2型糖尿病与骨质疏松症的研究进展
Research Progress on Type 2 Diabetes Mellitus and Osteoporosis
DOI: 10.12677/acm.2025.1561924, PDF,   
作者: 姜汶彤:山东第一医科大学(山东省医学科学院)研究生部(研究生教育中心),山东 济南;徐 进*:山东第一医科大学(山东省医学科学院)研究生部(研究生教育中心),山东 济南;山东第一医科大学附属省立医院内分泌科,山东 济南
关键词: 2型糖尿病骨质疏松症影响机制Type 2 Diabetes Mellitus Osteoporosis Influence Mechanism
摘要: 近年来,研究发现,与非糖尿病患者相比,2型糖尿病患者患骨质疏松症的风险增加,并且2型糖尿病人群中骨质疏松症的患病率正在逐年增高,2型糖尿病患者骨折风险显著增加,特别是髋部和腕部骨折。这可能与糖尿病使得骨折风险增加,骨折愈合延迟以及氧化应激、胰岛素抵抗等原因相关。本研究旨在探讨2型糖尿病与骨质疏松之间的关联,有助于更好地理解其病理机制,并为临床预防和治疗提供依据。
Abstract: In recent years, it has been found that people with type 2 diabetes have an increased risk of osteoporosis compared to non-diabetics, and that the prevalence of osteoporosis in the type 2 diabetic population is increasing every year, with people with type 2 diabetes being at a significantly increased risk of fracture, particularly hip and wrist fractures. This may be related to the fact that diabetes makes the risk of fracture increased, delayed fracture healing as well as oxidative stress, insulin resistance and other reasons. The aim of this study is to investigate the association between type 2 diabetes mellitus and osteoporosis, which will help to better understand its pathomechanisms and provide a basis for clinical prevention and treatment.
文章引用:姜汶彤, 徐进. 2型糖尿病与骨质疏松症的研究进展[J]. 临床医学进展, 2025, 15(6): 1854-1860. https://doi.org/10.12677/acm.2025.1561924

参考文献

[1] Wang, L., Peng, W., Zhao, Z., Zhang, M., Shi, Z., Song, Z., et al. (2021) Prevalence and Treatment of Diabetes in China, 2013-2018. Journal of the American Medical Association, 326, Article 2498. [Google Scholar] [CrossRef] [PubMed]
[2] Ensrud, K.E. and Crandall, C.J. (2017) Osteoporosis. Annals of Internal Medicine, 167, ITC17-ITC32. [Google Scholar] [CrossRef] [PubMed]
[3] Wang, L., Yu, W., Yin, X., Cui, L., Tang, S., Jiang, N., et al. (2021) Prevalence of Osteoporosis and Fracture in China. JAMA Network Open, 4, e2121106. [Google Scholar] [CrossRef] [PubMed]
[4] Hou, Y., Hou, X., Nie, Q., Xia, Q., Hu, R., Yang, X., et al. (2023) Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study. Diabetes, Metabolic Syndrome and Obesity, 16, 1177-1192. [Google Scholar] [CrossRef] [PubMed]
[5] Gao, L., Liu, C., Hu, P., Wang, N., Bao, X., Wang, B., et al. (2022) The Role of Advanced Glycation End Products in Fracture Risk Assessment in Postmenopausal Type 2 Diabetic Patients. Frontiers in Endocrinology, 13, Article 1013397. [Google Scholar] [CrossRef] [PubMed]
[6] Cavati, G., Pirrotta, F., Merlotti, D., Ceccarelli, E., Calabrese, M., Gennari, L., et al. (2023) Role of Advanced Glycation End-Products and Oxidative Stress in Type-2-Diabetes-Induced Bone Fragility and Implications on Fracture Risk Stratification. Antioxidants, 12, Article 928. [Google Scholar] [CrossRef] [PubMed]
[7] Zhang, W., Shen, X., Wan, C., Zhao, Q., Zhang, L., Zhou, Q., et al. (2012) Effects of Insulin and Insulin-Like Growth Factor 1 on Osteoblast Proliferation and Differentiation: Differential Signalling via Akt and Erk. Cell Biochemistry and Function, 30, 297-302. [Google Scholar] [CrossRef] [PubMed]
[8] Sheu, A., Greenfield, J.R., White, C.P. and Center, J.R. (2023) Contributors to Impaired Bone Health in Type 2 Diabetes. Trends in Endocrinology & Metabolism, 34, 34-48. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, R., Yang, C., Zhu, Q., Li, Y., Hu, H., Wang, D., et al. (2023) Comparison of the Effects of Metformin and Thiazolidinediones on Bone Metabolism: A Systematic Review and Meta-Analysis. Medicina, 59, Article 904. [Google Scholar] [CrossRef] [PubMed]
