Investigating the effect of zinc supplementation on preventing bone resorption in a weightlessness animal model: An experimental study

Eslami, Reza; Khoshvaghti, Amir; Alizadeh, Kamyab

doi:10.22034/26.4.89

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Volume 26, Issue 4 (Winter 2024)

EBNESINA 2024, 26(4): 89-96

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Investigating the effect of zinc supplementation on preventing bone resorption in a weightlessness animal model: An experimental study

Reza Eslami

, Amir Khoshvaghti

, Kamyab Alizadeh ^*

School of Aerospace and Subaquatic Medicine, Aja University of Medical Sciences, Tehran, Iran , Kamyab_alizadeh@yahoo.com

Keywords: Microgravity Simulation, Tail Suspension, Osteocalcin, Alkaline Phosphatase, Zinc Sulfate

Full-Text [PDF 1396 kb] (180 Downloads) | Abstract (HTML) (581 Views)

Type of Study: Brief Report | Subject: Aerospace Medicine
Received: 2024/11/21 | Revised: 2025/03/12 | Accepted: 2024/12/16 | Published: 2024/12/21

Extended Abstract: (223 Views)

Introduction

Research indicates that weightlessness in space can lead to bone and muscle atrophy, potentially resulting in conditions like osteoporosis and other musculoskeletal disorders [4]. A study involving four cosmonauts who spent up to seven months aboard the Russian space station demonstrated that bone density loss in the legs, particularly in cortical bone, occurred at a rate of approximately 0.3–0.4% per month, primarily affecting trabecular bone mass [7]. Further research using animal models of differing durations of simulated spaceflight has revealed changes in both cortical and trabecular bone, with a transient increase in bone resorption and a sustained decrease in bone formation. However, limited information exists regarding interventions that can stabilize bone metabolism and prevent bone loss during space missions. Previous attempts to administer high doses of calcium and vitamin D supplements during spaceflight have not effectively prevented osteoporosis, as these interventions failed to inhibit bone resorption, despite maintaining serum calcium levels [8].
Zinc is a vital element with several physiological roles, particularly concerning bone growth and metabolism. It stimulates osteoblast cell differentiation, proliferation, and mineralization, promoting bone production. Zinc enhances the production of bone growth factors and matrix proteins essential for bone formation. The enzyme DNA polymerase, important for DNA replication, is zinc-dependent, suggesting that zinc may promote DNA synthesis in osteoblasts of bone tissue [9].
Bone biomarkers play a crucial role in both research and monitoring therapeutic interventions with regards to bone health. These markers represent products—such as bone-specific alkaline phosphatase (BAP) and osteocalcin—expressed by activated osteoblasts at various stages of maturation. BAP serves as a key marker of bone formation; it is a hydrolase enzyme associated with cell membranes, responsible for hydrolyzing phosphate groups from a variety of molecules, including nucleotides, proteins, and alkaloids. Osteocalcin is a non-collagenous protein produced by osteoblasts, playing a critical role in bone mineralization and the maintenance of calcium homeostasis. Serum osteocalcin levels reflect bone formation and the presence of osteoblasts, acting as biomarkers for bone formation. Importantly, osteocalcin is one of the few proteins unique to the skeletal system [10].
Given the significant costs associated with space travel, researchers have attempted to artificially induce weightlessness on Earth. Among these techniques, tail suspension of mice is widely used as a laboratory simulation of space travel. This method mimics the effects of weightlessness on the bones and muscles of the animal's hind legs, allowing for the replication of blood flow patterns experienced by humans in weightlessness [11]. Given that changes in bone structure are a major concern during spaceflight, this study aimed to investigate alterations in bone biomarkers with and without zinc sulfate supplementation in an experimental model simulating spaceflight.

Methods

In this experimental study, 14 male mice weighing an average of 250 g were randomly divided into two groups: an intervention group and a control group. Initially, all mice were housed together for one week under controlled conditions (temperature: 23 ± 2 °C, humidity: 60 ± 10%, and a 12-hour light/dark cycle) while being fed the same diet. Following this acclimatization phase, each group was placed separately in cages specifically designed to simulate weightlessness [11]. For hindlimb suspension, the mice were positioned at a 30-degree angle to the cage floor to ensure that their hind legs did not touch the grid floor of the cage. Over 30 days, both groups received their usual diet, while the intervention group additionally recived zinc sulfate (227 mg/L). Blood samples were collected at the beginning and end of the study to analyze changes in bone biomarkers.

Results

During the 30-day period, there was a significant increase in BAP levels in both groups (p<0.001). Notably, the increase in BAP observed in the intervention group was significantly greater than that in the control group (p<0.001). In terms of osteocalcin levels, a significant decrease was noted in both groups over the 30-day period (p<0.05). However, there was no significant difference in this variable between the two groups after the study period.

Discussion and Conclusion

This study investigated the effects of oral zinc supplementation and weightlessness on specific bone formation markers (BAP and osteocalcin) over a 30-day duration using a simulated model. The results showed that weightlessness significantly decreased osteocalcin levels in suspended mice. Although 30 days of oral zinc supplementation did not improve osteocalcin levels, it significantly increased BAP levels compared to the control group.
Based on the findings of this investigation, while BAP levels may initially show an increase (indicating some osteoblastic activity), osteocalcin typically decreases due to an overall reduction in bone formation. The efficacy of zinc supplementation in enhancing alkaline phosphatase activity has been previously established. Seo et al. demonstrated that zinc can amplify osteogenic effects by stimulating cell proliferation, alkaline phosphatase activity, and collagen synthesis in osteoblast cells [14]. Lowe et al. highlighted zinc as a critical component in alkaline phosphatase synthesis and emphasized its importance for enzyme activity [15]. Additionally, Park et al. found that zinc inhibits osteoclastogenesis by interfering with the Ca2+-Calcineurin-NFATc1 signaling pathway in bone marrow-derived monocytes, suggesting its potential as a treatment for osteoporosis [16]. Numerous studies have indicated that dietary zinc supplementation effectively prevents bone resorption. Chou et al. observed that zinc supplementation was beneficial in the prevention and treatment of osteoporosis in mouse models [17]. Sun et al. illustrated the effectiveness of dietary zinc on bone growth, metabolism, and the expression of IGF-I and alkaline phosphatase genes in growing male mice [18].
The results of this study indicated that weightlessness significantly reduced osteocalcin levels (a marker of bone formation) regardless of zinc supplementation. While dietary zinc significantly increased BAP levels, it did not prevent the reduction in osteocalcin due to weightlessness. These findings suggest that zinc supplementation may not effectively counteract bone loss during long-term spaceflight, highlighting the need for further research to develop optimal strategies for maintaining bone health in weightless environments.

Ethical Considerations

In the present study, approved by Aja University of Medical Sciences (code: 92108), all care and ethical principles were fully observed in accordance with international guidelines for the care and use of laboratory animals.

Funding

This study was conducted with the financial support of Aja University of Medical Sciences.

Authors’ Contribution

Authors contributed equally to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.

Conflict of Interest

Authors declared no conflict of interest.

Acknowledgments

The authors would like to thank the cooperation of Iran University of Medical Sciences and the School of Aerospace and Subaquatic Medicine, Aja University of Medical Sciences.

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Eslami R, Khoshvaghti A, Alizadeh K. Investigating the effect of zinc supplementation on preventing bone resorption in a weightlessness animal model: An experimental study. EBNESINA 2024; 26 (4) :89-96
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