Effect of magnesium deficiency on bone health

Authors

  • Ninel Diedukh SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine https://orcid.org/0000-0003-0307-2328
  • Nataliia Grygorieva SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine https://orcid.org/0000-0002-4266-461X
  • Anna Musiienko SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv, Ukraine

DOI:

https://doi.org/10.15674/0030-598720234121-127

Keywords:

Magnesium-dependent bone disorders, osteoporosis, fractures, bone regeneration

Abstract

Objective. To assess the impact of magnesium deficiency on bone metabolism based on an analytical analysis of current literature, as well as to systematize data on the impact of magnesium deficiency on the development of osteoporosis, bone regeneration, and to consider it as a risk factor for fracture. Methods. The review is based on the analysis of literature sources from PubMed, Scopus, Web of Science, Cochrane Library, Google, Google Scholar, and RLNS. The search was conducted by keywords: magnesium, deficiency, magnesium and bone tissue, magnesium and osteoporosis, magnesium and fractures, magnesium and bone regeneration. Results. Magnesium is a key element in the metabolic and regulatory processes of the body. Its effects on bone tissue are direct and indirect. The direct magnesium effect on genes involved in osteogenesis is accompanied by proliferation of mesenchymal stem cells and osteoblasts, but magnesium deficiency leads to their reduction and apoptosis. In case of magnesium deficiency, the number and activity of osteoclasts increases. Magnesium regulates bone mineralization in a concentration-dependent manner. Magnesium deficiency increases bone resorption and affects osteopenia and osteoporosis, which can occur indirectly through decreased vitamin D levels, increased biosynthesis of parathyroid hormone, increased oxidative stress and biosynthesis of proinflammatory cytokines. However, data on bone mineral density at different skeletal sites in magnesium deficiency are ambiguous. Magnesium deficiency is considered a risk factor for fracture. It is of great importance for bone regeneration, affecting in various ways: it stimulates the proliferation and differentiation of mesenchymal stem cells and osteoblasts, periosteum cells, increases the movement of osteoblasts to the area of traumatic bone injury, and activates signaling pathways. At the early stage of regeneration magnesium has a positive effect on macrophages, its specificity of action is inhibition of transformation of M2 macrophages into M1 at the tissue-specific stage of regeneration. One of the mechanisms stimulating regeneration may be the effect of magnesium on axons, release and increase of calcitonin-related polypeptide α. Conclusions. Since hypomagnesemia is a potentially modifiable factor, this opens up prospects for maintaining bone health and requires further research in this area.

Author Biographies

Ninel Diedukh, SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv

Doctor in Biol. Sci., Prof.

Nataliia Grygorieva, SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv

MD, Prof. in Traumatology and Orthopaedics

Anna Musiienko, SI «D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine», Kyiv

