title: Bone metabolism and renal stone risk during International Space Station missions.
abstract: Bone loss and renal stone risk are longstanding concerns for astronauts. Bone resorption brought on by spaceflight elevates urinary calcium and the risk of renal stone formation. Loss of bone calcium leads to concerns about fracture risk and increased long-term risk of osteoporosis. Bone metabolism involves many factors and is interconnected with muscle metabolism and diet. We report here bone biochemistry and renal stone risk data from astronauts on 4- to 6-month International Space Station missions. All had access to a type of resistive exercise countermeasure hardware, either the Advanced Resistance Exercise Device (ARED) or the Interim Resistance Exercise Device (iRED). A subset of the ARED group also tested the bisphosphonate alendronate as a potential anti-resorptive countermeasure (Bis+ARED). While some of the basic bone marker data have been published, we provide here a more comprehensive evaluation of bone biochemistry with a larger group of astronauts. Regardless of exercise, the risk of renal stone formation increased during spaceflight. A key factor in this increase was urine volume, which was lower during flight in all groups at all time points. Thus, the easiest way to mitigate renal stone risk is to increase fluid consumption. ARED use increased bone formation without changing bone resorption, and mitigated a drop in parathyroid hormone in iRED astronauts. Sclerostin, an osteocyte-derived negative regulator of bone formation, increased 10-15% in both groups of astronauts who used the ARED (p<0.06). IGF-1, which regulates bone growth and formation, increased during flight in all 3 groups (p<0.001). Our results are consistent with the growing body of literature showing that the hyper-resorptive state of bone that is brought on by spaceflight can be countered pharmacologically or mitigated through an exercise-induced increase in bone formation, with nutritional support. Key questions remain about the effect of exercise-induced alterations in bone metabolism on bone strength and fracture risk.
authors.affiliation: Human Health and Performance Directorate, NASA Lyndon B. Johnson Space Center, Houston, TX, USA. Electronic address: scott.m.smith@nasa.gov.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Department of Nutrition and Food Science, Nutritional Physiology, University of Bonn, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Heer
authors.affiliation: Human Health and Performance Directorate, NASA Lyndon B. Johnson Space Center, Houston, TX, USA.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Shackelford
authors.affiliation: Human Health and Performance Directorate, NASA Lyndon B. Johnson Space Center, Houston, TX, USA.
authors.forename: Jean D
authors.initials: JD
authors.lastname: Sibonga
authors.affiliation: Beth Israel Deaconess Medical Center and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Spatz
authors.affiliation: Wyle Science Technology and Engineering Group, Houston, TX, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Pietrzyk
authors.affiliation: JES Tech, Houston, TX, USA.
authors.forename: Edgar K
authors.initials: EK
authors.lastname: Hudson
authors.affiliation: Division of Space Life Sciences, Universities Space Research Association, Houston, TX, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Zwart
mesh_terms: D000328:Adult; D019386:Alendronate / Q000494:pharmacology; D018480:Astronauts; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D001842:Bone and Bones / Q000378:metabolism*; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013026:Space Flight; D018531:Spacecraft; D014893:Weightlessness / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019386:Alendronate
keywords: Anti-resorptives; Biochemical markers of bone turnover; Exercise