[10] Rajpathak, S.N., Fu, C., Brodovicz, K.G., Engel, S.S. and Lapane, K. (2015) Sulfonylurea Use and Risk of Hip Fractures among Elderly Men and Women with Type 2 Diabetes. Drugs & Aging, 32, 321-327. [Google Scholar] [CrossRef] [PubMed]
[11] Cortizo, A.M., Sedlinsky, C., McCarthy, A.D., Blanco, A. and Schurman, L. (2006) Osteogenic Actions of the Anti-Diabetic Drug Metformin on Osteoblasts in Culture. European Journal of Pharmacology, 536, 38-46. [Google Scholar] [CrossRef] [PubMed]
[12] Steppe, L., Megafu, M., Tschaffon-Müller, M.E.A., Ignatius, A. and Haffner-Luntzer, M. (2023) Fracture Healing Research: Recent Insights. Bone Reports, 19, Article 101686. [Google Scholar] [CrossRef] [PubMed]
[13] Chen, Y., Zhou, Y., Lin, J. and Zhang, S. (2022) Challenges to Improve Bone Healing under Diabetic Conditions. Frontiers in Endocrinology, 13, Article 861878. [Google Scholar] [CrossRef] [PubMed]
[14] Dhaliwal, R., Ewing, S.K., Vashishth, D., Semba, R.D. and Schwartz, A.V. (2020) Greater Carboxy-Methyl-Lysine Is Associated with Increased Fracture Risk in Type 2 Diabetes. Journal of Bone and Mineral Research, 37, 265-272. [Google Scholar] [CrossRef] [PubMed]
[15] Khosla, S., Samakkarnthai, P., Monroe, D.G. and Farr, J.N. (2021) Update on the Pathogenesis and Treatment of Skeletal Fragility in Type 2 Diabetes Mellitus. Nature Reviews Endocrinology, 17, 685-697. [Google Scholar] [CrossRef] [PubMed]
[16] Segura-Egea, J.J., Cabanillas-Balsera, D., Martín-González, J. and Cintra, L.T.A. (2022) Impact of Systemic Health on Treatment Outcomes in Endodontics. International Endodontic Journal, 56, 219-235. [Google Scholar] [CrossRef] [PubMed]
[17] Zhang, E., Miramini, S., Patel, M., Richardson, M., Ebeling, P. and Zhang, L. (2022) Role of TNF-α in Early-Stage Fracture Healing under Normal and Diabetic Conditions. Computer Methods and Programs in Biomedicine, 213, Article 106536. [Google Scholar] [CrossRef] [PubMed]
[18] Jeyabalan, J., Viollet, B., Smitham, P., Ellis, S.A., Zaman, G., Bardin, C., et al. (2013) The Anti-Diabetic Drug Metformin Does Not Affect Bone Mass in Vivo or Fracture Healing. Osteoporosis International, 24, 2659-2670. [Google Scholar] [CrossRef] [PubMed]
[19] Mu, W., Wang, Z., Ma, C., Jiang, Y., Zhang, N., Hu, K., et al. (2018) Metformin Promotes the Proliferation and Differentiation of Murine Preosteoblast by Regulating the Expression of Sirt6 and Oct4. Pharmacological Research, 129, 462-474. [Google Scholar] [CrossRef] [PubMed]
[20] Ruan, Z., Yin, H., Wan, T., Lin, Z., Zhao, S., Long, H., et al. (2023) Metformin Accelerates Bone Fracture Healing by Promoting Type H Vessel Formation through Inhibition of YAP1/TAZ Expression. Bone Research, 11, Article No. 45. [Google Scholar] [CrossRef] [PubMed]
[21] Guo, Y., Wei, J., Liu, C., Li, X. and Yan, W. (2023) Metformin Regulates Bone Marrow Stromal Cells to Accelerate Bone Healing in Diabetic Mice. eLife, 12, e88310. [Google Scholar] [CrossRef] [PubMed]
[22] Grewe, J.M., Knapstein, P., Donat, A., Jiang, S., Smit, D.J., Xie, W., et al. (2022) The Role of Sphingosine-1-Phosphate in Bone Remodeling and Osteoporosis. Bone Research, 10, Article No. 34. [Google Scholar] [CrossRef] [PubMed]
[23] Chen, X., Li, X., Yang, M., Song, Y. and Zhang, Y. (2018) Osteoprotective Effects of Salidroside in Ovariectomized Mice and Diabetic Mice. European Journal of Pharmacology, 819, 281-288. [Google Scholar] [CrossRef] [PubMed]