PhD

References

  1. DiNicolantonio, J. J., O'Keefe, J. H., & Wilson, W. (2018). Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open heart, 5 (1), e000668. https://doi.org/10.1136/openhrt-2017-000668
  2. Rosique-Esteban, N., Guasch-Ferré, M., Hernández-Alonso, P., & Salas-Salvado, J. (2018). Dietary Magnesium and Cardiovascular Disease: A Review with Emphasis in Epidemiological Studies. Nutrients, 10 (2), 168. https://doi.org/10.3390/nu10020168
  3. Choi, S., Kim, K. J., Cheon, S., Kim, E. M., Kim, Y. A., Park, C., & Kim, K. K. (2020). Biochemical activity of magnesium ions on human osteoblast migration. Biochemical and biophysical research communications, 531 (4), 588–594. https://doi.org/10.1016/j.bbrc.2020.07.057
  4. Fiorentini, D., Cappadone, C., Farruggia, G., & Prata, C. (2021). Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Nutrients, 13 (4), 1136. https://doi.org/10.3390/nu13041136
  5. Qi, T., Weng, J., Yu, F., Zhang, W., Li, G., Qin, H., Tan, Z., & Zeng, H. (2021). Insights into the Role of Magnesium Ions in Affecting Osteogenic Differentiation of Mesenchymal Stem Cells. Biological trace element research, 199 (2), 559–567. https://doi.org/10.1007/s12011-020-02183-y
  6. Erem, S., Atfi, A., & Razzaque, M. S. (2019). Anabolic effects of vitamin D and magnesium in aging bone. The Journal of steroid biochemistry and molecular biology, 193, 105400. https://doi.org/10.1016/j.jsbmb.2019.105400
  7. Jahnen-Dechent, W., & Ketteler, M. (2012). Magnesium basics. Clinical kidney journal, 5 (Suppl 1), i3–i14. https://doi.org/10.1093/ndtplus/sfr163
  8. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (1997). Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. 6 Magnesium. Washington (DC): National Academies Press (US). Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK109816.
  9. de Baaij, J. H., Hoenderop, J. G., & Bindels, R. J. (2015). Magnesium in man: implications for health and disease. Physiological reviews, 95 (1), 1–46. https://doi.org/10.1152/physrev.00012.2014
  10. Ismail, A. A. A., Ismail, Y., & Ismail, A. A. (2018). Chronic magnesium deficiency and human disease; time for reappraisal? QJM: monthly journal of the Association of Physicians, 111 (11), 759–763. https://doi.org/10.1093/qjmed/hcx186
  11. Shahsavani, Z., Asadi, A. H., Shamshirgardi, E., & Akbarzadeh, M. (2021). Vitamin D, Magnesium and Their Interactions: A Review. International Journal of Nutrition Sciences, 6(3), 113–118. https://doi.org/10.30476/IJNS.2021.91766.1144
  12. Uwitonze, A. M., & Razzaque, M. S. (2018). Role of Magnesium in Vitamin D Activation and Function. The Journal of the American Osteopathic Association, 118 (3), 181–189. https://doi.org/10.7556/jaoa.2018.037
  13. Reddy, P., & Edwards, L. R. (2019). Magnesium Supplementation in Vitamin D Deficiency. American journal of therapeutics, 26 (1), e124–e132. https://doi.org/10.1097/MJT.0000000000000538
  14. Uwitonze, A. M., Rahman, S., Ojeh, N., Grant, W. B., Kaur, H., Haq, A., & Razzaque, M. S. (2020). Oral manifestations of magnesium and vitamin D inadequacy. The Journal of steroid biochemistry and molecular biology, 200, 105636. https://doi.org/10.1016/j.jsbmb.2020.105636
  15. Razzaque M. S. (2018). Magnesium: Are We Consuming Enough? Nutrients, 10 (12), 1863. https://doi.org/10.3390/nu10121863
  16. Akizawa, Y., Koizumi, S., Itokawa, Y., Ojima, T., Nakamura, Y., Tamura, T., & Kusaka, Y. (2008). Daily magnesium intake and serum magnesium concentration among Japanese people. Journal of epidemiology, 18 (4), 151–159. https://doi.org/10.2188/jea.je2007381
  17. Kim, J. M., Yang, Y. S., Hong, J., Chaugule, S., Chun, H., van der Meulen, M. C. H., Xu, R., Greenblatt, M. B., & Shim,J. H. (2022). Biphasic regulation of osteoblast development via the ERK MAPK-mTOR pathway. ЕLife, 11, e78069. https://doi.org/10.7554/eLife.78069
  18. Diaz-Tocados, J. M., Herencia, C., Martinez-Moreno, J. M., Montes de Oca, A., Rodriguez-Ortiz, M. E., Vergara, N., Blanco, A., Steppan, S., Almaden, Y., Rodriguez, M., & Munoz-Castaneda, J. R. (2017). Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells. Scientific reports, 7 (1), 7839. https://doi.org/10.1038/s41598-017-08379-y
