骨吸收
骨吸收(Bone resorption)是指破骨细胞將硬骨组织分解為矿物质的過程[1],此機制會將骨骼中的钙釋放至血液中[2]。
骨吸收 | |
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破骨细胞的光学显微图显示典型的区别特征:具有多个核的大细胞和“泡沫状”胞质溶胶。 | |
分类和外部资源 | |
醫學專科 | 风湿病学 |
ICD-10 | M80 |
eMedicine | 851968 |
破骨细胞是含有大量线粒体和溶酶体的多核细胞,具有分解硬骨的能力。破骨细胞會先附着於骨元上,並將自己附著於硬骨部分的細胞膜折疊起來,製造一個空隙。之後在該空隙中釋放胶原酶和其他在吸收过程中重要的酶。随着破骨细胞隧道进入矿化骨,高水平的钙、镁、磷酸盐和胶原蛋白产物将被释放到细胞外液中。破骨细胞在干癣性关节炎和风湿病中发现的组织破坏中很突出。[3]
人体处于不断的骨重塑状态。[4]骨重塑是通过用新合成的蛋白质基质(Proteinaceous matrix)包替换旧骨的离散部分来维持骨强度和离子稳态的过程。[5]骨被破骨细胞吸收,并由成骨细胞在称为成骨作用的过程中沉积。[6]骨细胞活性在这一过程中起关键作用。导致骨的质量减少的情况可能是由吸收增加或成骨作用减少引起的。在儿童时期,骨形成超过吸收。随着老化过程的发生,吸收超过形成。[5]
由于与更年期相关的雌激素缺乏,绝经后老年妇女的骨吸收率要高得多。[7]常见的治疗方法包括增加骨矿物质密度的药物。双膦酸盐、RANKL抑制剂、SERM(选择性雌激素受体调节剂)、激素替代疗法和降钙素是一些常见的治疗方法。[8]轻量负重运动倾向于消除骨吸收的负面影响。[9]
调节
骨吸收受到来自身体其他部位的信号的高度刺激或抑制,这取决于对钙的需求。
甲状旁腺中的钙敏感膜受体监测细胞外液中的钙水平。低水平的钙会刺激甲状旁腺主细胞释放甲状旁腺激素(PTH)。[4]除了对肾脏和肠道的影响外,PTH还能增加破骨细胞的数量和活性。已经存在的破骨细胞活性的增加是PTH的初始作用,并在几分钟内开始,几个小时内增加。[翻译腔][4]PTH水平的持续升高会增加破骨细胞的丰度。这导致更大的钙和磷酸根离子再吸收。[4]
另一方面,血液中高水平的钙会导致甲状旁腺释放的PTH减少,从而降低破骨细胞的数量和活性,从而减少骨吸收。维生素D增加肠道对钙和磷酸盐的吸收,导致血浆钙水平升高,[4]从而降低骨吸收。
骨化三醇(1,25-二羟基胆钙化醇)是维生素D3的活性形式。[10]它具有许多与血钙水平有关的功能。最近的研究表明,骨化三醇导致破骨细胞形成和骨吸收减少。[11][12]因此,维生素D3摄入量的增加应该会导致骨吸收减少——已经表明,口服维生素D与血清骨化二醇水平的增加没有线性关系,[13]骨化三醇的前体。[請求校對翻譯]
降钙素是人体甲状腺分泌的一种激素。降钙素降低破骨细胞活性,减少新破骨细胞的形成,导致再吸收减少。[4]降钙素对幼儿的影响大于成人,在骨重塑中的作用比PTH小。[4]
在某些骨吸收超过成骨作用的情况下,骨的分解速度远快于它的更新速度。骨头变得更加多孔和脆弱,使人们面临骨折的风险。根据身体骨吸收发生的位置,可能会出现牙齿脱落等其他问题。这可能是由甲状旁腺功能亢进和维生素D缺乏症等疾病引起的,甚至是老年人激素分泌减少引起的。一些具有骨密度降低症状的疾病是骨质疏松症和佝偻病。
一些经历骨吸收增加和骨形成减少的人是宇航员。由于处于零重力环境中,宇航员不需要像在地球上那样使用他们的肌肉骨骼系统[翻译腔]。由于缺乏压力,成骨作用减少,而吸收增加,导致骨密度净减少。[14]
酗酒
酒精对骨密度的影响是众所周知的,并且在动物和人群中进行了充分研究。通过直接和间接途径,长期接触乙醇会降低骨矿物质密度和促进骨质疏松症,从而增加骨折风险。过度饮酒的间接影响通过生长激素、性类固醇和氧化应激发生。
生长激素是成人骨骼生长和重塑的重要调节剂,它通过胰岛素样生长因子1(IGF1)刺激成骨细胞分化。[15]慢性酒精中毒会降低IGF1的水平,从而抑制生长激素增加骨密度的能力。[15]
饮酒量的增加与睾酮和血清雌二醇水平的降低有关,这反过来会导致促进破骨细胞形成的NF-κB受体激活剂(RANK,一种TNF受体)蛋白的激活。[16]当乙醇诱导NADPH氧化酶表达时会产生氧化应激,导致成骨细胞产生活性氧类,最终导致细胞衰老。[17]慢性酒精中毒的直接影响在成骨细胞、破骨细胞和骨细胞中很明显。乙醇抑制成骨细胞的活性和分化。
同时,它对破骨细胞的活性有直接影响。由于骨中凹坑数量和凹坑面积的增加,导致骨吸收率增加和骨密度降低。[18][19][20]研究表明,有活力的骨细胞(另一种类型的骨细胞)可以阻止破骨细胞的生成,而凋亡的骨细胞倾向于诱导破骨细胞刺激。酒精暴露刺激骨细胞凋亡可以解释长期饮酒者骨密度降低的原因。[20][21]
