Space Flight Is Associated with Rapid Decreases of Undercarboxylated Osteocalcin and Increases of Markers of Bone Resorption without Changes in Their Circadian Variation: Observations in Two Cosmonauts

Abstract

Background: Microgravity induces bone loss by mechanism(s) that remain largely unknown. Methods: We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. Results: During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. Conclusion: Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

“…(Bottom) Significant calcium kinetic study findings: intake ( ), absorption (+), and resorption (×). The x-axis labels match the collection profiles for the blood data; the only difference for urine data was that these were completed at R + 5-9 (instead of 5-10) and R + 10-16 days (instead of [11][12][13][14][15][16][17].…”

“…Effective countermeasures that reduce bone loss will not only help ensure the health and safety of crews on shorter missions (such as those used for the International Space Station) but will also contribute to the development of treatments for bone diseases on Earth. (1,11,12) Bone resorption, assessed by measuring urinary concentrations of collagen cross-links (7,(13)(14)(15)(16) or hydroxyproline, (6,17) is greater during space flight than before flight. Initial calcium tracer kinetic studies conducted on Mir also indicated that bone resorption increases during flight, (7) despite use of exercise countermeasures.…”

Physiological, Pharmacokinetic, and Pharmacodynamic Changes in Space

“…135 Vitamin K metabolism and action may also be affected in microgravity. 136 Riepl et al 137 observed altered levels of several gastroenteropancreatic peptides during both the initial phase of exposure and after 4 weeks of space flight. Maccarrone et al 138,139 observed that the catalytic efficiency and affinity of soybean lipooxygenase-I (LOX-1) on linoleic acid was four times higher in flight than on ground.…”

Pulsed Electromagnetic Fields Partially Preserve Bone Mass, Microarchitecture, and Strength by Promoting Bone Formation in Hindlimb-Suspended Rats

“…(3)(4)(5) Studies also showed that crewmembers during spaceflight experienced reduced bone formation, augmented bone resorption, and persistently higher fracture risk even 1 year after returning to Earth. (6,7) Similarly, mechanical unloading also led to significant BMD decrease and concomitant higher incidence of bone fractures for patients with long-term bed rest or immobilization. (8,9) In view of the side effects or high cost of antiosteoporosis drugs (eg, calcitonin, hormones, and calcium and vitamin D preparations), (10)(11)(12)(13)(14) safe and noninvasive biophysical countermeasures for disuse osteoporosis might be more promising in clinical application, and especially favorable for the use of spaceflight.…”