[24] Bhatti, J.S., Sehrawat, A., Mishra, J., Sidhu, I.S., Navik, U., Khullar, N., et al. (2022) Oxidative Stress in the Pathophysiology of Type 2 Diabetes and Related Complications: Current Therapeutics Strategies and Future Perspectives. Free Radical Biology and Medicine, 184, 114-134. [Google Scholar] [CrossRef] [PubMed]
[25] Black, H.S. (2022) A Synopsis of the Associations of Oxidative Stress, ROS, and Antioxidants with Diabetes Mellitus. Antioxidants, 11, Article 2003. [Google Scholar] [CrossRef] [PubMed]
[26] Chen, B., He, Q., Yang, J., Pan, Z., Xiao, J., Chen, W., et al. (2023) Metformin Suppresses Oxidative Stress Induced by High Glucose via Activation of the Nrf2/HO-1 Signaling Pathway in Type 2 Diabetic Osteoporosis. Life Sciences, 312, Article 121092. [Google Scholar] [CrossRef] [PubMed]
[27] Lee, Y., Lee, N., Bhattarai, G., Oh, Y., Yu, M., Yoo, I., et al. (2010) Enhancement of Osteoblast Biocompatibility on Titanium Surface with Terrein Treatment. Cell Biochemistry and Function, 28, 678-685. [Google Scholar] [CrossRef] [PubMed]
[28] Zhang, B., Yang, Y., Yi, J., Zhao, Z. and Ye, R. (2021) Hyperglycemia Modulates M1/M2 Macrophage Polarization via Reactive Oxygen Species Overproduction in Ligature-Induced Periodontitis. Journal of Periodontal Research, 56, 991-1005. [Google Scholar] [CrossRef] [PubMed]
[29] Barbagallo, I., Vanella, A., Peterson, S.J., Kim, D.H., Tibullo, D., Giallongo, C., et al. (2009) Overexpression of Heme Oxygenase-1 Increases Human Osteoblast Stem Cell Differentiation. Journal of Bone and Mineral Metabolism, 28, 276-288. [Google Scholar] [CrossRef] [PubMed]
[30] Domazetovic, V., Marcucci, G., Falsetti, I., Bilia, A.R., Vincenzini, M.T., Brandi, M.L., et al. (2020) Blueberry Juice Antioxidants Protect Osteogenic Activity against Oxidative Stress and Improve Long-Term Activation of the Mineralization Process in Human Osteoblast-Like Saos-2 Cells: Involvement of Sirt1. Antioxidants, 9, Article 125. [Google Scholar] [CrossRef] [PubMed]
[31] Cao, X., Luo, D., Li, T., Huang, Z., Zou, W., Wang, L., et al. (2019) MnTBAP Inhibits Bone Loss in Ovariectomized Rats by Reducing Mitochondrial Oxidative Stress in Osteoblasts. Journal of Bone and Mineral Metabolism, 38, 27-37. [Google Scholar] [CrossRef] [PubMed]
[32] Domazetovic, V., Marcucci, G., Pierucci, F., Bruno, G., Di Cesare Mannelli, L., Ghelardini, C., et al. (2019) Blueberry Juice Protects Osteocytes and Bone Precursor Cells against Oxidative Stress Partly through Sirt1. FEBS Open Bio, 9, 1082-1096. [Google Scholar] [CrossRef] [PubMed]
[33] Mohamad, N., Ima-Nirwana, S. and Chin, K. (2020) Are Oxidative Stress and Inflammation Mediators of Bone Loss Due to Estrogen Deficiency? A Review of Current Evidence. Endocrine, Metabolic & Immune Disorders-Drug Targets, 20, 1478-1487. [Google Scholar] [CrossRef] [PubMed]
[34] Ru, J. and Wang, Y. (2020) Osteocyte Apoptosis: The Roles and Key Molecular Mechanisms in Resorption-Related Bone Diseases. Cell Death & Disease, 11, Article No. 846. [Google Scholar] [CrossRef] [PubMed]
[35] Barrett-Connor, E. and Kritz-Silverstein, D. (1996) Does Hyperinsulinemia Preserve Bone? Diabetes Care, 19, 1388-1392. [Google Scholar] [CrossRef] [PubMed]
[36] Verhaeghe, J., Herck, E.V., Visser, W.J., Suiker, A.M.H., Thomasset, M., Einhorn, T.A., et al. (1990) Bone and Mineral Metabolism in BB Rats with Long-Term Diabetes: Decreased Bone Turnover and Osteoporosis. Diabetes, 39, 477-482. [Google Scholar] [CrossRef] [PubMed]
[37] 袁志发, 张通, 蔡金池, 等. 肠道菌群、IGF-1与骨代谢联系机制的研究进展[J]. 中国骨质疏松杂志, 2021, 27(4): 599-604.