  19. Wu, L., Feyerabend, F., Schilling, A. F., Willumeit-Romer,R., & Luthringer, B. J. C. (2015). Effects of extracellular magnesium extract on the proliferation and differentiation of human osteoblasts and osteoclasts in coculture. Acta biomaterialia, 27, 294–304. https://doi.org/10.1016/j.actbio.2015.08.042
  20. Li, Y., Wang, J., Yue, J., Wang, Y., Yang, C., & Cui, Q. (2018). High magnesium prevents matrix vesicle-mediated mineralization in human bone marrow-derived mesenchymal stem cells via mitochondrial pathway and autophagy. Cell biology international, 42 (2), 205–215. https://doi.org/10.1002/cbin.10888
  21. Zhang, J., Tang, L., Qi, H., Zhao, Q., Liu, Y., & Zhang, Y. (2019). Dual Function of Magnesium in Bone Biomineralization. Advanced healthcare materials, 8 (21), e1901030. https://doi.org/10.1002/adhm.201901030
  22. Castiglioni, S., Cazzaniga, A., Albisetti, W., & Maier, J. A. (2013). Magnesium and osteoporosis: current state of knowledge and future research directions. Nutrients, 5 (8), 3022–3033. https://doi.org/10.3390/nu5083022
  23. Al Alawi, A. M., Majoni, S. W., & Falhammar, H. (2018). Magnesium and Human Health: Perspectives and Research Directions. International journal of ndocrinology, 2018, 9041694. https://doi.org/10.1155/2018/9041694
  24. Dominguez, L. J., Veronese, N., Ciriminna, S., Perez-Albela, J. L., Vasquez-López, V. F., Rodas-Regalado, S., Di Bella, G., Parisi, A., Tagliaferri, F., & Barbagallo, M. (2023). Association between Serum Magnesium and Fractures: A Systematic Review and Meta-Analysis of Observational Studies. Nutrients, 15 (6), 1304. https://doi.org/10.3390/nu15061304
  25. Zhou, H., Liang, B., Jiang , H., Denga, Z., & Yu, K. (2021). Magnesium-based biomaterials as emerging agents for bone repair and regeneration: from mechanism to application. Journal of Magnesium and Alloys, 9, 779–804. https://doi.org/10.1016/j.jma.2021.03.004
  26. Chang, J., Yu, D., Ji, J., Wang, N., Yu, S., & Yu, B. (2020). The Association Between the Concentration of Serum Magnesium and Postmenopausal Osteoporosis. Frontiers in medicine, 7, 381. https://doi.org/10.3389/fmed.2020.00381
  27. Mederle, O. A., Balas, M., Ioanoviciu, S. D., Gurban, C. V., Tudor, A., & Borza, C. (2018). Correlations between bone turnover markers, serum magnesium and bone mass density in postmenopausal osteoporosis. Clinical interventions in aging, 13, 1383–1389. https://doi.org/10.2147/CIA.S170111
  28. Orchard, T. S., Larson, J. C., Alghothani, N., Bout-Tabaku, S., Cauley, J. A., Chen, Z., LaCroix, A. Z., Wactawski-Wende,J., & Jackson, R. D. (2014). Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study. The American journal of clinical nutrition, 99 (4), 926–933. https://doi.org/10.3945/ajcn.113.067488
  29. Groenendijk, I., van Delft, M., Versloot, P., van Loon, L.J. C., & de Groot, L. C. P. G. M. (2022). Impact of magnesium on bone health in old er adults: A systematic review and meta-analysis. Bone, 154, 116233. https://doi.org/10.1016/j.bone.2021.116233
  30. Farsinejad-Marj, M., Saneei, P., & Esmaillzadeh, A. (2016). Dietary magnesium intake, bone mineral density and risk of fracture: a systematic review and meta-analysis. Osteoporosis International. 27 (4), 1389–1399. https://doi.org/10.1007/s00198-015-3400-y
  31. Wright, H. H., Kruger, M. C., Schutte, W. D., Wentzel-Viljoen,E., Kruger, I. M., & Kruger, H. S. (2019). Magnesium Intake Predicts Bone Turnover in Postmenopausal Black South African Women. Nutrients, 11 (10), 2519. https://doi.org/10.3390/nu11102519
  32. Kunutsor, S. K., Whitehouse, M. R., Blom, A. W., & Laukkanen,J. A. (2017). Low serum magnesium levels are associated with increased risk of fractures: a long-term prospective cohort study. European journal of epidemiology, 32 (7), 593–603. https://doi.org/10.1007/s10654-017-0242-2
  33. Veronese, N., Stubbs, B., Solmi, M., Noale, M., Vaona, A., Demurtas, J., & Maggi, S. (2017). Dietary magnesium intake and fracture risk: data from a large prospective study. The British journal of nutrition, 117 (11), 1570–1576. https://doi.org/10.1017/S0007114517001350
