地舒单抗在骨质疏松中的应用研究进展
Research Progress on the Application of Deshumazumab in Osteoporosis
DOI: 10.12677/ACM.2023.1381879, PDF,   
作者: 马 宁:新疆医科大学研究生院,新疆 乌鲁木齐;新疆维吾尔自治区人民医院骨科关节与运动科,新疆 乌鲁木齐;张浩沙强*, 王志刚, 李 坤:新疆维吾尔自治区人民医院骨科关节与运动科,新疆 乌鲁木齐
关键词: 地舒单抗骨质疏松核因子κB受体Deschumab Osteoporosis Nuclear Factor Kappa B Receptor
摘要: 在全球老龄化背景下,骨质疏松成为了一个公众健康问题。骨质疏松是一种骨稳态失衡的全身性骨疾病,地舒单抗作为首个核因子κB受体活化因子配体(receptor activator nuclear of factor kappa-B ligand, RANKL)抑制剂应用于骨质疏松治疗取得不错的疗效。虽然在中国2020年上市,但国外已有10余年的临床应用经验和大量的相关研究,可预见其在中国的应用也会越来越广泛。现将地舒单抗在骨质疏松中的应用及研究进展予以综述。
Abstract: In the context of global aging, osteoporosis has become a public health problem. Osteoporosis is a systemic bone disease with bone homeostasis imbalance. As the first inhibitor of nuclear factor kappa B receptor activating factor ligand, deschumab has achieved good results in the treatment of osteoporosis. Although it is listed in China in 2020, it has more than 10 years of clinical application experience and a large number of related researches abroad, and it can be predicted that it will be more and more widely used in China. In this paper, the application and research progress of desuximab in osteoporosis are reviewed.
文章引用:马宁, 张浩沙强, 王志刚, 李坤. 地舒单抗在骨质疏松中的应用研究进展[J]. 临床医学进展, 2023, 13(8): 13454-13463. https://doi.org/10.12677/ACM.2023.1381879

参考文献

[1] 柴波, 冯皓宇, 常强, 杨卓. 中国各地区绝经后骨质疏松症患病率及骨密度测量检出率分析[J]. 实用骨科杂志, 2020, 26(9): 792-796.
[2] Yan, C., Zhang, J., An, F., et al. (2022) Research Progress of Ferroptosis Regulatory Net-work and Bone Remodeling in Osteoporosis. Frontiers in Public Health, 10, Article 910675. [Google Scholar] [CrossRef] [PubMed]
[3] Xiao, P.-L., Hsu, C.-J., Ma, Y.-G., et al. (2022) Prevalence and Treatment Rate of Osteoporosis in Patients Undergoing Total Knee and Hip Arthroplasty: A Systematic Review and Me-ta-Analysis. Archives of Osteoporosis, 17, Article No. 16. [Google Scholar] [CrossRef] [PubMed]
[4] Bernatz, J.T., Brooks, A.E., Squire, M.W., et al. (2019) Osteo-porosis Is Common and Undertreated Prior to Total Joint Arthroplasty. The Journal of Arthroplasty, 34, 1347-1353. [Google Scholar] [CrossRef] [PubMed]
[5] Noh, J.-Y., Yang, Y. and Jung, H. (2020) Molecular Mechanisms and Emerging Therapeutics for Osteoporosis. International Journal of Molecular Sciences, 21, Article No. 7623. [Google Scholar] [CrossRef] [PubMed]
[6] Okagu, I.U., Ezeorba, T.P.C., Aguchem, R.N., et al. (2022) A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases. International Journal of Mo-lecular Sciences, 23, Article No. 8468. [Google Scholar] [CrossRef] [PubMed]
[7] Yasuda, H. (2019) [The Mechanism of Anti-RANKL Antibody in the Treatment of Metabolic Bone Diseases Including Osteoporosis—Possible Applications of Anti-RANKL Antibody to the Treatment of Cancer Patients]. Nihon Yakurigaku Zasshi, 153, 11-15. (In Japanese) [Google Scholar] [CrossRef] [PubMed]
[8] 陈文文, 姜娟, 尹玲, 等. 核因子κB受体活化体配体抑制剂地舒单抗在绝经后女性骨质疏松症治疗中的研究进展[J]. 中国医院药学杂志, 2021, 41(12): 1267-1270.