参见
参考文献
- ^ 醫學主題詞表(MeSH):Bone+Resorption
- ^ Teitelbaum SL. Bone resorption by osteoclasts.. Science. 2000, 289 (5484): 1504–8. Bibcode:2000Sci...289.1504T. PMID 10968780. doi:10.1126/science.289.5484.1504.
- ^ Mensah, Kofi A.; Schwarz, Edward M.; Ritchlin, Christopher T. Altered Bone Remodeling in Psoriatic Arthritis. Current Rheumatology Reports. 2008-08-01, 10 (4): 311–317. ISSN 1523-3774. PMC 2656567 . PMID 18662512. doi:10.1007/s11926-008-0050-5.
- ^ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Guyton and Hall Textbook of Medical Physiology, 12th Edition. ISBN 1416045740
- ^ 5.0 5.1 Clarke, Bart. Normal Bone Anatomy and Physiology. Clinical Journal of the American Society of Nephrology. 2008-11-01, 3 (Suppl 3): S131–S139. ISSN 1555-9041. PMC 3152283 . PMID 18988698. doi:10.2215/CJN.04151206.
- ^ Maurel, D. B.; Jaffre, C.; Rochefort, G. Y.; Aveline, P. C.; Boisseau, N.; Uzbekov, R.; Gosset, D.; Pichon, C.; Fazzalari, N. L. Low bone accrual is associated with osteocyte apoptosis in alcohol-induced osteopenia. Bone. 2011-09-01, 49 (3): 543–552. ISSN 1873-2763. PMID 21689804. doi:10.1016/j.bone.2011.06.001.
- ^ Feng, Xu; McDonald, Jay M. Disorders of Bone Remodeling. Annual Review of Pathology. 2011-01-01, 6: 121–145. ISSN 1553-4006. PMC 3571087 . PMID 20936937. doi:10.1146/annurev-pathol-011110-130203.
- ^ Russell, G.; Mueller, G.; Shipman, C.; Croucher, P. Clinical disorders of bone resorption. Novartis Foundation Symposium. Novartis Foundation Symposia. 2001-01-01, 232: 251–267; discussion 267–271. ISBN 9780471494331. ISSN 1528-2511. PMID 11277085. doi:10.1002/0470846658.ch17.
- ^ Shanb, Alsayed A.; Youssef, Enas F. The impact of adding weight-bearing exercise versus nonweight bearing programs to the medical treatment of elderly patients with osteoporosis. Journal of Family and Community Medicine. 2014-01-01, 21 (3): 176–181. ISSN 1319-1683. PMC 4214007 . PMID 25374469. doi:10.4103/2230-8229.142972.
