Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines

Abstract

Background: Dry immersion (DI), a ground-based model of microgravity previously used in Russia, has been recently implemented in France. The aim of this study was to analyze early events in a short-term DI model in which all conditions are met to investigate who is first challenged from osteo- or adipo-kines and to what extent they are associated to insulin-regulating hormones.

Methods: Twelve healthy men were submitted to a 3-day DI. Fasting blood was collected during pre-immersion phase for the determination of the baseline data collection (BDC), daily during DI (DI24h, DI48H and DI72h), then after recovery (R+3h and R+24h). Markers of bone turnover, phosphocalcic metabolism, adipokines and associated factors were measured.

Results: Bone resorption as assessed by tartrate-resistant acid phosphatase isoform 5b and N-terminal crosslinked telopeptide of type I collagen levels increased as early as DI24h. At the same time, total procollagen type I N- and C-terminal propeptides and osteoprotegerin, representing bone formation markers, decreased. Total osteocalcin [OC] was unaffected, but its undercarboxylated form [Glu-OC] increased from DI24h to R+3h. The early and progressive increase in bone alkaline phosphatase activities suggested an increased mineralization. Dickkopf-1 and sclerostin, as negative regulators of the Wnt-β catenin pathway, were unaltered. No change was observed either in phosphocalcic homeostasis (calcium and phosphate serum levels, 25-hydroxyvitamin D, fibroblast growth factor 23 [FGF23]) or in inflammatory response. Adiponectemia was unchanged, whereas circulating leptin concentrations increased. Neutrophil gelatinase-associated lipocalin [lipocalin-2], a potential regulator of bone homeostasis, was found elevated by 16% at R+3h compared to DI24h. The secretory form of nicotinamide phosphoribosyl-transferase [visfatin] concentrations almost doubled after one day of DI and remained elevated. Serum insulin-like growth factor 1 levels progressively increased. Fasting insulin concentrations increased during the entire DI, whereas fasting glucose levels tended to be higher only at DI24h and then returned to BDC values. Changes in bone resorption parameters negatively correlated with changes in bone formation parameters. Percent changes of ultra-sensitive C-reactive protein positively correlated with changes in osteopontin, lipocalin-2 and fasting glucose. Furthermore, a positive correlation was found between changes in FGF23 and Glu-OC, the two main osteoblast-/osteocyte-derived hormones.

Conclusion: Our results demonstrated that DI induced an unbalanced remodeling activity and the onset of insulin resistance. This metabolic adaptation was concomitant with higher levels of Glu-OC. This finding confirms the role of bone as an endocrine organ in humans. Furthermore, visfatin for which a great responsiveness was observed could represent an early and sensitive marker of unloading in humans.

Fig 1. Description of the study.

A Time line of the experiment with the timing of different blood samples. Blue area corresponds to the DI phase. BDC: baseline data collection; DI: dry immersion; R: recovery. B A volunteer in the DI bath.

Fig 2. Effect of dry immersion on bone metabolism.

Changes in bone resorption (at left) and formation or mineralization (at right) markers during dry immersion. Values are expressed as medians ± interquartile range for n = 12 except for NTx* which was made for n = 6 only. a,b,c indicate significant differences vs. BDC, DI_24h and DI_48h, respectively. CTx: C-terminal crosslinked telopeptide of type I collagen; NTx: N-terminal crosslinked telopeptide of type I collagen; TRAP5b: tartrate-resistant acid phosphatase isoform 5b; P1CP: procollagen type I C-terminal propeptide; P1NP: procollagen type I N-terminal propeptide; bAP: bone alkaline phosphatase.

Fig 3. Effect of dry immersion on the different forms of osteocalcin and on the insulinic response.

At Top, changes in carboxylated (Gla-OC) and decarboxylated (Glu-OC) forms of osteocalcin during dry immersion. At middle, changes in values of glucose and insulin during dry immersion. At bottom, changes in values of IGF1 and visfatin during dry immersion. Values are medians ± interquartile range for n = 12. a,b,c indicate significant differences vs. BDC, DI_24h and DI_48h, respectively; a’ different vs. BDC p<0.10.

Fig 4. Association between biochemical blood markers.

Spearman correlations between percent changes at DI_48h in bone and energy metabolism parameters for n = 12 except for NTx* which was made for n = 6 only. Changes are expressed in percent from BDC. OPN: osteopontin; usCRP: ultrasensitive C-reactive protein; P1CP: procollagen type I C-terminal propeptide; CTx: C-terminal crosslinked telopeptide of type I collagen; OC: osteocalcin; Gal-OC and Glu-OC: carboxylated and uncarboxlalted forms of OC, respectively; NTx: N-terminal crosslinked telopeptide of type I collagen; usCRP: ultrasensitive C-reactive protein; FGF23: fibroblast growth factor 23.