Responsiveness of osteoblastic and osteolytic bone metastases to vitamin D analogs

Bone is the primary site of metastases in advanced androgen-independent prostate cancer. These metastases are primarily bone-forming, although the presence of osteolytic response has also been reported. Bone-homing therapy is a strategy based on the popular seed-and-soil relationship between the epithelial malignant cells and the bone stroma. Calcitriol (1,25-dihydroxyvitamin D3) and its synthetic analogs (deltanoids) are drugs that have a direct effect on both the skeleton and the invading metastatic cells and, therefore, are considered useful in the treatment of advanced prostate cancer. In this article, I review the nature of the response induced by the malignant cells in the bone (bone formation or bone resorption) and how it affects the outcome of a vitamin D analog treatment in preclinical models of metastatic bone disease.