Diseases of the skeleton are very common and cause significant morbidity and mortality. Examples include osteoporosis, bone metastases from breast and prostate cancer and Paget s disease of bone. The pathogenesis of skeletal diseases is still incompletely understood and despite advances in therapeutics, new treatment modalities are needed. The long-term goal of this research program is the development of improved methods for diagnosis, prevention and treatment of bone diseases based on understanding of the molecular mechanisms responsible for normal and pathological bone metabolism using cellular, animal and human models. Current research focus includes the study of: molecular mechanisms of mesenchymal stem cell differentiation into bone and cartilage cells, a fundametal process for the development and maintenance of skeletal integrity; mechanisms responsible for the development of overt bone metastases from micrometastases in the bone marrow from breast and prostate cancer and their treatment; the role of angiogenesis in normal bone development, fracture healing and bone metastases; molecular mechanisms of growth plate development; the control of bone formation by osteoblasts and the mechanism of action of sclerostin, an osteocyte specific negative regulator of bone formation; the molecular basis of Paget s disease of bone; the long-term effects of bisphosphonates in juvenile, idiopathic, postmenopausal and secondary osteoporosis.