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Abstract: FR-OR037

Serum Sclerostin: A Useful Biomarker of CKD-MBD

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • De maré, Annelies, University of Antwerp, Antwerp, ANTWERP, Belgium
  • D'Haese, Patrick, University of Antwerp, Antwerp, ANTWERP, Belgium
  • Behets, Geert J., University of Antwerp, Antwerp, ANTWERP, Belgium
  • Delanaye, Pierre, University of Liège, Liège, Belgium
  • Cavalier, Etienne, University of Liege, CHU Sart-Tilman, Liege, Belgium
  • Verhulst, Anja, University of Antwerp, Antwerp, ANTWERP, Belgium
  • Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium
Background

Sclerostin is a glycoprotein secreted by osteocytes and antagonizing the bone catabolic effects of the wnt/beta-catenin pathway. Mounting evidence indicates that circulating sclerostin may qualify as a biomarker of CKD-MBD. In this study we report data from a clinical study in which correlations between circulating sclerostin, skeletal sclerostin expression, bone histomorphometric parameters and serum markers of bone metabolism were investigated.

Methods

A transiliac bone biopsy was taken and serum samples were collected in a cohort of 68 ESRD patients (19 males) at the time of transplantation. Serum sclerostin levels were measured using 4 different commercially available assays (BioMedica, Diasorin, Tecomedical and R&D). Skeletal sclerostin expression was evaluated on immunohistochemically stained tissue sections by counting the % of sclerostin positive osteocytic lacunae. Quantitative bone histomorphometry was performed on Goldner stained undecalcified tissue sections. Different serum markers of bone metabolism were analysed using commercially available kits.

Results

43 ± 13% of the osteocytic lacunae were positive for sclerostin expression. Median; interquartile range (IQR) serum sclerostin concentrations (pg/ml) with the 4 assays were: 213; 159 (R&D), 1155; 848 (Diasorin), 1687; 1501 (Tecomedical), 3109; 2524 (BioMedica). Despite these large inter-assay variation, significant correlations with the skeletal sclerostin expression were found for the 4 assays under study with the Biomedica assay showing the best correlation: Rs=0.3989, p<0.001. Furthermore, both skeletal and serum (except for the Diasorin assay) sclerostin levels negatively correlated with static bone histomorphometric and serum parameters reflecting bone metabolism (formation/-turnover/-mineralization) i.e. osteoid width (p<0.05), osteoblast perimeter (p<0.05), bone-specific alkaline phosphatase (p<0.05), N-terminal propeptide of type I collagen (p<0.01), PTH (p<0.01).

Conclusion

In ESRD patients, circulating sclerostin levels significantly correlate with skeletal expression of the protein and can be regarded as a metabolic bone marker. Further research investigating extra-osseous production (e.g. calcifying vascular smooth muscle cells) of sclerostin is warranted since variation in circulating sclerostin cannot be explained by its variation in skeletal expression only.

Funding

  • Government Support - Non-U.S.