Endocrine Abstracts

Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are antagonists of Wnt signalling, inhibiting osteoblast activity and indirectly stimulating osteoclast activity. SOST and DKK1 antibody therapy leads to increases in bone mass and bone formation. However, reported associations between plasma SOST and DKK1 concentrations and measures of bone mass and turnover are conflicting. This study in healthy older men and women (n =379; median 74.1 [IQR 71.5-77.0]y) investigated associations between plasma SOST and DKK1 and (a) BMD and BMC at the hip and femoral neck, (b) markers of bone turnover and Wnt signalling (C-terminal telopeptide (CTX), Procollagen 1 N-terminal Propeptide (P1NP), bone alkaline phosphatase (BAP), osteoprotegerin and soluble receptor activator of nuclear factor-K-B ligand (OPG, sRANKL) and (c) hormonal regulators (parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)₂D), 25 hydroxy vitamin D (25(OH)D), intact and c-terminal Fibroblast Growth Factor 23 (iFGF23, cFGF23) and KLOTHO. Associations were analysed by univariate (model 1) and multivariate linear regression with adjustment for height, weight and age (model 2) or renal function (CKD-EPI eGFR; model 3). Plasma SOST was positively associated with BMD and BMC at both sites (all P<0.001) and negatively with CTX, P1NP and BAP (all P<0.01). Associations with DKK1, OPG and RANKL were non-significant. SOST was negatively associated with 1,25(OH)₂D (P=0.002) and positively with cFGF23 and iFGF23 (P<0.001 and 0.025). Associations with PTH, 25(OH)D and KLOTHO were non-significant. Model 2 provided similar results. Adjustment for eGFR attenuated associations with 1,25(OH)₂D (P=0.06) and iFGF23 (P=0.07). Plasma DKK1 was negatively associated only with cFGF23 in univariate and multivariate models. In conclusion, plasma SOST but not DKK1 was positively associated with bone mass and negatively with markers of bone formation and resorption, suggestive of lower rate of bone turnover. This was independent of body size and renal function.