ECTS Abstracts (2015) 1 P312

Sclerostin and Dickkopf1 (DKK1) Expression in Bone in Relation to Bone Metabolism

Dirk-Jan Mons, Angela Oostlander, Huib van Essen, Annemieke Heijboer, Ad van Bodegraven, Paul Lips & Nathalie Bravenboer

VU University Medical Center, Amsterdam, The Netherlands.

Background: Osteocytes produce sclerostin and DKK1. Sclerostin and DKK1 are well known antagonists of the canonical wnt signalling pathway and thereby inhibitors of osteoblast function. At tissue level, the role of DKK1 and sclerostin expression on bone structure and turnover is not well established. The aim of this study is to identify the relationship between DKK1 and sclerostin expression in bone tissue and markers of bone formation and bone structure.

Methods: Men (n=18) and women (n=20) with quiescent Crohns disease and DXA-assessed osteopenia participated in this double blind clinical trial (NTR 163). Transiliac bone biopsies were obtained. Sclerostin and DKK1 expression was detected using immunohistochemistry and quantified by detection of positively stained osteocytes as a percentage of total number of osteocytes/mm2. Standardised histomorphometry was performed to analyse bone formation and structure. A Pearson correlation coefficient was calculated to test the association between sclerostin and DKK1 expression and histomorphometric indices for bone mass and turnover.

Results: No significant correlation between sclerostin and DKK1 expression in trabecular bone (r=-0,17 P=0,29) was found. In patients with a higher bone volume sclerostin expression in trabecular bone osteocytes was higher (r=0,53 P=0,0007) while DKK1 expression decreased (r=-0,36 P=0,03). DKK1 expression in trabecular bone osteocytes was negatively associated with bone formation rate: r=-0,36 P=0,03.

Conclusions: Although sclerostin and DKK1 are both inhibitors of osteoblast differentiation, their relationship with bone volume is reversed. Possibly high levels of sclerostin inhibit DKK1 expression either directly or indirectly via lower bone formation, however an association between sclerostin and DKK1 expression was not observed. Only a higher DKK1 expression was associated with a lower bone formation. In conclusion, our study suggests that sclerostin expression reflects mainly bone mass while DKK1 expression represents mainly bone formation.

Disclosure: The authors declared no competing interests.

Article tools

My recent searches

No recent searches.