[9] Lee, D.H. and Kim, M. (2023) Comparative Study of Lumbar Bone Mineral Content Using DXA and CT Hounsfield Unit Values in Chest CT. BMC Musculoskeletal Disorders, 24, Article No. 94. [Google Scholar] [CrossRef] [PubMed]
[10] Gao, S. and Zhao, Y. (2022) Quality of Life in Postmenopausal Women with Osteoporosis: A Systematic Review and Meta-Analysis. Quality of Life Research, 32, 1551-1565. [Google Scholar] [CrossRef] [PubMed]
[11] Mohamad, N.-V., Ima-Nirwana, S. and Chin, K.-Y. (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]
[12] Soysa, N.S. and Alles, N. (2019) Positive and Nega-tive Regulators of Osteoclast Apoptosis. Bone Reports, 11, Article ID: 100225. [Google Scholar] [CrossRef] [PubMed]
[13] Bonaccorsi, G., Piva, I., Greco, P. and Cervellati, C. (2019) Oxi-dative Stress as a Possible Pathogenic Cofactor of Post-Menopausal Osteoporosis: Existing Evidence in Support of the Axis Oestrogen Deficiency-Redox Imbalance-Bone Loss. Indian Journal of Medical Research, 147, 341-351. [Google Scholar] [CrossRef
[14] Marques-Carvalho, A., Sardão, V.A., Kim, H.-N. and Almeida, M. (2023) ECSIT Is Essential for RANKL-Induced Stimulation of Mitochondria in Osteoclasts and a Target for the An-ti-Osteoclastogenic Effects of Estrogens. Frontiers in Endocrinology, 14, Article 1110369. [Google Scholar] [CrossRef] [PubMed]
[15] Urquiaga, M. and Saag, K.G. (2022) Risk for Osteoporosis and Fracture with Glucocorticoids. Best Practice & Research Clinical Rheumatology, 36, Article ID: 101793. [Google Scholar] [CrossRef] [PubMed]
[16] Chevalley, T. and Rizzoli, R. (2022) Acquisition of Peak Bone Mass. Best Practice & Research Clinical Endocrinology & Metabolism, 36, Article ID: 101616. [Google Scholar] [CrossRef] [PubMed]
[17] Wang, G., Wan, L., Zhang, L., Yan, C. and Zhang, Y. (2021) MicroRNA-133a Regulates the Viability and Differentiation Fate of Bone Marrow Mesenchymal Stem Cells via MAPK/ERK Signaling Pathway by Targeting FGFR1. DNA and Cell Biology, 40, 1112-1123. [Google Scholar] [CrossRef] [PubMed]
[18] He, Y., Huang, J., Jiang, G., et al. (2021) Menarche Age Exceed 17 Years and Menopausal Age Smaller than 48 Years May Affect Prevalence of Osteoporosis for Chinese Women. Ar-chives of Osteoporosis, 16, Article No. 123. [Google Scholar] [CrossRef] [PubMed]
[19] Chandra, A. and Rajawat, J. (2021) Skeletal Aging and Osteo-porosis: Mechanisms and Therapeutics. International Journal of Molecular Sciences, 22, Article No. 3553. [Google Scholar] [CrossRef] [PubMed]
[20] Rasch, L.A., de van der Schueren, M.A., van Tuyl, L.H., et al. (2017) Content Validity of a Short Calcium Intake List to Estimate Daily Dietary Calcium Intake of Patients with Osteoporosis. Calcified Tissue International, 100, 271-277. [Google Scholar] [CrossRef] [PubMed]
[21] Bouillon, R., Marcocci, C., Carmeliet, G., et al. (2019) Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocrine Reviews, 40, 1109-1151. [Google Scholar] [CrossRef] [PubMed]
[22] Silva, I.C.J. and Lazaretti-Castro, M. (2022) Vitamin D Metabolism and Extraskeletal Outcomes: An Update. Archives of Endocrinology and Metabolism, 66, 748-755. [Google Scholar] [CrossRef] [PubMed]
[23] Tuna, F., Akleylek, C., Özdemir, H. and Kabayel, D.D. (2020) Risk Factors, Fractures, and Management of Pregnancy-Associated Osteoporosis: A Retrospective Study of 14 Turkish Patients. Gynecological Endocrinology, 36, 238-242. [Google Scholar] [CrossRef] [PubMed]
