Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95)

Abstract

Long-term spaceflights induce bone loss as a result of profound modifications of bone remodeling, the modalities of which remain unknown in humans. We measured intact parathyroid hormone (PTH) and serum calcium; for bone formation, serum concentrations of bone alkaline phosphatase (BAP), intact osteocalcin (iBGP), and type 1 procollagen propeptide (PICP); for resorption, urinary concentrations (normalized by creatinine) of procollagen C-telopeptide (CTX), free and bound deoxypyridinoline (F and B D-Pyr), and Pyr in a 36-year-old cosmonaut (RTO), before (days −180, −60, and −15), during (from days 10 to 178, n = 12), and after (days +7, +15, +25, and +90) a 180-day spaceflight, in another cosmonaut (ASW) before and after the flight. Flight PTH tended to decrease by 48% and postflight PTH increased by 98%. During the flight, BAP, iBGP, and PICP decreased by 27%, 38%, and 28% respectively in CM1, and increased by 54%, 35%, and 78% after the flight. F D-Pyr and CTX increased by 54% and 78% during the flight and decreased by 29% and 40% after the flight, respectively. We showed for the first time in humans that microgravity induced an uncoupling of bone remodeling between formation and resorption that could account for bone loss.

Activation of nervous system development genes in bone marrow derived mesenchymal stem cells following spaceflight exposure

“…Results obtained from humans and rodents after spaceflights indicate that bone mass changes are site specific rather than evenly distributed throughout the skeleton, with the weight‐bearing bones more affected than the non‐weight‐bearing bones [Carmeliet and Bouillon, 1999]. Microgravity induces an uncoupling of bone remodeling equilibrium between bone formation and resorption, which could count for the bone loss [Caillot‐Augusseau et al, 1998]. These changes result in weakened and brittle bones prone to fracture on re‐entry and in accelerated osteoporosis, making bone deterioration a major problem obstructing the prospects of long‐duration manned spaceflight [Baldwin et al, 1996].…”

Effect of gender on bone turnover in adult rats during simulated weightlessness

“…Two-way ANOVA indicates significant effects of gender (P ϭ 0.036) and hindlimb unloading (P ϭ 0.0005), with no interaction between the 2 variables. tion and increased bone resorption (1,6,15,22,38,39). However, bone histology has not been investigated in astronauts, and the changes in biochemical markers of bone metabolism have not been entirely consistent (24).…”

Bone mechanobiology, gravity and tissue engineering: effects and insights

“…Post‐flight analysis revealed that a recovery time in normal gravity equivalent to the flight duration was insufficient to restore bone mineral density levels to the pre‐flight status (Vico et al ., ). Investigations on cosmonauts who experienced a 6‐month unloading exposure revealed that, as per 1‐month spaceflight, serum levels of ALP, osteocalcin and type I procollagen pro‐peptide were reduced (Caillot‐Augusseau et al ., ). In cosmonauts a bone mineral loss equivalent to an average of 3.5% (primarily in weight‐bearing bones) after a 16–28 weeks spaceflight was observed by means of dual energy X‐ray absorptiometry (DEXA) analysis (LeBlanc et al ., ).…”

“…However, available information indicate uncoupling of bone remodelling with enhancement of the expression of bone resorption markers, an increase in urinary collagen degradation crosslink products and a reduction in the expression of bone‐formation markers (Smith et al ., ). In agreement with an increased bone resorption, recent publications confirmed that deoxypyridinoline and the C ‐terminal peptide of type I collagen increased after a 3‐month spaceflight (Caillot‐Augusseau et al ., ; Zayzafoon et al ., ). Bone demineralization was associated with enhancement of calcium and phosphorus excretion (Zittermann et al ., ; Smith et al ., ).…”