Different
serum markers of bone metabolism were analyzed using in-house techniques or commercially available assays. Despite large inter-assay differences for circulating sclerostin, results obtained with the 4 assays under study closely correlated with each other, whilst moderate significant correlations with skeletal sclerostin expression were also found. Both skeletal and circulating sclerostin negatively correlated with histomorphometric bone and serum parameters reflecting bone formation and turnover. In this study, the unique combined evaluation of bone sclerostin expression, bone histomorphometry, bone
biomarkers, and serum sclerostin levels, as assessed by 4 different assays, demonstrated that sclerostin may qualify as a clinically relevant marker of disturbed bone metabolism in ESKD patients.