Methods and pharmaceutical compositions of use in regulation of mammalian bone-forming activities of SFRPs (secreted frizzled-related proteins) are disclosed. SFRPs are secreted receptors for Wnts, which are important polypeptide growth factors that are known to regulate fundamental biological processes such as tissue polarity, embryonic development, and tumorigenesis. Methods can be used to identify compounds which target the Wnt-antagonizing function of an SFRP by way of one or more domains or specific amino acids. Pharmaceutical compositions can be prepared using these compounds, and bone disorders can be treated using these pharmaceutical compositions.