#3069 CIRCULATING SCLEROSTIN AFFECTS URINARY CALCIUM EXCRETION AMONG STONE FORMERS

Abstract Background and Aims Sclerostin plays an important role in bone metabolism and adipose tissue. Experimental studies suggest that sclerostin also influences urinary calcium excretion (Uca), but this relationship has not been addressed in humans. We aimed to study the association of UCa levels with serum sclerostin, bone mineral density (BMD) and body composition among stone-formers (SF). Method We retrieved data from patient records, including clinical characteristics, nutritional, biochemistry and hormonal data as well as BMD and body composition determined by dual energy X-ray absorptiometry. Serum sclerostin levels were measured using ELISA kits. Determinants of UCa were studied using multivariate linear regression. Results A total of 107 SF (35.8 ± 9.3 years, 54% male) with eGFR of 99.8 ± 14.5 mL/min/1.73 were included. The subjects were divided by sex and clustered into tertiles according to UCa as shown in Table 1. Men in the highest UCa tertile had higher body mass index (BMI) and serum sclerostin levels, were more likely to have hypertension and metabolic syndrome, had lower lean mass, a trend towards higher fat mass (p = 0.06), and no statistical differences in BMD. Women in the highest UCa tertile had higher BMI and a trend towards higher serum sclerostin levels (p = 0.06), were more likely to have hypertension and metabolic syndrome, with no differences in BMD. Sclerostin was positively correlated with fat mass (r = 0.38, p = 0.004) and inversely correlated with lean mass (r = -0.32, p = 0.01) among men, but not among women. To further adjust for the influence of weight load on BMD for both sexes, the latter was also expressed as a ratio per BMI (BMD/BMI). Although lumbar spine BMD/BMI was inversely associated with UCa (β -0.26, p = 0.01) in univariate analysis, it lost significance in the multivariate model (Table 2). Hypertension, metabolic syndrome and serum sclerostin were independent determinants of UCa (Table 2). Conclusion Present findings disclosed that serum sclerostin, hypertension and metabolic syndrome were independent determinants of urinary calcium in stone formers. These data suggest that in addition to the hormones traditionally thought to alter calcium reabsorption in the kidney, sclerostin may play a significant additional role, warranting further intervention studies in order to test potential medication strategies to reduce calciuria in this population.