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糖尿病致骨质疏松的相关机制、骨质风险评估及治疗进展
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Abstract:
糖尿病是一种全球性健康问题，与骨质疏松症的发病风险增加密切相关。本综述深入探讨了糖尿病患者罹患骨质疏松症的相关机制，包括胰岛素缺乏、高胰岛素血症、高血糖水平、炎症因子和氧化应激等因素。并综述了骨密度(BMD)、生化标志物以及骨折预测模型(例如FRAX)、骨小梁评分等风险评估工具在糖尿病人群中的应用，讨论了部分降糖药物可能对骨骼健康产生的不利影响以及各种抗骨质疏松治疗策略在该特定患者群体中的有效性。
Diabetes mellitus is a global health issue closely associated with an increased risk of developing osteoporosis. This review delves into the mechanisms by which diabetic patients develop osteoporosis, including the effects of insulin deficiency, hyperinsulinemia, hyperglycemia, inflammatory factors, and oxidative stress on bone health. Additionally, it summarizes the application of risk assessment tools such as bone mineral density (BMD), biochemical markers, fracture prediction models (such as FRAX), and trabecular bone score (TBS) in the diabetic population. The review also discusses the potential adverse effects of certain antidiabetic medications on bone health and evaluates the effectiveness of various osteoporosis treatment strategies in this specific patient group.
| [1] | Kong, X., Zhao, Z., Zhang, D., Xie, R., Sun, L., Zhao, H., et al. (2022) Major Osteoporosis Fracture Prediction in Type 2 Diabetes: A Derivation and Comparison Study. Osteoporosis International, 33, 1957-1967. https://doi.org/10.1007/s00198-022-06425-8 |
| [2] | Weber, D.R., Haynes, K., Leonard, M.B., Willi, S.M. and Denburg, M.R. (2015) Type 1 Diabetes Is Associated with an Increased Risk of Fracture across the Life Span: A Population-Based Cohort Study Using the Health Improvement Network (Thin). Diabetes Care, 38, 1913-1920. https://doi.org/10.2337/dc15-0783 |
| [3] | Vestergaard, P., Rejnmark, L. and Mosekilde, L. (2005) Relative Fracture Risk in Patients with Diabetes Mellitus, and the Impact of Insulin and Oral Antidiabetic Medication on Relative Fracture Risk. Diabetologia, 48, 1292-1299. https://doi.org/10.1007/s00125-005-1786-3 |
| [4] | Bonds, D.E., Larson, J.C., Schwartz, A.V., Strotmeyer, E.S., Robbins, J., Rodriguez, B.L., et al. (2006) Risk of Fracture in Women with Type 2 Diabetes: The Women’s Health Initiative Observational Study. The Journal of Clinical Endocrinology & Metabolism, 91, 3404-3410. https://doi.org/10.1210/jc.2006-0614 |
| [5] | Hans, D., Goertzen, A.L., Krieg, M. and Leslie, W.D. (2011) Bone Microarchitecture Assessed by TBS Predicts Osteoporotic Fractures Independent of Bone Density: The Manitoba Study. Journal of Bone and Mineral Research, 26, 2762-2769. https://doi.org/10.1002/jbmr.499 |
| [6] | Valderrábano, R.J. and Linares, M.I. (2018) Diabetes Mellitus and Bone Health: Epidemiology, Etiology and Implications for Fracture Risk Stratification. Clinical Diabetes and Endocrinology, 4, Article No. 9. https://doi.org/10.1186/s40842-018-0060-9 |
| [7] | Bai, J., Gao, Q., Wang, C. and Dai, J. (2019) Diabetes Mellitus and Risk of Low-Energy Fracture: A Meta-Analysis. Aging Clinical and Experimental Research, 32, 2173-2186. https://doi.org/10.1007/s40520-019-01417-x |
| [8] | Hamann, C., Kirschner, S., Günther, K. and Hofbauer, L.C. (2012) Bone, Sweet Bone—Osteoporotic Fractures in Diabetes Mellitus. Nature Reviews Endocrinology, 8, 297-305. https://doi.org/10.1038/nrendo.2011.233 |
| [9] | Bełtowski, J., Wójcicka, G. and Jamroz-Wiśniewska, A. (2018) Hydrogen Sulfide in the Regulation of Insulin Secretion and Insulin Sensitivity: Implications for the Pathogenesis and Treatment of Diabetes Mellitus. Biochemical Pharmacology, 149, 60-76. https://doi.org/10.1016/j.bcp.2018.01.004 |
| [10] | Gaudio, A., Privitera, F., Battaglia, K., Torrisi, V., Sidoti, M.H., Pulvirenti, I., et al. (2012) Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus. The Journal of Clinical Endocrinology & Metabolism, 97, 3744-3750. https://doi.org/10.1210/jc.2012-1901 |
