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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (6): 10-14.doi: 10.6040/j.issn.1671-7554.0.2021.0324

• 骨质疏松症新进展专题 • 上一篇    下一篇

骨质疏松的病因及发病机制研究进展

罗湘杭,周若玙   

  1. 中南大学湘雅医院内分泌科/内分泌研究中心, 湖南 长沙 410008
  • 发布日期:2021-06-10
  • 通讯作者: 罗湘杭. E-mail:xianghangluo@hotmail.com

Advances on the etiology and pathogenesis of osteoporosis

LUO Xianghang, ZHOU Ruoyu   

  1. Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha 410008, Hunan, China
  • Published:2021-06-10

摘要: 骨质疏松是最常见的代谢性骨病。随着年龄的增长,骨质疏松症的发病率逐渐上升,合并骨折的发生率也随之增加,对患者的健康造成严重的伤害。因此找到骨质疏松的有效治疗方法十分必要。骨质疏松的核心发病机制是各种致病因素作用于骨形成或重建的某一个或多个阶段,最终导致的骨吸收大于骨形成。这些原因包括遗传背景、年龄、内分泌环境以及生活方式等。研究骨质疏松症的发病机制与病因对其预防与治疗有很大的帮助。

关键词: 骨质疏松, 病因, 发病机制, 衰老

Abstract: Osteoporosis is the most common metabolic bone disease. The incidence of osteoporosis as well as osteoporotic fracture increases gradually with age, seriously endangering patients health. The core pathogenesis of osteoporosis is that various factors act on some stages of bone remodeling, resulting in stronger bone resorption than bone formation. These factors include genetic factors, age, endocrine and lifestyle. It is of great significance to study the pathogenesis and etiology of osteoporosis for its prevention and treatment.

Key words: Osteoporosis, Etiology, Pathogenesis, Aging

中图分类号: 