[24] Sobh, M.M., Abdalbary, M., Elnagar, S., et al. (2022) Sec-ondary Osteoporosis and Metabolic Bone Diseases. Journal of Clinical Medicine, 11, Article No. 2382. [Google Scholar] [CrossRef] [PubMed]
[25] Ono, Y., Miyakoshi, N., Kasukawa, Y., et al. (2020) Diagnosis of Presarcopenia Using Body Height and Arm Span for Postmenopausal Osteoporosis. Clinical Interventions in Aging, 15, 357-361. [Google Scholar] [CrossRef
[26] Papageorgiou, M., Sathyapalan, T., and Schutte, R. (2019) Muscle Mass Measures and Incident Osteoporosis in a Large Cohort of Postmenopausal Women. Journal of Cachexia, Sarcopenia and Muscle, 10, 131-139. [Google Scholar] [CrossRef] [PubMed]
[27] Kirk, B., Feehan, J., Lombardi, G. and Duque, G. (2020) Muscle, Bone, and Fat Crosstalk: The Biological Role of Myokines, Osteokines, and Adipokines. Current Osteoporosis Reports, 18, 388-400. [Google Scholar] [CrossRef] [PubMed]
[28] Rolvien, T. and Amling, M. (2022) Disuse Osteoporosis: Clini-cal and Mechanistic Insights. Calcified Tissue International, 110, 592-604. [Google Scholar] [CrossRef] [PubMed]
[29] Fu, W. and Fan, J. (2021) Intervention Effect of Exercise Reha-bilitation Therapy on Patients with Type 2 Diabetic Osteoporosis. American Journal of Translational Research, 13, 3400-3408.
[30] Salari, N., Ghasemi, H., Mohammadi, L., et al. (2021) The Global Prevalence of Osteoporosis in the World: A Comprehensive Systematic Review and Meta-Analysis. Journal of Orthopaedic Surgery and Research, 16, Article No. 609. [Google Scholar] [CrossRef] [PubMed]
[31] 葛继荣, 王和鸣, 郑洪新, 等. 中医药防治原发性骨质疏松症专家共识(2020) [J]. 中国骨质疏松杂志, 2020, 26(12): 1717-1725.
[32] You, R., Mori, T., Ke, L., et al. (2021) Which Injected Antiosteoporotic Medication Is Worth Paying For? A Cost-Effectiveness Analysis of Teriparatide, Zoledronate, Ibandronate, and Denosumab for Postmenopausal Osteoporotic Women in China. Menopause, 29, 210-218. [Google Scholar] [CrossRef
[33] Gregson, C.L., Armstrong, D.J., Bowden, J., et al. (2022) UK Clinical Guideline for the Prevention and Treatment of Osteoporosis. Archives of Osteoporosis, 17, 58. [Google Scholar] [CrossRef] [PubMed]
[34] Matsumoto, T., Yamamoto, K., Takeuchi, T., et al. (2020) Elde-calcitol Is Superior to Alfacalcidol in Maintaining Bone Mineral Density in Glucocorticoid-Induced Osteoporosis Patients (e-GLORIA). Journal of Bone and Mineral Metabolism, 38, 522-532. [Google Scholar] [CrossRef] [PubMed]
[35] Su, S., He, N., Men, P., Song, C. and Zhai, S. (2019) The Effi-cacy and Safety of Menatetrenone in the Management of Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Osteoporosis International, 30, 1175-1186. [Google Scholar] [CrossRef] [PubMed]
[36] Hernandez, A.V., Pérez-López, F.R., Piscoya, A., et al. (2019) Comparative Efficacy of Bone Anabolic Therapies in Women with Postmenopausal Osteoporosis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Maturitas, 129, 12-22. [Google Scholar] [CrossRef] [PubMed]
[37] Dai, Z., Fang, P., Yan, X., et al. (2021) Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women with Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study. Frontiers in Pharmacology, 12, Article 770073. [Google Scholar] [CrossRef] [PubMed]
[38] 刘倩倩, 李春霖, 龚燕平. 老年男性骨质疏松症综合防治策略及指南解读[J]. 中国医药科学, 2021, 11(19): 23-28.
[39] 陈天洪, 李景峰. RANKL/RANK通路及其靶向药物地诺单抗在骨科疾病中的应用[J]. 骨科, 2022, 13(2): 181-187.
[40] 张薇, 熊斌彬, 李冰枝, 林海鸣. 骨质疏松症相关信号通路的研究进展[J]. 福建中医药, 2022, 53(9): 59-63.
