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.Introduction: 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. Materials and 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.

Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

“…Spaceflight decreases trabecular indices of bone formation in the iliac crest of monkeys [37,38], and human astronauts experience an imbalance in bone resorption and bone formation during spaceflight [2,39], which probably causes the cortical bone loss that is observed after 4-6 months in space [40,41]. Similarly, patients with acute spinal cord injury (< 6 months postinjury) experience increased bone resorption and increased urinary calcium excretion, which likely explains why spinal cord injury patients lose bone structural properties and demonstrate increased rates of bone fracture [12,16,42,43].…”

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes

“…This follows because the abundances of Ca isotopes in urine and soft tissue represent the net effect of changes in bone formation and resorption and Ca excretion integrated over the 2-to 3-d residence time of Ca in soft tissue compartments (21,22). In contrast, each biochemical marker reflects only one process (either bone resorption or formation).…”

“…In the first study, Smith et al (21) estimated rates of new bone formation of 190-635 mg Ca/d for male and female volunteers. In a follow-up study, the work by Smith et al (22) estimated the rate of bone formation of 16 astronauts at 490 ± 153 mg Ca/d before spaceflight and 434 ± 194 mg Ca/d during spaceflight. F diet .…”

Recovery of spaceflight-induced bone loss: Bone mineral density after long-duration missions as fitted with an exponential function

“…Studies using calcium kinetics, site-specific bone densitometry and bone turnover markers document a net loss of bone mineral in the gravitationally-unloaded skeleton of crew members who had flown either on Skylab (28, 56 and 84 days) or on long-duration missions (>4 months) aboard the Russian Mir spacecraft and the International Space Station (ISS) [2][3][4][5][6][7][8][9][10][11][12].…”