The present disclosure is directed to the identification that R-Spondin-1 (RSpo1) acts as a positive regulator of bone formation. Accordingly, the presently disclosed subject matter provides methods for treating and/or preventing osteoporosis or bone-related disorders, including administering a pharmaceutical composition of a therapeutically effective amount of an R-Spondin (RSpo) agonist, e.g., an RSpo protein or functional fragment thereof, peptidomimetic, nucleic acid, small molecule, or other drug candidate, to a subject, e.g., a mammal. In one exemplary embodiment, the RSpo agonist is a therapeutic vector including a nucleic acid molecule encoding RSpo protein or a functional fragment thereof. The presently disclosed subject matter also provides methods for diagnosing osteoporosis and other bone-related disorders using RSpo as a marker, as well as screening methods for identifying other proteins that are involved in bone formation.