- ^ Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. 3, Overview of Vitamin D. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56061/ (页面存档备份,存于互联网档案馆)
- ^ Kikuta J, Kawamura S, Okiji F, Shirazaki M, Sakai S, Saito H, Ishii M. Sphingosine-1-phosphate-mediated osteoclast precursor monocyte migration is a critical point of control in antibone-resorptive action of active vitamin D.. Proceedings of the National Academy of Sciences of the United States of America. Apr 2013, 110 (17): 7009–13. Bibcode:2013PNAS..110.7009K. PMC 3637769 . PMID 23569273. doi:10.1073/pnas.1218799110 .
- ^ Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Nakamichi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y. Vitamin D receptor in osteoblasts is a negative regulator of bone mass control. Endocrinology. Mar 2013, 154 (3): 1008–20. PMID 23389957. doi:10.1210/en.2012-1542 .
- ^ Stamp TC, Haddad JG, Twigg CA. Comparison of oral 25-hydroxycholecalciferol, vitamin D, and ultraviolet light as determinants of circulating 25-hydroxyvitamin D.. The Lancet. Jun 1977, 1 (8026): 1341–3. PMID 69059. S2CID 9326591. doi:10.1016/s0140-6736(77)92553-3.
- ^ Iwamoto J, Takeda T, Sato Y. Interventions to prevent bone loss in astronauts during space flight. The Keio Journal of Medicine. Jun 2005, 54 (2): 55–9. PMID 16077253. doi:10.2302/kjm.54.55 .
- ^ 15.0 15.1 Maddalozzo, G. F.; Turner, R. T.; Edwards, C. H. T.; Howe, K. S.; Widrick, J. J.; Rosen, C. J.; Iwaniec, U. T. Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporosis International. 2009-09-01, 20 (9): 1529–1538. ISSN 1433-2965. PMID 19238309. S2CID 11502836. doi:10.1007/s00198-009-0836-y.
- ^ Ronis, Martin J. J.; Wands, Jack R.; Badger, Thomas M.; de la Monte, Suzanne M.; Lang, Charles H.; Calissendorff, Jan. Alcohol-induced disruption of endocrine signaling. Alcoholism: Clinical and Experimental Research. 2007-08-01, 31 (8): 1269–1285. ISSN 0145-6008. PMID 17559547. doi:10.1111/j.1530-0277.2007.00436.x.
- ^ Chen, Jin-Ran; Shankar, Kartik; Nagarajan, Shanmugam; Badger, Thomas M.; Ronis, Martin J. J. Protective effects of estradiol on ethanol-induced bone loss involve inhibition of reactive oxygen species generation in osteoblasts and downstream activation of the extracellular signal-regulated kinase/signal transducer and activator of transcription 3/receptor activator of nuclear factor-kappaB ligand signaling cascade. The Journal of Pharmacology and Experimental Therapeutics. 2008-01-01, 324 (1): 50–59. ISSN 1521-0103. PMID 17916759. S2CID 27152788. doi:10.1124/jpet.107.130351.
- ^ Robling, Alexander G.; Bonewald, Lynda F. The Osteocyte: New Insights. Annual Review of Physiology. 10 February 2020, 82 (1): 485–506 [8 March 2022]. ISSN 0066-4278. PMC 8274561 . PMID 32040934. doi:10.1146/annurev-physiol-021119-034332.
- ^ Bonewald, Lynda F. The amazing osteocyte. Journal of Bone and Mineral Research. 2011-02-01, 26 (2): 229–238. ISSN 1523-4681. PMC 3179345 . PMID 21254230. doi:10.1002/jbmr.320.
- ^ 20.0 20.1 Verborgt, Olivier; Tatton, Nadine A.; Majeska, Robert J.; Schaffler, Mitchell B. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation?. Journal of Bone and Mineral Research. 2002-05-01, 17 (5): 907–914. ISSN 0884-0431. PMID 12009022. S2CID 22428635. doi:10.1359/jbmr.2002.17.5.907. hdl:10067/1033580151162165141 .
- ^ Maurel DB, Jaffre C, Rochefort GY, Aveline PC, Boisseau N, Uzbekov R, Gosset D, Pichon C, Fazzalari NL, Pallu S, Benhamou CL. Low bone accrual is associated with osteocyte apoptosis in alcohol-induced osteopenia. Bone. September 2011, 49 (3): 543–52. PMID 21689804. doi:10.1016/j.bone.2011.06.001.