  • R580
[1] Qaseem A, Forciea MA, McLean RM, et al. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians [J]. Ann Intern Med, 2017, 166(11): 818-839.
[2] Feng X, McDonald JM. Disorders of bone remodeling [J]. Annu Rev Pathol, 2011, 6: 121-145. doi:10.1146/annure-pathol-011110-130203.
[3] Kruse HP, Kuhlencordt F. Pathogenesis and natural course of primary osteoporosis [J]. Lancet, 1980, 1(8163): 280-282.
[4] Walker-Bone K. Recognizing and treating secondary osteoporosis [J]. Nat Rev Rheumatol, 2012, 8(8): 480-492.
[5] Hadjidakis DJ, Androulakis. Bone remodeling [J]. Ann N Y Acad Sci, 2006, 1092: 385-396. doi: 10.1196/annals.1365.035.
[6] Karsenty G. The central regulation of bone remodeling [J]. Trends Endocrinol Metab, 2000, 11(10): 437-439.
[7] Zhang L, Su P, Xu C, et al. Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARγ expression and enhancing Runx2 expression [J]. J Pineal Res, 2010, 49(4): 364-372.
[8] Li CJ, Xiao Y, Yang M, et al. Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging [J]. J Clin Invest, 2018, 128(12): 5251-5266.
[9] Ortinau LC, Wang H, Lei K, et al. Identification of functionally distinct Mx1+αSMA+ periosteal skeletal stem cells [J]. Cell Stem Cell, 2019, 25(6): 784-796.e785.
[10] Debnath S, Yallowitz AR, McCormick J, et al. Discovery of a periosteal stem cell mediating intramembranous bone formation [J]. Nature, 2018, 562(7725): 133-139.
[11] Han Y, You X, Xing W, et al. Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts [J]. Bone Res, 2018, 6: 16. doi: 10.1038/s41413-018-0019-6. eCollection 2018.
[12] Al Rifai O, Chow J, Lacombe J, et al. Proprotein convertase furin regulates osteocalcin and bone endocrine function [J]. J Clin Invest, 2017, 127(11): 4104-4117.
[13] Wu M, Chen G, Li YP. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease [J]. Bone Res, 2016, 4: 16009. doi:10.1038/boneres.2016.9.
[14] McGregor NE, Murat M, Elango J, et al. IL-6 exhibits both cis- and trans-signaling in osteocytes and osteoblasts, but only trans-signaling promotes bone formation and osteoclastogenesis [J]. J Biol Chem, 2019, 294(19): 7850-7863.
[15] 张猛, 牛泽锋, 王翠杰, 等. 破骨细胞活性及其调节因子的研究进展[J]. 脊柱外科杂志, 2018, 16(3): 179-182. ZHANG Meng, NIU Zefeng, WANG Cuijie, et al. Research progress of osteoclast activity and its regulating factors [J]. Journal of Spinal Surgery, 2018, 16(3): 179-182.
[16] Maré A, DHaese PC, Verhulst A. The role of sclerostin in bone and ectopic calcification [J]. Int J Mol Sci, 2020, 21(9): 3199. doi: 10.3390/ijms21093199.
[17] Bullock WA, Hoggatt AM, Horan DJ, et al. Lrp4 mediates bone homeostasis and mechanotransduction through interaction with sclerostin in vivo [J]. iScience, 2019, 20: 205-215. doi: 10.1016/j.isci.2019.09.023.
[18] Liu W, Wang Z, Yang J, et al. Osteocyte TSC1 promotes sclerostin secretion to restrain osteogenesis in mice [J]. Open Biol, 2019, 9(5): 180262. doi: 10.1098/rsob.180262.
[19] Fijalkowski I, Geets E, Steenackers E, et al. A novel domain-specific mutation in a sclerosteosis patient suggests a role of LRP4 as an anchor for sclerostin in human bone [J]. J Bone Miner Res, 2016, 31(4): 874-881.
[20] Delgado-Calle J, Sato AY, Bellido T, Role and mechanism of action of sclerostin in bone [J]. Bone, 2017, 96: 29-37. doi: 10.1016/j.bone.2016.10.007.
[21] Morgan EF, Unnikrisnan GU, Hussein AI. Bone mechanical properties in healthy and diseased states [J]. Annu Rev Biomed Eng, 2018, 20: 119-143. doi: 10.1146/annurev-bioeng-062117-121139.
[22] Lee WC, Guntur AR, Long F, et al. Energy metabolism of the osteoblast: implications for osteoporosis [J]. Endocr Rev, 2017, 38(3): 255-266.
[23] Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone [J]. Nature, 2014, 507(7492): 323-328.
[24] Yang M, Li CJ, Xiao Y, et al. Ophiopogonin D promotes bone regeneration by stimulating CD31(hi)EMCN(hi)vessel formation [J]. Cell Prolif, 2020, 53(3): e12784. doi: 10.1111/cpr.12784.
[25] Yang M, Li CJ, Sun X, et al. MiR-497-195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity [J]. Nat Commun, 2017, 8: 16003. doi: 10.1038/ncomms16003.
[26] Ralston SH, Uitterlinden AG. Genetics of osteoporosis [J]. Endocr Rev, 2010, 31(5): 629-662.
[27] Zhang L, Yin X, Wang J, et al. Associations between VDR gene polymorphisms and osteoporosis risk and bone mineral density in postmenopausal women: a systematic review and Meta-analysis [J]. Sci Rep, 2018, 8(1): 981.
[28] 赵航, 马慧娟, 王超. 骨质疏松症相关基因研究进展[J]. 实用老年医学, 2019, 33(6): 9-13.
[29] Zhu X, Zheng H, Factors influencing peak bone mass gain [J]. Front Med, 2021, 15(1): 53-69.
[30] Windahl SH, Börjesson AE, Farman HH, et al. Estrogen receptor-α in osteocytes is important for trabecular bone formation in male mice [J]. Proc Natl Acad Sci U S A, 2013, 110(6): 2294-2299.
[31] Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton [J]. Trends Endocrinol Metab, 2012, 23(11): 576-581.
[32] Nakamura T, Imai Y, Matsumoto T, et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts [J]. Cell, 2007, 130(5): 811-823.
[33] Almeida M, Laurent MR, Dubois V, et al. Estrogens and androgens in skeletal physiology and pathophysiology [J]. Physiol Rev, 2017, 97(1): 135-187.
[34] Li CJ, Cheng P, Liang MK, et al. MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation [J]. J Clin Invest, 2015, 125(4): 1509-1522.
[35] 王洪复, 于明香. 老年人成骨细胞骨形成功能的衰退与治疗[J]. 国外医学(内分泌学分册), 2003, 23(2): 79-80,97.
[36] Hemmatian H, Bakker AD, Klein-Nulend J, et al. Aging, osteocytes, and mechanotransduction [J]. Curr Osteoporos Rep, 2017, 15(5): 401-411.
[37] Cai D, Khor S. “Hypothalamic Microinflammation” Paradigm in Aging and Metabolic Diseases [J]. Cell Metab, 2019, 30(1): 19-35.
[38] Zhang G, Li J, Purkayastha S, et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH [J]. Nature, 2013, 497(7448): 211-216.
[39] Xiao YZ, Yang M, Xiao Y, et al. Reducing hypothalamic stem cell senescence protects against aging-associated physiological decline [J]. Cell Metab, 2020, 31(3): 534-548.e535.
[40] Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal andextraskeletal actions of Vitamin D: current evidence and outstanding questions [J]. Endocr Rev, 2019, 40(4): 1109-1151.
[41] Polzonetti V, Pucciarelli S, Vincenzetti S, et al. Dietary intake of Vitamin D from dairy products reduces the risk of osteoporosis [J]. Nutrients, 2020, 12(6): 1743. doi: 10.3390/nu12061743.
[42] Hardcastle SA, Yahya F, Bhalla AK. Pregnancy-associated osteoporosis: a UK case series and literature review [J]. Osteoporos Int, 2019, 30(5): 939-948.
[43] Papageorgiou M, Sathyapalan T, Schutte R. Muscle mass measures and incident osteoporosis in a large cohort of postmenopausal women [J]. J Cachexia Sarcopenia Muscle, 2019, 10(1): 131-139.
[44] Li G, Zhang L, Wang D, et al. Muscle-bone crosstalk and potential therapies for sarco-osteoporosis [J]. J Cell Biochem, 2019, 120(9): 14262-14273.
[45] McDonald MM, Khoo WH, Ng PY, et al. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption [J]. Cell, 2021, 184(5): 1330-1347.
[46] Fabre S, Funck-Brentano T, Cohen-Solal M. Anti-sclerostin antibodies in osteoporosis and other bone diseases [J]. J Clin Med, 2020, 9(11):3439. doi: 10.3390/jcm9113439.
[47] Asadipooya K, Weinstock A. Cardiovascular outcomes of romosozumab and protective role of alendronate [J]. Arterioscler Thromb Vasc Biol, 2019, 39(7): 1343-1350.
[48] Ardura JA, Portal-Núñez S, Alonso V, et al. Handling parathormone receptor type 1 in skeletal diseases: realities and expectations of abaloparatide [J]. Trends Endocrinol Metab, 2019, 30(10): 756-766.
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