Endocrine Abstracts

Background: Bone turnover markers are used in research and clinical practice, but only in part reflect bone formation and resorption. Components of the Wnt-signaling pathway, regulating osteoblastogenesis and osteoblast function, can be measured in serum, however it is unclear whether they reflect underlying bone mass and metabolism.

Objective: Determine whether serum levels of Wnt-signalling components reflect bone mass or metabolism in men during growth and after attaining peak bone mass age.

Methods: Sclerostin, DKK-1 and OPG were measured in 108 healthy males (34.2±4.9 years) from the SIBLOS cohort and 122 peri-pubertal boys from the NINIOS cohort (12.5±2.8 years) using the quantitative sandwich ELISA method developed by Biomedica. Procollagen type 1 N-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX) and osteocalcin were measured using ECLIA (Roche Diagnostics) in the SIBLOS cohort only. Dual-energy x-ray absorptiometry (Hologic) determined body composition and bone mineral content (BMC) at the whole-body and lumbar spine.

Results: In NINIOS, DKK-1 concentrations were higher than in SIBLOS (54.05 pmol/l, 33.45 pmol/l, respectively; P< 0.001), whereas OPG levels were non-significantly lower (3.50 pmol/l, 3.76 pmol/l, respectively; P=0.07). No differences were found for sclerostin. No association between lumbar or whole-body BMC with Wnt-signalling parameters was found. In SIBLOS, no associations were found between P1NP, CTX, and osteocalcin on the one hand and sclerostin, OPG and DKK-1 on the other hand.

Conclusion: Serum levels of sclerostin, OPG and DKK-1 were not related to bone mass in either peri-pubertal boys or adult men. Further, in adult men, they did not associate with P1NP, CTX or osteocalcin. However, as peri-pubertal boys showed higher levels of DKK-1 than adult men, DKK-1 being reflective for bone modelling cannot be ruled out. This will be addressed in the longitudinal part of the NINIOS study and by determining P1NP, CTX and osteocalcin in the NINIOS cohort.