Osteoporosis is characterized by low bone mass and deterioration of bone tissue that increase skeletal fragility and risk of fracture. Remodelling of skeletal tissue is related to biochemical processes that regulate osteoclastic and osteoblastic activity regukating bone mineral resorption and formation. The purpose of this study was to measure plasma-based markers of bone remodelling in relation to whole-body bone mineral density in humans. Healthy young (n=172 aged 18-30 yrs) and healthy older (n=283, aged 69-80 yrs) men and women were recruited as part of the EU FP7 project MYOAGE; a multi-centre and multi-national cross-sectional study of musculoskeletal ageing. All participants provided written informed consent to the study. Whole body bone mineral density was assessed in the fasted state by dual-energy x-ray absorptiometry (DEXA). Resting, fasted 10 ml blood samples were collated into EDTA tubes. Plasma concentrations of selected analytes were determined with the Multiplex xMAP “Human Bone Magnetic Bead” assay or ELISA and a Luminex 200 Bioanalyser. Multivariate ANOVA and regression analyses were used to identify age- and sex-differences and correlations between analytes and bone mineral density. Regressions were adjusted for Country and Body Composition. Whole-body bone mineral density was significantly lower in women compared with men (11.4% difference) and lower in old compared with young (9.0% difference) (p<0.001). Older participants had significantly higher concentrations of Osteoprotegrin (OPG) (70% greater), Osteopontin (OPN) (3.2% greater) and Sclerostin (SOST) (83.7 % greater) compared with young. In young men and women, Dickkopf-1 (DKK1) and Vitamin D (Vit D) were significantly associated with bone mineral density. In older men, significant correlations were found for bone mineral density and DKK1 (r=0.184), OPN (r=0.201), SOST (r=0.251) and Vit D (r=0.296). In older women, associations were found for bone mineral density and DKK1 (r=0.178), SOST (r=0.262) and Vit D (r=-0.233). These results identify plasma-based markers of bone remodelling in healthy ageing. Vit D was associated with bone mineral density, although the association was positive in older men but inverse in older women. DKK1 and SOST were consistently associated with bone mineral density in older men and women. These proteins are Wnt-pathway inhibitors that are also up-regulated in bone diseases (Ke et al. Endocrinol Rev. 2012).