title: Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station.
abstract: Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption.
  
  
  BACKGROUND
  Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity.
  
  
  METHODS
  We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined.
  
  
  RESULTS
  Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01).
  
  
  CONCLUSIONS
  These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.
authors.affiliation: Human Adaptation and Countermeasures Office, NASA Lyndon B. Johnson Space Center, Houston, TX 77058, USA. scott.m.smith@nasa.gov
authors.forename: Scott M
authors.initials: SM
authors.lastname: Smith
authors.forename: Meryl E
authors.initials: ME
authors.lastname: Wastney
authors.forename: Kimberly O
authors.initials: KO
authors.lastname: O'Brien
authors.forename: Boris V
authors.initials: BV
authors.lastname: Morukov
authors.forename: Irina M
authors.initials: IM
authors.lastname: Larina
authors.forename: Steven A
authors.initials: SA
authors.lastname: Abrams
authors.forename: Janis E
authors.initials: JE
authors.lastname: Davis-Street
authors.forename: Victor
authors.initials: V
authors.lastname: Oganov
authors.forename: Linda C
authors.initials: LC
authors.lastname: Shackelford
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry; D000704:Analysis of Variance; D018480:Astronauts; D015415:Biomarkers; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D003094:Collagen / Q000737:chemistry; D024042:Collagen Type I; D006801:Humans; D007700:Kinetics; D015675:Osteocalcin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D013026:Space Flight; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism; D014893:Weightlessness
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium