骨质疏松症与慢性砷暴露关系研究进展
Research Progress on the Relationship between Osteoporosis and Chronic Arsenic Exposure
DOI: 10.12677/bp.2025.154033, PDF,   
作者: 邓翰林：重庆医科大学公共卫生学院，重庆
关键词: 砷；骨质流失；骨质疏松症；Arsenic； Bone Loss； Osteoporosis
摘要: 骨质疏松症是一种代谢性骨病，多见于老年人群中，其最主要的结局是多发性骨折的出现。骨质疏松症的发病机制目前尚未完全明确，但普遍认为其具有复杂的病因网络，越来越多的证据表明慢性砷暴露在骨质疏松症发生发展的病因网络中占据重要地位。慢性砷暴露具有对骨组织直接和间接损害的能力，也可能通过与其他高危因素的相互作用来加重骨质疏松症的发生风险。探明砷暴露的作用机制，将其纳入早期监测指标和行为干预计划，将对骨质疏松症的防治具有很大的积极作用。本研究通过查阅国内外文献，综述了目前慢性砷暴露在骨质流失与骨质疏松症发生发展中的作用，为未来制定骨质疏松症的新防治策略提供依据。
Abstract: Osteoporosis is a metabolic bone disease commonly seen in the elderly, with its most significant outcome being the occurrence of multiple fractures. The pathogenesis of osteoporosis is not yet fully understood, but it is generally believed to involve a complex network of causative factors. Increasing evidence suggests that chronic arsenic exposure plays a significant role in the etiology and progression of osteoporosis. Chronic arsenic exposure has the capacity to cause direct and indirect damage to bone tissue and may also exacerbate the risk of osteoporosis through interactions with other high-risk factors. Investigating the mechanisms of arsenic exposure and incorporating it into early monitoring indicators and behavioral intervention plans will have a highly positive impact on the prevention and treatment of osteoporosis. This study reviews domestic and international literature to summarize the role of chronic arsenic exposure in bone loss and the development of osteoporosis, providing a basis for formulating new prevention and treatment strategies for osteoporosis in the future.
文章引用：邓翰林. 骨质疏松症与慢性砷暴露关系研究进展[J]. 生物过程, 2025, 15(4): 257-264. https://doi.org/10.12677/bp.2025.154033

参考文献

[1] Compston, J.E., McClung, M.R. and Leslie, W.D. (2019) Osteoporosis. The Lancet, 393, 364-376. [Google Scholar] [CrossRef] [PubMed]
[2] Yedavally-Yellayi, S., Ho, A.M. and Patalinghug, E.M. (2019) Update on Osteoporosis. Primary Care: Clinics in Office Practice, 46, 175-190. [Google Scholar] [CrossRef] [PubMed]
[3] Sözen, T., Özışık, L. and Çalık Başaran, N. (2019) An Overview and Management of Osteoporosis. European Journal of Rheumatology, 4, 46-56. [Google Scholar] [CrossRef] [PubMed]
[4] Cosman, F., de Beur, S.J., LeBoff, M.S., Lewiecki, E.M., Tanner, B., Randall, S., et al. (2014) Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporosis International, 25, 2359-2381. [Google Scholar] [CrossRef] [PubMed]
[5] Hoong, C.W.S., Saul, D., Khosla, S. and Sfeir, J.G. (2025) Advances in the Management of Osteoporosis. BMJ, 390, e081250. [Google Scholar] [CrossRef] [PubMed]
[6] Kobayashi, S., Takahashi, H.E., Ito, A., Saito, N., Nawata, M., Horiuchi, H., et al. (2003) Trabecular Minimodeling in Human Iliac Bone. Bone, 32, 163-169. [Google Scholar] [CrossRef] [PubMed]
[7] Blair, H.C., Larrouture, Q.C., Li, Y., Lin, H., Beer-Stoltz, D., Liu, L., et al. (2017) Osteoblast Differentiation and Bone Matrix Formation in Vivo and in Vitro. Tissue Engineering Part B: Reviews, 23, 268-280. [Google Scholar] [CrossRef] [PubMed]
[8] Clarke, B. (2008) Normal Bone Anatomy and Physiology. Clinical Journal of the American Society of Nephrology, 3, S131-S139. [Google Scholar] [CrossRef] [PubMed]
[9] Buckwalter, J.A., Glimcher, M.J., Cooper, R.R., et al. (1996) Bone Biology. I: Structure, Blood Supply, Cells, Matrix, and Mineralization. Instructional Course Lectures, 45, 371-386.