| [11] | Ivers, R.Q., Cumming, R.G., Mitchell, P. and Peduto, A.J. (2001) Diabetes and Risk of Fracture: The Blue Mountains Eye Study. Diabetes Care, 24, 1198-1203. https://doi.org/10.2337/diacare.24.7.1198 |
| [12] | Melton, L.J., Leibson, C.L., Achenbach, S.J., Therneau, T.M. and Khosla, S. (2008) Fracture Risk in Type 2 Diabetes: Update of a Population-Based Study. Journal of Bone and Mineral Research, 23, 1334-1342. https://doi.org/10.1359/jbmr.080323 |
| [13] | Kanis, J.A. (2008) Assessment of Osteoporosis at the Primary Health Care Level. World Health Organization Scientific Group. University of Sheffield, WHO Collaborating Centre for Metabolic Bone Diseases. |
| [14] | Li, C., Liu, C., Lin, W., Meng, N., Chen, C., Yang, S., et al. (2015) Glycated Hemoglobin Level and Risk of Hip Fracture in Older People with Type 2 Diabetes: A Competing Risk Analysis of Taiwan Diabetes Cohort Study. Journal of Bone and Mineral Research, 30, 1338-1346. https://doi.org/10.1002/jbmr.2462 |
| [15] | Sarodnik, C., Bours, S.P.G., Schaper, N.C., van den Bergh, J.P. and van Geel, T.A.C.M. (2018) The Risks of Sarcopenia, Falls and Fractures in Patients with Type 2 Diabetes Mellitus. Maturitas, 109, 70-77. https://doi.org/10.1016/j.maturitas.2017.12.011 |
| [16] | Kim, T.N., Park, M.S., Yang, S.J., Yoo, H.J., Kang, H.J., Song, W., et al. (2010) Prevalence and Determinant Factors of Sarcopenia in Patients with Type 2 Diabetes: The Korean Sarcopenic Obesity Study (KSOS). Diabetes Care, 33, 1497-1499. https://doi.org/10.2337/dc09-2310 |
| [17] | Sriruanthong, K., Philawuth, N., Saloa, S., Daraphongsataporn, N. and Sucharitpongpan, W. (2022) Risk Factors of Refracture after a Fragility Fracture in Elderly. Archives of Osteoporosis, 17, Article No. 98. https://doi.org/10.1007/s11657-022-01143-4 |
| [18] | Eller-Vainicher, C., Falchetti, A., Gennari, L., Cairoli, E., Bertoldo, F., Vescini, F., et al. (2019) Diagnosis of Endocrine Disease: Evaluation of Bone Fragility in Endocrine Disorders. European Journal of Endocrinology, 180, R213-R232. https://doi.org/10.1530/eje-18-0991 |
| [19] | Hough, F.S., Pierroz, D.D., Cooper, C., Ferrari, S.L. (2016) Mechanisms in Endocrinology: Mechanisms and Evaluation of Bone Fragility in Type 1 Diabetes Mellitus. European Journal of Endocrinology, 174, R127-R138. https://doi.org/10.1530/eje-15-0820 |
| [20] | Kanis, J.A., Cooper, C., Rizzoli, R. and Reginster, J. (2018) European Guidance for the Diagnosis and Management of Osteoporosis in Postmenopausal Women. Osteoporosis International, 30, 3-44. https://doi.org/10.1007/s00198-018-4704-5 |
| [21] | Popp, A.W., Meer, S., Krieg, M., Perrelet, R., Hans, D. and Lippuner, K. (2015) Bone Mineral Density (BMD) and Vertebral Trabecular Bone Score (TBS) for the Identification of Elderly Women at High Risk for Fracture: The SEMOF Cohort Study. European Spine Journal, 25, 3432-3438. https://doi.org/10.1007/s00586-015-4035-6 |
| [22] | Ferrari, S.L., Abrahamsen, B., Napoli, N., Akesson, K., Chandran, M., Eastell, R., et al. (2018) Diagnosis and Management of Bone Fragility in Diabetes: An Emerging Challenge. Osteoporosis International, 29, 2585-2596. https://doi.org/10.1007/s00198-018-4650-2 |
| [23] | Kanis, J.A., Johansson, H., Oden, A., Johnell, O., De Laet, C., Eisman, J.A., et al. (2004) A Family History of Fracture and Fracture Risk: A Meta-Analysis. Bone, 35, 1029-1037. https://doi.org/10.1016/j.bone.2004.06.017 |
| [24] | Shah, V.N., Sippl, R., Joshee, P., Pyle, L., Kohrt, W.M., Schauer, I.E., et al. (2017) Trabecular Bone Quality Is Lower in Adults with Type 1 Diabetes and Is Negatively Associated with Insulin Resistance. Osteoporosis International, 29, 733-739. https://doi.org/10.1007/s00198-017-4353-0 |
