The invention provides mutant SH3-binding protein (SH3BP2) nucleic acids, polypeptides, and agents which selectively bind to the mutant SH3BP2 molecules and which do not bind to the wild type SH3BP2 molecules. Methods for selecting agents which inhibit mutant SH3BP2 expression, as well as diagnostic and therapeutic methods which utilize the mutant SH3BP2 molecules for diagnosing and treating disorders of bone homeostasis, also are provided.