[41] Li, H., Xiao, Z., Quarles, L.D. and Li, W. (2021) Osteoporosis: Mechanism, Molecular Target and Current Status on Drug Development. Current Medicinal Chemistry, 28, 1489-1507. [Google Scholar] [CrossRef] [PubMed]
[42] Udagawa, N., Koide, M., Nakamura, M., et al. (2021) Osteoclast Differentiation by RANKL and OPG Signaling Pathways. Journal of Bone and Mineral Metabolism, 39, 19-26. [Google Scholar] [CrossRef] [PubMed]
[43] Passaponti, S., Ermini, L., Acconci, G., et al. (2022) Rank-Rankl-Opg Axis in Multiple Sclerosis: The Contribution of Placenta. Cells, 11, Article No. 1357. [Google Scholar] [CrossRef] [PubMed]
[44] Bilezikian, J.P., Lin, C.J.F., Brown, J.P., et al. (2019) Long-Term Denosumab Treatment Restores Cortical Bone Loss and Reduces Fracture Risk at the Forearm and Humerus: Analyses from the FREEDOM Extension Cross-Over Group. Osteoporosis International, 30, 1855-1864. [Google Scholar] [CrossRef] [PubMed]
[45] Eastell, R., Rosen, C.J., Black, D.M., et al. (2019) Pharmaco-logical Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 104, 1595-1622. [Google Scholar] [CrossRef] [PubMed]
[46] Behanova, M., Reichardt, B., Stamm, T.A., et al. (2019) Treatment Ef-fects of Bisphosphonates and Denosumab on Survival and Refracture from Real-World Data of Hip-Fractured Patients. Calcified Tissue International, 105, 630-641. [Google Scholar] [CrossRef] [PubMed]
[47] Anastasilakis, A.D., Polyzos, S.A., Efstathiadou, Z.A., et al. (2015) Denosumab in Treatment-Naïve and Pre-Treated with Zoledronic Acid Postmenopausal Women with Low Bone Mass: Effect on Bone Mineral Density and Bone Turnover Markers. Metabolism, 64, 1291-1297. [Google Scholar] [CrossRef] [PubMed]
[48] Beaudoin, C., Jean, S., Bessette, L., et al. (2016) Denosumab Compared to Other Treatments to Prevent or Treat Osteoporosis in Individuals at Risk of Fracture: A Systematic Review and Meta-Analysis. Osteoporosis International, 27, 2835-2844. [Google Scholar] [CrossRef] [PubMed]
[49] Morizio, P., Burkhart, J.I. and Ozawa, S. (2018) Denosumab: A Unique Perspective on Adherence and Cost-Effectiveness Compared with Oral Bisphosphonates in Osteoporosis Patients. Annals of Pharmacotherapy, 52, 1031-1041. [Google Scholar] [CrossRef] [PubMed]
[50] Nargesi, S., Barghazan, S.H., Sani’ee, N. and Kemmak, A.R. (2022) Economic Evaluation of Denosumab for Treatment of Postmenopausal Osteoporosis: A Systematic Review. Ira-nian Journal of Public Health, 51, 1502-1512. [Google Scholar] [CrossRef] [PubMed]
[51] Davis, S., Simpson, E., Hamilton, J., et al. (2020) Denosumab, Ra-loxifene, Romosozumab and Teriparatide to Prevent Osteoporotic Fragility Fractures: A Systematic Review and Eco-nomic Evaluation. Health Technology Assessment, 24, 1-314. [Google Scholar] [CrossRef] [PubMed]
[52] Wysham, K.D., Baker, J.F. and Shoback, D.M. (2021) Osteoporosis and Fractures in Rheumatoid Arthritis. Current Opinion in Rheu-matology, 33, 270-276. [Google Scholar] [CrossRef
[53] Shi, M., Chen, L., Wu, H., et al. (2018) Effect of Bisphosphonates on Periprosthetic Bone Loss after Total Knee Arthroplasty: A Meta-Analysis of Ran-domized Controlled Trials. BMC Musculoskeletal Disorders, 19, Article No. 177. [Google Scholar] [CrossRef] [PubMed]
[54] Cohen, J.S., Agarwal, A.R., Kinnard, M.J., Thakkar, S.C. and Golladay, G.J. (2023) The Association of Postoperative Osteoporosis Therapy with Periprosthetic Fracture Risk in Pa-tients Undergoing Arthroplasty for Femoral Neck Fractures. The Journal of Arthroplasty, 38, 726-731. [Google Scholar] [CrossRef] [PubMed]