[38] Hou, J.C., Zernicke, R.F. and Barnard, R.J. (1993) Effects of Severe Diabetes and Insulin on the Femoral Neck of the Immature Rat. Journal of Orthopaedic Research, 11, 263-271. [Google Scholar] [CrossRef] [PubMed]
[39] Strotmeyer, E.S., Cauley, J.A., Schwartz, A.V., Nevitt, M.C., Resnick, H.E., Bauer, D.C., et al. (2005) Nontraumatic Fracture Risk with Diabetes Mellitus and Impaired Fasting Glucose in Older White and Black Adults. Archives of Internal Medicine, 165, Article 1612-1617. [Google Scholar] [CrossRef] [PubMed]
[40] Lawlor, D.A., Sattar, N., Sayers, A. and Tobias, J.H. (2012) The Association of Fasting Insulin, Glucose, and Lipids with Bone Mass in Adolescents: Findings from a Cross-Sectional Study. The Journal of Clinical Endocrinology & Metabolism, 97, 2068-2076. [Google Scholar] [CrossRef] [PubMed]
[41] Yang, J., Hong, N., Shim, J., Rhee, Y. and Kim, H.C. (2018) Association of Insulin Resistance with Lower Bone Volume and Strength Index of the Proximal Femur in Nondiabetic Postmenopausal Women. Journal of Bone Metabolism, 25, 123-132. [Google Scholar] [CrossRef] [PubMed]
[42] Isfort, M., Stevens, S.C.W., Schaffer, S., Jong, C.J. and Wold, L.E. (2013) Metabolic Dysfunction in Diabetic Cardiomyopathy. Heart Failure Reviews, 19, 35-48. [Google Scholar] [CrossRef] [PubMed]
[43] Singh, H.J. and Garland, H.O. (1989) A Comparison of the Effects of Oral and Intravenous Glucose Administration on Renal Calcium Excretion in the Rat. Quarterly Journal of Experimental Physiology, 74, 531-540. [Google Scholar] [CrossRef] [PubMed]
[44] Verhaeghe, J., Bouillon, R., Nyomba, B.L., Lissens, W. and Assche, F.A.V. (1986) Vitamin D and Bone Mineral Homeostasis during Pregnancy in the Diabetic BB Rat. Endocrinology, 118, 1019-1025. [Google Scholar] [CrossRef] [PubMed]
[45] Elafros, M.A., Andersen, H., Bennett, D.L., Savelieff, M.G., Viswanathan, V., Callaghan, B.C., et al. (2022) Towards Prevention of Diabetic Peripheral Neuropathy: Clinical Presentation, Pathogenesis, and New Treatments. The Lancet Neurology, 21, 922-936. [Google Scholar] [CrossRef] [PubMed]
[46] Henning, R.J. (2018) Type-2 Diabetes Mellitus and Cardiovascular Disease. Future Cardiology, 14, 491-509. [Google Scholar] [CrossRef] [PubMed]
[47] Cai, K., Liu, Y. and Wang, D. (2022) Prevalence of Diabetic Retinopathy in Patients with Newly Diagnosed Type 2 Diabetes: A Systematic Review and Meta-Analysis. Diabetes/Metabolism Research and Reviews, 39, e3586. [Google Scholar] [CrossRef] [PubMed]
[48] Ramirez-Perdomo, C., Perdomo-Romero, A. and Rodríguez-Vélez, M. (2019) Conhecimentos e práticas para a prevenção do pé diabético. Revista Gaúcha de Enfermagem, 40, e20180161. [Google Scholar] [CrossRef] [PubMed]