Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Aug 12

PMID 35955775

Authors

Ronni Baran

Markus Wehland

Herbert Schulz

Martina Heer

Manfred Infanger

Daniela Grimm

Affiliations

Soon will be listed here.

Abstract

Space travelers are exposed to microgravity (µ), which induces enhanced bone loss compared to the age-related bone loss on Earth. Microgravity promotes an increased bone turnover, and this obstructs space exploration. This bone loss can be slowed down by exercise on treadmills or resistive apparatus. The objective of this systematic review is to provide a current overview of the state of the art of the field of bone loss in space and possible treatment options thereof. A total of 482 unique studies were searched through PubMed and Scopus, and 37 studies met the eligibility criteria. The studies showed that, despite increased bone formation during µ, the increase in bone resorption was greater. Different types of exercise and pharmacological treatments with bisphosphonates, RANKL antibody (receptor activator of nuclear factor κβ ligand antibody), proteasome inhibitor, pan-caspase inhibitor, and interleukin-6 monoclonal antibody decrease bone resorption and promote bone formation. Additionally, recombinant irisin, cell-free fat extract, cyclic mechanical stretch-treated bone mesenchymal stem cell-derived exosomes, and strontium-containing hydroxyapatite nanoparticles also show some positive effects on bone loss.

Citing Articles

Exosomal non-coding RNAs in the regulation of bone metabolism homeostasis: Molecular mechanism and therapeutic potential.

Huang C, Xiao Y, Qing L, Tang J, Wu P Heliyon. 2025; 11(2):e41632.

PMID: 39911437 PMC: 11795052. DOI: 10.1016/j.heliyon.2025.e41632.

Proteomic and ubiquitinome analysis reveal that microgravity affects glucose metabolism of mouse hearts by remodeling non-degradative ubiquitination.

Zhang X, Zhou X, Tu Z, Qiang L, Lu Z, Xie Y PLoS One. 2024; 19(11):e0313519.

PMID: 39541295 PMC: 11563481. DOI: 10.1371/journal.pone.0313519.

Angelicae dahuricae radix alleviates simulated microgravity induced bone loss by promoting osteoblast differentiation.

Liang X, Jiang S, Su P, Yin C, Jiang W, Gao J NPJ Microgravity. 2024; 10(1):91.

PMID: 39353918 PMC: 11445575. DOI: 10.1038/s41526-024-00433-0.

Omics Studies of Specialized Cells and Stem Cells under Microgravity Conditions.

Abdelfattah F, Schulz H, Wehland M, Corydon T, Sahana J, Kraus A Int J Mol Sci. 2024; 25(18).

PMID: 39337501 PMC: 11431953. DOI: 10.3390/ijms251810014.

Melatonin Regulates Osteoblast Differentiation through the m6A Reader hnRNPA2B1 under Simulated Microgravity.

Sun Q, Xu L, Hu Z, Liu J, Yu T, Li M Curr Issues Mol Biol. 2024; 46(9):9624-9638.

PMID: 39329924 PMC: 11430354. DOI: 10.3390/cimb46090572.

References

Kimble R, Bain S, Pacifici R . The functional block of TNF but not of IL-6 prevents bone loss in ovariectomized mice. J Bone Miner Res. 1997; 12(6):935-41. DOI: 10.1359/jbmr.1997.12.6.935. View

Keshawarz N, Recker R . Expansion of the medullary cavity at the expense of cortex in postmenopausal osteoporosis. Metab Bone Dis Relat Res. 1984; 5(5):223-8. DOI: 10.1016/0221-8747(84)90063-8. View

Cabahug-Zuckerman P, Frikha-Benayed D, Majeska R, Tuthill A, Yakar S, Judex S . Osteocyte Apoptosis Caused by Hindlimb Unloading is Required to Trigger Osteocyte RANKL Production and Subsequent Resorption of Cortical and Trabecular Bone in Mice Femurs. J Bone Miner Res. 2016; 31(7):1356-65. PMC: 5488280. DOI: 10.1002/jbmr.2807. View

Talaulikar V, Chambers T, Manyonda I . Exploiting the antioxidant potential of a common vitamin: could vitamin C prevent postmenopausal osteoporosis?. J Obstet Gynaecol Res. 2011; 38(1):253-7. DOI: 10.1111/j.1447-0756.2011.01629.x. View