[55] Xu, J., Li, H., Qu, Y., et al. (2021) Denosumab Might Prevent Periprosthetic Bone Loss after Total Hip and Knee Arthroplasties: A Review. Arthroplasty, 3, Article No. 13. [Google Scholar] [CrossRef] [PubMed]
[56] Porta-Sales, J., Garzón-Rodríguez, C., Llorens-Torromé, S., et al. (2017) Evidence on the Analgesic Role of Bisphosphonates and Denosumab in the Treatment of Pain due to Bone Me-tastases: A Systematic Review within the European Association for Palliative Care Guidelines Project. Palliative Medicine, 31, 5-25. [Google Scholar] [CrossRef] [PubMed]
[57] Nawrat-Szołtysik, A., Miodonska, Z., Piejko, L., et al. (2021) Assessment of Quality of Life and Pain Severity in Older Men with Osteoporosis: Cross-Sectional Study. International Journal of Environmental Research and Public Health, 18, Article No. 11276. [Google Scholar] [CrossRef] [PubMed]
[58] Tetsunaga, T., Tetsunaga, T., Nishida, K., et al. (2017) Denosumab and Alendronate Treatment in Patients with Back Pain Due to Fresh Osteoporotic Vertebral Fractures. Journal of Ortho-paedic Science, 22, 230-236. [Google Scholar] [CrossRef] [PubMed]
[59] Diker-Cohen, T., Rosenberg, D., Avni, T., et al. (2020) Risk for In-fections during Treatment with Denosumab for Osteoporosis: A Systematic Review and Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism, 105, 1641-1658. [Google Scholar] [CrossRef] [PubMed]
[60] Broadwell, A., Chines, A., Ebeling, P.R., et al. (2021) Denosumab Safety and Efficacy among Participants in the Freedom Extension Study with Mild to Moderate Chronic Kidney Disease. The Journal of Clinical Endocrinology & Metabolism, 106, 397-409. [Google Scholar] [CrossRef] [PubMed]
[61] Chandran, T. and Venkatachalam, I. (2019) Efficacy and Safety of Denosumab Compared to Bisphosphonates in Improving Bone Strength in Postmenopausal Osteoporosis: A Systematic Review. Singapore Medical Journal, 60, 364-378. [Google Scholar] [CrossRef] [PubMed]
[62] Kondo, H., Okimoto, N., Yoshioka, T., et al. (2020) Zoledronic Acid Sequential Therapy Could Avoid Disadvantages due to the Discontinuation of Less than 3-Year Denosumab Treatment. Journal of Bone and Mineral Metabolism, 38, 894-902. [Google Scholar] [CrossRef] [PubMed]
[63] Niimi, R., Kono, T., Nishihara, A., et al. (2020) Second Re-bound-Associated Vertebral Fractures after Denosumab Discontinuation. Archives of Osteoporosis, 15, Article No. 7. [Google Scholar] [CrossRef] [PubMed]
[64] 夏维波. 地舒单抗在骨质疏松症临床合理用药的中国专家建议[J]. 中华骨质疏松和骨矿盐疾病杂志, 2020, 13(6): 499-508.
[65] Lee, C.-C., Wang, C.-Y., Hung, C.-C., et al. (2021) A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss after Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial. Frontiers in Medi-cine, 8, Article 717168. [Google Scholar] [CrossRef] [PubMed]
[66] Chandran, M. (2022) The Why and How of Sequential and Combination Therapy in Osteoporosis. A Review of the Current Evidence. Archives of Endocrinology and Metabolism, 66, 724-738. [Google Scholar] [CrossRef] [PubMed]
[67] Kunizawa, K., Hiramatsu, R., Hoshino, J., et al. (2020) Denosumab for Dialysis Patients with Osteoporosis: A Cohort Study. Scientific Reports, 10, Article No. 2496. [Google Scholar] [CrossRef] [PubMed]
[68] Bone, H.G., Wagman, R.B., Brandi, M.L., et al. (2017) 10 Years of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Results from the Phase 3 Randomised FREEDOM Trial and Open-Label Extension. The Lancet Diabetes and Endocrinology, 5, 513-523. [Google Scholar] [CrossRef
[69] Watts, N.B., Grbic, J.T., Binkley, N., et al. (2019) Invasive Oral Procedures and Events in Postmenopausal Women with Osteoporosis Treated with Denosumab for Up to 10 Years. The Journal of Clinical Endocrinology & Metabolism, 104, 2443-2452. [Google Scholar] [CrossRef] [PubMed]