[10] Oremland, R.S. and Stolz, J.F. (2003) The Ecology of Arsenic. Science, 300, 939-944. [Google Scholar] [CrossRef] [PubMed]
[11] 窦殿程, 齐嵘, 肖淑敏, 等. 中国饮用水中砷的分布特征及基于伤残调整寿命年的健康风险评价[J]. 环境科学, 2024, 45(1): 131-139.
[12] Su, Q., He, Y., Pan, H., Liu, H., Mehmood, K., Tang, Z., et al. (2023) Toxicity of Inorganic Arsenic to Animals and Its Treatment Strategies. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 271, Article ID: 109654. [Google Scholar] [CrossRef] [PubMed]
[13] Ratnaike, R.N. (2003) Acute and Chronic Arsenic Toxicity. Postgraduate Medical Journal, 79, 391-396. [Google Scholar] [CrossRef] [PubMed]
[14] Rodríguez, J. and Mandalunis, P.M. (2018) A Review of Metal Exposure and Its Effects on Bone Health. Journal of Toxicology, 2018, Article ID: 4854152. [Google Scholar] [CrossRef] [PubMed]
[15] Melis, S., Trompet, D., Chagin, A.S. and Maes, C. (2024) Skeletal Stem and Progenitor Cells in Bone Physiology, Ageing and Disease. Nature Reviews Endocrinology, 21, 135-153. [Google Scholar] [CrossRef] [PubMed]
[16] Hu, Y., Cheng, H., Hsieh, B., Huang, L., Huang, T. and Chang, K. (2012) Arsenic Trioxide Affects Bone Remodeling by Effects on Osteoblast Differentiation and Function. Bone, 50, 1406-1415. [Google Scholar] [CrossRef] [PubMed]
[17] Kobayashi, T. and Kronenberg, H. (2005) Minireview: Transcriptional Regulation in Development of Bone. Endocrinology, 146, 1012-1017. [Google Scholar] [CrossRef] [PubMed]
[18] Hinoi, E., Fujimori, S., Wang, L., Hojo, H., Uno, K. and Yoneda, Y. (2006) Nrf2 Negatively Regulates Osteoblast Differentiation via Interfering with Runx2-Dependent Transcriptional Activation. Journal of Biological Chemistry, 281, 18015-18024. [Google Scholar] [CrossRef] [PubMed]
[19] Wu, C., Lu, T., Chan, D., Tsai, K., Yang, R. and Liu, S. (2014) Effects of Arsenic on Osteoblast Differentiation in Vitro and on Bone Mineral Density and Microstructure in Rats. Environmental Health Perspectives, 122, 559-565. [Google Scholar] [CrossRef] [PubMed]
[20] Abbas, S., Khan, K., Khan, M.P., Nagar, G.K., Tewari, D., Maurya, S.K., et al. (2013) Developmental Exposure to As, Cd, and Pb Mixture Diminishes Skeletal Growth and Causes Osteopenia at Maturity via Osteoblast and Chondrocyte Malfunctioning in Female Rats. Toxicological Sciences, 134, 207-220. [Google Scholar] [CrossRef] [PubMed]
[21] Nojiri, H., Saita, Y., Morikawa, D., Kobayashi, K., Tsuda, C., Miyazaki, T., et al. (2011) Cytoplasmic Superoxide Causes Bone Fragility Owing to Low-Turnover Osteoporosis and Impaired Collagen Cross-Linking. Journal of Bone and Mineral Research, 26, 2682-2694. [Google Scholar] [CrossRef] [PubMed]
[22] Tang, C., Chiu, Y., Huang, C., Chen, Y. and Chen, P. (2009) Arsenic Induces Cell Apoptosis in Cultured Osteoblasts through Endoplasmic Reticulum Stress. Toxicology and Applied Pharmacology, 241, 173-181. [Google Scholar] [CrossRef] [PubMed]
[23] Mondal, V., Hosen, Z., Hossen, F., Siddique, A.E., Tony, S.R., Islam, Z., et al. (2020) Arsenic Exposure-Related Hyperglycemia Is Linked to Insulin Resistance with Concomitant Reduction of Skeletal Muscle Mass. Environment International, 143, Article ID: 105890. [Google Scholar] [CrossRef] [PubMed]
[24] Zhang, Y., Xing, H., Hu, Z., Xu, W., Tang, Y., Zhang, J., et al. (2023) Independent and Combined Associations of Urinary Arsenic Exposure and Serum Sex Steroid Hormones among 6-19-Year Old Children and Adolescents in NHANES 2013-2016. Science of The Total Environment, 863, Article ID: 160883. [Google Scholar] [CrossRef] [PubMed]
