Context: The role and importance of circulating sclerostin is poorly understood. High Bone Mass (HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. Objective: To determine circulating sclerostin concentrations in HBM. Design: Case-control study Participants: 406 HBM index cases were identified by screening DXA databases from 4 UK centers (n=219,088), excluding significant osteoarthritis/artefact. Controls comprised unaffected relatives & spouses. Main measure(s): Plasma sclerostin, lumbar spine L1, total hip and total body DXA, and radial and tibial pQCT (subgroup only). Results: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases, compared with controls; mean[SD] 130.1[61.7] and 88.0[39.3], vs. 66.4[32.3]pmol/L, both p<0.001, which persisted after adjustment for a priori confounders. In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (i.e. L1, total hip and total body DXA BMD, and radial/tibial cortical area, cortical BMD and trabecular density). Whilst these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particular for radial trabecular density (interaction p<0.01). Conclusions: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/pQCT parameters, genetic factors predisposing to HBM may contribute to increased sclerostin levels.