| [25] | Patsch, J.M., Burghardt, A.J., Yap, S.P., Baum, T., Schwartz, A.V., Joseph, G.B., et al. (2012) Increased Cortical Porosity in Type 2 Diabetic Postmenopausal Women with Fragility Fractures. Journal of Bone and Mineral Research, 28, 313-324. https://doi.org/10.1002/jbmr.1763 |
| [26] | Jiang, N. and Xia, W. (2018) Assessment of Bone Quality in Patients with Diabetes Mellitus. Osteoporosis International, 29, 1721-1736. https://doi.org/10.1007/s00198-018-4532-7 |
| [27] | Napoli, N., Chandran, M., Pierroz, D.D., Abrahamsen, B., Schwartz, A.V. and Ferrari, S.L. (2016) Mechanisms of Diabetes Mellitus-Induced Bone Fragility. Nature Reviews Endocrinology, 13, 208-219. https://doi.org/10.1038/nrendo.2016.153 |
| [28] | Napoli, N., Strotmeyer, E.S., Ensrud, K.E., Sellmeyer, D.E., Bauer, D.C., Hoffman, A.R., et al. (2014) Fracture Risk in Diabetic Elderly Men: The Mros Study. Diabetologia, 57, 2057-2065. https://doi.org/10.1007/s00125-014-3289-6 |
| [29] | Kostev, K., Pscherer, S., Rathmann, W. and Dippel, F. (2016) Fracture Risk in Patients with Type 2 Diabetes under Different Antidiabetic Treatment Regimens: A Retrospective Database Analysis in Primary Care. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 9, 17-23. https://doi.org/10.2147/dmso.s101370 |
| [30] | Xue, X., Li, Z. and Zhao, M. (2022) Metformin and Lipopolysaccharide Regulate Transcription of NFATc2 Gene via the Transcription Factor RUNX2. Journal of Southern Medical University, 42, 425-431. |
| [31] | Komori, T. (2022) Whole Aspect of Runx2 Functions in Skeletal Development. International Journal of Molecular Sciences, 23, Article 5776. https://doi.org/10.3390/ijms23105776 |
| [32] | Palermo, A., D’Onofrio, L., Eastell, R., Schwartz, A.V., Pozzilli, P. and Napoli, N. (2015) Oral Anti-Diabetic Drugs and Fracture Risk, Cut to the Bone: Safe or Dangerous? A Narrative Review. Osteoporosis International, 26, 2073-2089. https://doi.org/10.1007/s00198-015-3123-0 |
| [33] | Napoli, N., Chandran, M., Pierroz, D.D., Abrahamsen, B., Schwartz, A.V. and Ferrari, S.L. (2016) Mechanisms of Diabetes Mellitus-Induced Bone Fragility. Nature Reviews Endocrinology, 13, 208-219. https://doi.org/10.1038/nrendo.2016.153 |
| [34] | Ruanpeng, D., Ungprasert, P., Sangtian, J. and Harindhanavudhi, T. (2017) Sodium‐Glucose Cotransporter 2 (SGLT2) Inhibitors and Fracture Risk in Patients with Type 2 Diabetes Mellitus: A Meta‐Analysis. Diabetes/Metabolism Research and Reviews, 33, e2903. https://doi.org/10.1002/dmrr.2903 |
| [35] | Watts, N.B., Bilezikian, J.P., Usiskin, K., Edwards, R., Desai, M., Law, G., et al. (2016) Effects of Canagliflozin on Fracture Risk in Patients with Type 2 Diabetes Mellitus. The Journal of Clinical Endocrinology & Metabolism, 101, 157-166. https://doi.org/10.1210/jc.2015-3167 |
| [36] | Su, B., Sheng, H., Zhang, M., Bu, L., Yang, P., Li, L., et al. (2014) Risk of Bone Fractures Associated with Glucagon-Like Peptide-1 Receptor Agonists’ Treatment: A Meta-Analysis of Randomized Controlled Trials. Endocrine, 48, 107-115. https://doi.org/10.1007/s12020-014-0361-4 |
| [37] | Mohsin, S., Baniyas, M.M., AlDarmaki, R.S., Tekes, K., Kalász, H. and Adeghate, E.A. (2019) An Update on Therapies for the Treatment of Diabetes-Induced Osteoporosis. Expert Opinion on Biological Therapy, 19, 937-948. https://doi.org/10.1080/14712598.2019.1618266 |
| [38] | 王露, 刘伟兵, 钟嘉伟, 廖翔, 徐王兵. 骨质疏松症药物治疗的现状和研究进展[J]. 中国现代医生, 2024, 62(27): 124-128. |
| [39] | Lyu, H., Zhao, S.S., Zhang, L., Wei, J., Li, X., Li, H., et al. (2023) Denosumab and Incidence of Type 2 Diabetes among Adults with Osteoporosis: Population Based Cohort Study. BMJ, 381, e073435. https://doi.org/10.1136/bmj-2022-073435 |
| [40] | Pagnotti, G.M., Styner, M., Uzer, G., Patel, V.S., Wright, L.E., Ness, K.K., et al. (2019) Combating Osteoporosis and Obesity with Exercise: Leveraging Cell Mechanosensitivity. Nature Reviews Endocrinology, 15, 339-355. https://doi.org/10.1038/s41574-019-0170-1 |