[25] Kousteni, S., Chen, J.-.R, Bellido, T., Han, L., Ali, A.A., O’Brien, C.A., et al. (2002) Reversal of Bone Loss in Mice by Nongenotropic Signaling of Sex Steroids. Science, 298, 843-846. [Google Scholar] [CrossRef] [PubMed]
[26] Teitelbaum, S.L. and Ross, F.P. (2003) Genetic Regulation of Osteoclast Development and Function. Nature Reviews Genetics, 4, 638-649. [Google Scholar] [CrossRef] [PubMed]
[27] Boyle, W.J., Simonet, W.S. and Lacey, D.L. (2003) Osteoclast Differentiation and Activation. Nature, 423, 337-342. [Google Scholar] [CrossRef] [PubMed]
[28] Lever, J.H. (2002) Paget’s Disease of Bone in Lancashire and Arsenic Pesticide in Cotton Mill Wastewater: A Speculative Hypothesis. Bone, 31, 434-436. [Google Scholar] [CrossRef] [PubMed]
[29] Hasebe, M. and Hamasaki, A. (2025) Paget’s Disease of Bone. New England Journal of Medicine, 392, 1953-1953. [Google Scholar] [CrossRef] [PubMed]
[30] 李浩, 覃子秀, 王冰洁, 等. 骨保护素、核因子-κB受体活化因子配基在氟砷联合染毒大鼠骨骼毒性中的调控作用[J]. 中华地方病学杂志, 2018, 37(6): 461-466.
[31] Nie, C., Hu, J., Wang, B., Li, H., Yang, X. and Hong, F. (2022) Effects of Co-Exposure to Fluoride and Arsenic on TRAF-6 Signaling and NF-κB Pathway of Bone Metabolism. Biological Trace Element Research, 201, 4447-4455. [Google Scholar] [CrossRef] [PubMed]
[32] Szymczyk, K.H., Kerr, B.A.E., Freeman, T.A., Adams, C.S. and Steinbeck, M.J. (2006) Involvement of Hydrogen Peroxide in the Differentiation and Apoptosis of Preosteoclastic Cells Exposed to Arsenite. Biochemical Pharmacology, 72, 761-769. [Google Scholar] [CrossRef] [PubMed]
[33] Liu, Z., Hou, Y., Li, L., Yang, Y., Jia, J., Hong, Z., et al. (2019) Nrf2 Deficiency Aggravates the Increase in Osteoclastogenesis and Bone Loss Induced by Inorganic Arsenic. Toxicology and Applied Pharmacology, 367, 62-70. [Google Scholar] [CrossRef] [PubMed]
[34] Aybar Odstrcil, A.d.C., Carino, S.N., Diaz Ricci, J.C. and Mandalunis, P.M. (2010) Effect of Arsenic in Endochondral Ossification of Experimental Animals. Experimental and Toxicologic Pathology, 62, 243-249. [Google Scholar] [CrossRef] [PubMed]
[35] Lindgren, A., Vahter, M. and Dencker, L. (1982) Autoradiographic Studies on the Distribution of Arsenic in Mice and Hamsters Administered 74As‐Arsenite or ‐Arsenate. Acta Pharmacologica et Toxicologica, 51, 253-265. [Google Scholar] [CrossRef] [PubMed]
[36] Manolagas, S.C. (2000) Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis. Endocrine Reviews, 21, 115-137. [Google Scholar] [CrossRef] [PubMed]
[37] Chung, Y., Chen, Y., Weng, T., Yang, R. and Liu, S. (2019) Arsenic Induces Human Chondrocyte Senescence and Accelerates Rat Articular Cartilage Aging. Archives of Toxicology, 94, 89-101. [Google Scholar] [CrossRef] [PubMed]
[38] Farr, J.N., Fraser, D.G., Wang, H., Jaehn, K., Ogrodnik, M.B., Weivoda, M.M., et al. (2016) Identification of Senescent Cells in the Bone Microenvironment. Journal of Bone and Mineral Research, 31, 1920-1929. [Google Scholar] [CrossRef] [PubMed]
[39] Amuno, S., Al Kaissi, A., Jamwal, A., Niyogi, S. and Quenneville, C.E. (2018) Chronic Arsenicosis and Cadmium Exposure in Wild Snowshoe Hares (Lepus americanus) Breeding near Yellowknife, Northwest Territories (Canada), Part 2: Manifestation of Bone Abnormalities and Osteoporosis. Science of the Total Environment, 612, 1559-1567. [Google Scholar] [CrossRef] [PubMed]
