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Review
. 2023 Aug 25;59(9):1546.
doi: 10.3390/medicina59091546.

From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease

Samradhi Singh  1 , Devojit Kumar Sarma  1 , Vinod Verma  2 , Ravinder Nagpal  3 , Manoj Kumar  1
Affiliations
Review

From Cells to Environment: Exploring the Interplay between Factors Shaping Bone Health and Disease

Samradhi Singh et al. Medicina (Kaunas). .

Abstract

The skeletal system is an extraordinary structure that serves multiple purposes within the body, including providing support, facilitating movement, and safeguarding vital organs. Moreover, it acts as a reservoir for essential minerals crucial for overall bodily function. The intricate interplay of bone cells plays a critical role in maintaining bone homeostasis, ensuring a delicate balance. However, various factors, both intrinsic and extrinsic, can disrupt this vital physiological process. These factors encompass genetics, aging, dietary and lifestyle choices, the gut microbiome, environmental toxins, and more. They can interfere with bone health through several mechanisms, such as hormonal imbalances, disruptions in bone turnover, direct toxicity to osteoblasts, increased osteoclast activity, immune system aging, impaired inflammatory responses, and disturbances in the gut-bone axis. As a consequence, these disturbances can give rise to a range of bone disorders. The regulation of bone's physiological functions involves an intricate network of continuous processes known as bone remodeling, which is influenced by various intrinsic and extrinsic factors within the organism. However, our understanding of the precise cellular and molecular mechanisms governing the complex interactions between environmental factors and the host elements that affect bone health is still in its nascent stages. In light of this, this comprehensive review aims to explore emerging evidence surrounding bone homeostasis, potential risk factors influencing it, and prospective therapeutic interventions for future management of bone-related disorders.

Keywords: aging; bone disorders; bone health; bone remodeling; gut microbiome; gut-bone axis; osteoporosis; probiotics; regenerative therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
This diagram illustrates the vital roles of RANKL/RANK, Jagged1/Notch1, and Wnt/β-catenin pathways in preserving bone health, maintaining bone homeostasis, and regulating bone mineral density (BMD). Although each pathway operates autonomously, they intricately interact to collectively oversee the multifaceted process of bone remodeling. By interconnecting, these pathways ensure the perpetual renewal and durability of bone tissue.
Figure 2
Figure 2
Diagram shows the putative mechanism by which intrinsic and extrinsic variables impact bone health. TNF: Tumor Necrosis Factor; IL: Interleukin; RANKL: receptor activator of NF-kB ligand; OPG: Osteoprotegerin.
Figure 3
Figure 3
An illustration of the gut–bone axis that highlights the causes and processes starting with gut dysbiosis, leading to dysregulation in the bone homeostasis mechanism that favors osteoclasts boosting bone resorption and encouraging the emergence of bone diseases. LPS: Lipolysaccharide; ILs: Interleukins; SCFAs: Short chain fatty acids; RANKL: Receptor activator of NF-kB ligand; OPG: Osteoprotegerin; PM: Particulate Matter; EDCs Endocrine Disrupting Chemicals.
Figure 4
Figure 4
Diagram illustrates the putative mode of action of the potential therapeutic interventions that could be used for promoting bone health and treating bone disorders. IL: Interleukin; miRNA: microRNA; MSC: Mesenchymal Stem Cells.
See this image and copyright information in PMC

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References

    1. Lorincz C., Manske S.L., Zernicke R. Bone Health: Part 1, Nutrition. Sports Health A Multidiscip. Approach. 2009;1:253–260. doi: 10.1177/1941738109334213. - DOI - PMC - PubMed
    1. Föger-Samwald U., Dovjak P., Azizi-Semrad U., Kerschan-Schindl K., Pietschmann P. Osteoporosis: Pathophysiology and therapeutic options. EXCLI J. 2020;19:1017–1037. - PMC - PubMed
    1. Bhardwaj A., Sapra L., Tiwari A., Mishra P.K., Sharma S., Srivastava R.K. “Osteomicrobiology”: The Nexus Between Bone and Bugs. Front. Microbiol. 2022;12:812466. doi: 10.3389/fmicb.2021.812466. - DOI - PMC - PubMed
    1. Wu A.M., Bisignano C., James S.L., Abady G.G., Abedi A., Abu-Gharbieh E., Alhassan R.K., Alipour V., Arabloo J., Asaad M., et al. Global, regional, and national burden of bone fractures in 204 countries and territories, 1990–2019: A systematic analysis from the Global Burden of Disease Study 2019. Lancet Healthy Longev. 2021;2:e580–e592. doi: 10.1016/S2666-7568(21)00172-0. - DOI - PMC - PubMed
    1. Sozen T., Ozisik L., Basaran N.C. An overview and management of osteoporosis. Eur. J. Rheumatol. 2017;4:46–56. doi: 10.5152/eurjrheum.2016.048. - DOI - PMC - PubMed

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This research received no external funding.