To determine the changes in bone metabolism in response to combined chemotherapy in patients with bone metastases (BM), we examined osteocalcin (BGP), alkaline-phosphatase (ALP), hydroxyproline (HYP), pyridinoline (PYR), and/or deoxypyridinoline (D-PYR) in 25 cancer patients. In patients without BM, serum BGP was normal and not affected by chemotherapy. In patients with BM, however, BGP was often abnormally high or low, and some patients reacted to chemotherapy with a BGP increase at 4 weeks after initiation of therapy. Such an increase was observed in the group of patients who responded favorably to therapy as judged by a decrease in bone pain and tumor-associated biochemical markers. Urine HYP, PYR, and D-PYR were high in patients with BM before therapy; D-PYR decreased transiently at 2 weeks and increased thereafter. We assume that increased bone-resorption markers along with increased bone formation markers after therapy would indicate recovery of coupled bone metabolism, as the deranged bone remodeling is improved by tumor-regression. This study suggests that BGP and D-PYR can be useful early markers to predict favorable bone response to chemotherapy in patients with BM.