[40] Amuno, S., Shekh, K., Kodzhahinchev, V., Niyogi, S. and Al Kaissi, A. (2021) Skeletal Pathology and Bone Mineral Density Changes in Wild Muskrats (Ondatra zibethicus) and Red Squirrels (Tamiasciurus hudsonicus) Inhabiting Arsenic Polluted Areas of Yellowknife, Northwest Territories (Canada): A Radiographic Densitometry Study. Ecotoxicology and Environmental Safety, 208, Article ID: 111721. [Google Scholar] [CrossRef] [PubMed]
[41] Hsieh, R., Huang, Y., Chen, W., Chen, H., Shiue, H., Lin, Y., et al. (2022) Associations between Plasma Folate and Vitamin B12, Blood Lead, and Bone Mineral Density among Adults and Elderly Who Received a Health Examination. Nutrients, 14, Article 911. [Google Scholar] [CrossRef] [PubMed]
[42] Zhang, Y., Chen, C., Wu, S., Nie, C., Hu, Y., Zhong, J., et al. (2025) Analysis of the Association between Mixed Exposure to Multiple Metals and Comorbidity of Osteopenia or Osteoporosis: Baseline Data from the Chinese Multi-Ethnic Cohort Study (CMEC). BMC Public Health, 25, Article No. 680. [Google Scholar] [CrossRef] [PubMed]
[43] Ling, R., Ai, Y., Chen, C., Zhang, J., Zou, Z., Cheng, S., et al. (2023) Risk of Environmental Chemicals on Bone Fractures Is Independent of Low Bone Mass in US Adults: Insights from 2017 to 2018 NHANES. Metabolites, 13, Article 346. [Google Scholar] [CrossRef] [PubMed]
[44] Banjabi, A.A., Kurunthachalam, K., Kumosani, T.A., Abulnaja, K.O., AL-Malki, A.L. and Moselhy, S.S. (2021) Serum Heavy Metals of Passive Smoker Females and Its Correlation to Bone Biomarkers and Risk of Osteoporosis. Environmental Science and Pollution Research, 29, 6943-6948. [Google Scholar] [CrossRef] [PubMed]
[45] Ximenez, J.P.B., Zamarioli, A., Kacena, M.A., Barbosa, R.M. and Barbosa Jr, F. (2020) Association of Urinary and Blood Concentrations of Heavy Metals with Measures of Bone Mineral Density Loss: A Data Mining Approach with the Results from the National Health and Nutrition Examination Survey. Biological Trace Element Research, 199, 92-101. [Google Scholar] [CrossRef] [PubMed]
[46] Akbal, A., Yılmaz, H. and Tutkun, E. (2013) Arsenic Exposure Associated with Decreased Bone Mineralization in Male. The Aging Male, 17, 256-258. [Google Scholar] [CrossRef] [PubMed]
[47] Xu, X., Lyu, J., Long, P., Liu, K., Wang, H., Wang, X., et al. (2023) Associations of Multiple Plasma Metals with Osteoporosis: Findings from the Dongfeng-Tongji Cohort. Environmental Science and Pollution Research, 30, 120903-120914. [Google Scholar] [CrossRef] [PubMed]
[48] Qin, L., Liu, Q., Zhang, T., Tang, X., Mo, X., Liang, Y., et al. (2023) Association between Combined Polymetallic Exposure and Osteoporosis. Biological Trace Element Research, 202, 3945-3958. [Google Scholar] [CrossRef] [PubMed]
[49] Hsueh, Y., Huang, Y., Chen, H., Shiue, H., Lin, Y. and Hsieh, R. (2021) Alcohol Consumption Moderated the Association between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss. Frontiers in Endocrinology, 12, Article 782174. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, J., Mai, Q., Di, D., Zhou, H., Zhang, R. and Wang, Q. (2023) Potential Roles of Gut Microbiota in Metal Mixture and Bone Mineral Density and Osteoporosis Risk Association: An Epidemiologic Study in Wuhan. Environmental Science and Pollution Research, 30, 117201-117213. [Google Scholar] [CrossRef] [PubMed]
[51] Galvez-Fernandez, M., Rodriguez-Hernandez, Z., Grau-Perez, M., Chaves, F.J., Garcia-Garcia, A.B., Amigo, N., et al. (2023) Metabolomic Patterns, Redox-Related Genes and Metals, and Bone Fragility Endpoints in the Hortega Study. Free Radical Biology and Medicine, 194, 52-61. [Google Scholar] [CrossRef] [PubMed]