Bone loss and urolithiasis are inevitable outcome in human space flight and long-duration bet rest. The rate of space flight induced bone loss is 10 times faster than in those with osteoporosis. Significant bone loss at weight bearing bones, elevated urinary calcium excretion, and un-coupling of bone resorption and bone formation are observed during the long-term bed rest study. Improvements of resistive exercise device and vitamin-D supplementation for astronauts in International Space Station can partially maintain bone mass, however, they can not fully supress bone resorption and urinary calcium excretion during space flight. JAXA and NASA are performing joint study to validate the mitigration effects on bone resorption and urolithiasis of bisphosphonate supplement in conjunction with excercise.