  34. Rondanelli, M., Faliva, M. A., Tartara, A., Gasparri, C., Perna, S., Infantino, V., Riva, A., Petrangolini, G., & Peroni, G. (2021). An update on magnesium and bone health. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 34 (4), 715–736. https://doi.org/10.1007/s10534-021-00305-0
  35. Antoniac, I., Miculescu, M., Mănescu Păltânea, V., Stere, A., Quan, P. H., Păltânea, G., Robu, A., & Earar, K. (2022). Magnesium-Based Alloys Used in Orthopedic Surgery. Materials (Basel, Switzerland), 15 (3), 1148. https://doi.org/10.3390/ma15031148
  36. Chow, D. H. K., Wang, J., Wan, P., Zheng, L., Ong, M. T. Y., Huang, L., Tong, W., Tan, L., Yang, K., & Qin, L. (2021). Biodegradable magnesium pins enhanced the healing of transverse patellar fracture in rabbits. Bioactive materials, 6 (11), 4176–4185. https://doi.org/10.1016/j.bioactmat.2021.03.044
  37. Hung, C. C., Chaya, A., Liu, K., Verdelis, K., & Sfeir, C. (2019). The role of magnesium ions in bone regeneration involves the canonical Wnt signaling pathway. Acta biomaterialia, 98, 246–255. https://doi.org/10.1016/j.actbio.2019.06.001
  38. Libako, P., Nowacki, W., Castiglioni, S., Mazur, A., & Maier,J. A. (2016). Extracellular magnesium and calcium blockers modulate macrophage activity. Magnesium research, 29 (1), 11–21. https://doi.org/10.1684/mrh.2016.0398
  39. Wang, G., Luo, J., Qiao, Y., Zhang, D., Liu, Y., Zhang, W., Liu, X.,& Jiang, X. (2022). AMPK/mTOR Pathway Is Involved in Autophagy Induced by Magnesium-Incorporated TiO2 Surface to Promote BMSC Osteogenic Differentiation. Journal of functional biomaterials, 13 (4), 221. https://doi.org/10.3390/jfb13040221
  40. Zhang, Y., Xu, J., Ruan, Y. C., Yu, M. K., O'Laughlin, M., Wise, H., Chen, D., Tian, L., Shi, D., Wang, J., Chen, S., Feng, J. Q., Chow, D. H., Xie, X., Zheng, L., Huang, L.,
  41. Huang, S., Leung, K., Lu, N., Zhao, L., … Qin, L. (2016). Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nature medicine, 22 (10), 1160–1169. https://doi.org/10.1038/nm.4162
  42. Xie, H., Cui, Z., Wang, L., Xia, Z., Hu, Y., Xian, L., Li, C., Xie, L., Crane, J., Wan, M., Zhen, G., Bian, Q., Yu, B., Chang,W., Qiu, T., Pickarski, M., Duong, L. T., Windle, J. J., Luo, X., Liao, E., … Cao, X. (2014). PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nature medicine, 20 (11), 1270–1278. https://doi.org/10.1038/nm.3668
  43. Peng, Y., Wu, S., Li, Y., & Crane, J. L. (2020). Type H blood vessels in bone modeling and remodeling. Theranostics, 10 (1), 426–436. https://doi.org/10.7150/thno.34126
  44. Lin, S., Yang, G., Jiang, F., Zhou, M., Yin, S., Tang, Y., Tang, T., Zhang, Z., Zhang, W., & Jiang, X. (2019). A Magnesium-Enriched 3D Culture System that Mimics the Bone Development Microenvironment for Vascularized Bone Regeneration. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 6 (12), 1900209. https://doi.org/10.1002/advs.201900209
  45. Belluci, M. M., Giro, G., Del Barrio, R. A. L., Pereira, R. M. R., Marcantonio, E., Jr, & Orrico, S. R. P. (2011). Effects ofmagnesium intake deficiency on bone metabolism and bone tissue around osseointegrated implants. Clinical oral implants research, 22 (7), 716–721. https://doi.org/10.1111/j.1600-0501.2010.02046.x
  46. Song, Y., Xu, L., Jin, X., Chen, D., Jin, X., & Xu, G. (2022). Effect of calcium and magnesium on inflammatory cytokines in accidentally multiple fracture adults: A short-term follow-up. Medicine, 101 (1), e28538. https://doi.org/10.1097/MD.0000000000028538
  47. Veronese, N., Pizzol, D., Smith, L., Dominguez, L. J., & Barbagallo,M. (2022). Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials. Nutrients, 14 (3), 679. https://doi.org/10.3390/nu14030679

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Diedukh, N. ., Grygorieva, N. ., & Musiienko, A. . (2024). Effect of magnesium deficiency on bone health. ORTHOPAEDICS TRAUMATOLOGY and PROSTHETICS, (4), 121–127. https://doi.org/10.15674/0030-598720234121-127

Issue

No. 4 (2023)

Section

DIGESTS AND REVIEWS

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