Sibonga J, Spector E, Keyak J, Zwart S, Smith S, Lang T . Use of Quantitative Computed Tomography to Assess for Clinically-relevant Skeletal Effects of Prolonged Spaceflight on Astronaut Hips. J Clin Densitom. 2019; 23(2):155-164. DOI: 10.1016/j.jocd.2019.08.005. View

Finkelstein J, Brockwell S, Mehta V, Greendale G, Sowers M, Ettinger B . Bone mineral density changes during the menopause transition in a multiethnic cohort of women. J Clin Endocrinol Metab. 2007; 93(3):861-8. PMC: 2266953. DOI: 10.1210/jc.2007-1876. View

Liu J, Kung A, Pheng C, Zhu H, Zhang Z, Wu Y . Efficacy and safety of 2 g/day of strontium ranelate in Asian women with postmenopausal osteoporosis. Bone. 2009; 45(3):460-5. DOI: 10.1016/j.bone.2009.05.014. View

Smith S, McCoy T, Gazda D, Morgan J, Heer M, Zwart S . Space flight calcium: implications for astronaut health, spacecraft operations, and Earth. Nutrients. 2012; 4(12):2047-68. PMC: 3546622. DOI: 10.3390/nu4122047. View

Girasole G, Jilka R, Passeri G, Boswell S, Boder G, Williams D . 17 beta-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J Clin Invest. 1992; 89(3):883-91. PMC: 442934. DOI: 10.1172/JCI115668. View

10.

He B, Zhu Y, Cui H, Sun B, Su T, Wen P . Comparison of Necroptosis With Apoptosis for OVX-Induced Osteoporosis. Front Mol Biosci. 2022; 8:790613. PMC: 8740137. DOI: 10.3389/fmolb.2021.790613. View

11.

Smith S, Wastney M, OBrien K, Morukov B, Larina I, Abrams S . Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station. J Bone Miner Res. 2005; 20(2):208-18. DOI: 10.1359/JBMR.041105. View

12.

Schiavi J, Fodera D, Brennan M, McNamara L . Estrogen depletion alters osteogenic differentiation and matrix production by osteoblasts in vitro. Exp Cell Res. 2021; 408(1):112814. DOI: 10.1016/j.yexcr.2021.112814. View

13.

Belavy D, Baecker N, Armbrecht G, Beller G, Buehlmeier J, Frings-Meuthen P . Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest. J Bone Miner Metab. 2015; 34(3):354-65. DOI: 10.1007/s00774-015-0681-3. View

14.

Khajuria D, Disha C, Vasireddi R, Razdan R, Mahapatra D . Risedronate/zinc-hydroxyapatite based nanomedicine for osteoporosis. Mater Sci Eng C Mater Biol Appl. 2016; 63:78-87. DOI: 10.1016/j.msec.2016.02.062. View

15.

Zwart S, Rice B, Dlouhy H, Shackelford L, Heer M, Koslovsky M . Dietary acid load and bone turnover during long-duration spaceflight and bed rest. Am J Clin Nutr. 2018; 107(5):834-844. PMC: 6862931. DOI: 10.1093/ajcn/nqy029. View

16.

Dufour C, Holy X, Marie P . Skeletal unloading induces osteoblast apoptosis and targets alpha5beta1-PI3K-Bcl-2 signaling in rat bone. Exp Cell Res. 2006; 313(2):394-403. DOI: 10.1016/j.yexcr.2006.10.021. View

17.

Merrill Jr A, Hoel M, Wang E, Mullins R, Hargrove J, Jones D . Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887. FASEB J. 1990; 4(1):95-100. DOI: 10.1096/fasebj.4.1.2295381. View

18.

Chan C, Subramaniam S, Mohamed N, Muhammad N, Ramli F, Ima-Nirwana S . Circulating Biomarkers Related to Osteocyte and Calcium Homeostasis Between Postmenopausal Women with and without Osteoporosis. Endocr Metab Immune Disord Drug Targets. 2021; 21(12):2273-2280. DOI: 10.2174/1871530321666210809154456. View

19.

Han B, Wei S, Zhang X, Li H, Li Y, Li R . Effects of constrained dynamic loading, CKIP‑1 gene knockout and combination stimulations on bone loss caused by mechanical unloading. Mol Med Rep. 2018; 18(2):2506-2514. DOI: 10.3892/mmr.2018.9222. View

20.

Camacho P, Petak S, Binkley N, Diab D, Eldeiry L, Farooki A . AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE. Endocr Pract. 2020; 26(Suppl 1):1-46. DOI: 10.4158/GL-2020-0524SUPPL. View