Abstract Background and Aims Reduced bone mineral density (BMD) has been observed in stone-formers (SF). Although obesity is considered a protective factor for bone health due to increased mechanical load, the role of muscle mass (lean) or body fat remains controversial. Sclerostin, an antagonist of the Wnt signaling pathway, is secreted by osteocytes and its actions involve the inhibition of bone formation, FGF23 stimulation, and increased urinary calcium and phosphorus excretion. Recent studies also indicate its association with body composition. The aim of the present study was to evaluate the relationship between BMD and body composition with serum sclerostin levels in male SF. Method This is a retrospective study, based on medical records of SF with available data of BMD and body composition, serum and urinary biochemistry and hormonal measurements including sclerostin. BMD had been assessed at lumbar spine (L1-L4), femoral neck (FN) and total femur (TF) and body composition (fat and lean mass) in a dual energy X-ray absorptiometry (DXA). Results Fifty-five male SF (37.2 ± 9.3 years) were included. Patients were divided into tertiles according to the percentage of body fat (T1, n = 19, 8.7-20.0 %; T2, n = 20, 20.1-26.0 %; T3, n = 16, 26.1-38.0 %). There was no statistical difference in BMD in any of the sites between these tertiles. Higher urinary sodium and serum sclerostin were observed in T3 versus T1 (280 ± 93 vs 199 ± 75 mEq/day, p <0.05; 33.6 ± 14.7 vs 24.7 ± 8.3 pmol/L, p<0.05, respectively). There was an inverse association between serum sclerostin and lean mass (β= -0.30, p=0.001) and direct association with fat mass (β=0.40, p=0.001), urinary calcium and phosphorus (β=0.29, p=0.02; β=0.32, p=0.01). In a multivariate linear regression model, lean mass was an independent predictor of BMD at L1-L4, FN and TF (β= 0.70, p<0.001; β=0.70, p<0.001; β=0.57, p=0.00, respectively) and at the TF there was also an inverse association between body fat and PTH (β= –0.51, p= 0.03; β= –0.25, p= 0.03). Conclusion These data suggest that male SF with a higher percentage of body fat had higher levels of serum sclerostin, which were directly associated with calciuria and phosphaturia but not with BMD. In addition, lean mass was an independent predictor of BMD. Further studies are needed to determine long-term effects of serum sclerostin levels upon bone formation in SF.