Leading Light, a chemiluminescent-based binding assay, has been developed to permit the high-throughput screening of sclerostin inhibitors without the need for cell lines or transfection. The assay contains human sclerostin immobilized to a 96-well plate, and uses an engineered LRP5-alkaline phosphatase (AP) conjugate. LRP5-AP binds immobilized sclerostin, producing signal in the development step. Signal decreases when this interaction is blocked by the presence of a sclerostin inhibitor. This system can be used for drug screening to identify small molecule compounds, antibodies, DNA aptamers, and peptides capable of modulating the sclerostin-LRP interaction. Initial screening of sclerostin inhibitors can occur in less than 2.5 hours.