The present invention relates to uses of antagonists of Rspondin-3 (Rspo3) polypeptides or Rspondin-3 nucleic acids. The invention is based on the demonstration that partial deficiency of Rspo3 leads to a significant increase of bone mass. These results indicate a major role for Rspo3 as a bone anabolic marker or target. Thus, the invention also relates to the use of Rspo3 antagonists in the treatment of osteopenia disorders, particularly in conditions associated with increased bone resorption.