Association of Circulating Sclerostin With Bone Mineral Mass, Microstructure, and Turnover Biochemical Markers in Healthy Elderly Men and Women

Context: Sclerostin inhibits bone formation and is involved in the bone response to mechanical loading, but the role and significance of circulating sclerostin are poorly understood. Objective: We assessed the association between serum sclerostin and calcitropic hormones, bone turnover marker levels, bone mineral content/density, and microstructure using 3 different immunoassays. Design, Setting, and Participants: In a cross-sectional study, serum sclerostin was measured in a cohort of 187 healthy subjects (98 women; 89 men) aged 65 +/- 1 (+/- SD) years. Results: Overall, mean sclerostin (95% confidence interval) was 37.3 (18.0-69.2) ng/L, 1165.8 (464.0-2296.4) ng/L, and 513.5 (250.7-950.9) ng/L with assays I, II, and III, respectively. Serum sclerostin was higher in men with assays II and III. In all 3 assays, sclerostin and PTH were inversely correlated, only after adjustment for whole-body bone mineral content (WB-BMC). After adjustment for sex and WB-BMC, the bone turnover markers amino-terminal propeptide of type I rocollagen and carboxyterminal cross-linked telopeptide of type I collagen negatively correlated only with assay II. In all 3 assays, sclerostin positively correlated to WB-BMC, the distal radius and the distal tibia cortical area, cancellous bone volume and trabecular number, and lumbar spine and proximal femur areal bone mineral density after adjustment for sex. Conclusion: Sclerostin levels are markedly different according to the immunoassay used. Detection of an association with calcitropic hormones or turnover markers relies on the epitope recognized by the immunoassay and adjustment for bone mass.