Long-duration spaceflight is associated with an increased risk of
urolithiasis, and the
pain caused by
urinary calculi could result in loss of human performance and mission objectives. The present study investigated the risk of
urolithiasis in astronauts during 6 months on the International Space Station, and evaluated whether the suppression of
bone resorption by the
bisphosphonate,
alendronate (ALN), can reduce the risk. A total of 17 astronauts were included into the analysis: exercise using the advanced resistive exercise device (ARED) plus weekly oral 70 mg
alendronate (ARED+ALN group, n = 7) was compared to resistive exercise alone (ARED group, n = 10). Urine volume decreased in both groups during spaceflight but recovered after return. The ARED group showed increased urinary
calcium excretion from the 15th to 30th day of spaceflight, whereas urinary
calcium was slightly decreased in the ARED+ALN group. Urinary N-terminal telopeptide (NTX) and helical
peptide (HP) of
type I collagen, as
bone resorption markers, were elevated in the ARED group during and until 0 days after spaceflight, while there was no elevation in these parameters in the ARED+ALN group. Urinary
oxalate and
uric acid excretion tended to be higher in the ARED group than in the ARED+ALN group during spaceflight. These results demonstrate that astronauts on long-duration spaceflights may be at high risk for the formation of urinary
calcium oxalate and
calcium phosphate stones through increased urinary excretion of
oxalate and
uric acid, from degraded
type I collagen, as well as of
calcium from enhanced
bone resorption. Our findings suggest that increased
bone resorption during spaceflight, as a risk factor for
urinary calculus formation, could be effectively prevented by an inhibitor of
bone resorption. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and
Mineral Research.