• 1:中华医学会骨质疏松和骨矿盐疾病分会

摘要(Abstract)：

<正>自20世纪初对佝偻病的研究发现维生素D以来,维生素D与钙磷代谢和骨骼健康的重要关联被不断发现。我国内分泌学先驱刘士豪教授和朱宪彝教授针对维生素D与钙磷代谢和骨软化的研究,以及由他们提出并命名的"肾性骨营养不良"得到了国际学者的广

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参考文献(References)：

• [1]周学瀛,夏维波.维生素D到底是什么?[J].中华骨质疏松和骨矿盐疾病杂志,2015,8:90-92.
• [2]Bikle D.Nonclassic actions of vitamin D[J].J Clin Endocrinol Metab,2009,94:26-34.
• [3]Holick MF.The Vitamin D solution:a 3-step strategy to cure our most common health problems[M].New York:Plume,2011.
• [4]Holick MF,Chen TC.Vitamin D deficiency:a worldwide problem with health consequences[J].Am J Clin Nutr,2008,87:1080S-1086S.
• [5]Chen J,Yun C,He Y,et al.Vitamin D status among the elderly Chinese population:a cross-sectional analysis of the2010-2013 China National Nutrition and Health Survey(CNNHS)[J].Nutr J,2017,16:3.
• [6]Li M,Lv F,Zhang Z,et al.Establishment of a normal reference value of parathyroid hormone in a large healthy Chinese population and evaluation of its relation to bone turnover and bone mineral density[J].Osteoporos Int,2016,27:1907-1916.
• [7]Holick MF.Vitamin D deficiency[J].N Engl J Med,2007,357:266-281.
• [8]Haddad JG,Matsuoka LY,Hollis BW,et al.Human plasma transport of vitamin D after its endogenous synthesis[J].J Clin Invest,1993,91:2552-2555.
• [9]De Luca HF.Overview of general physiologic features and functions of vitamin D[J].Am J Clin Nutr,2004,80:1689S-1696S.
• [10]Bikle DD,Gee E,Halloran B,et al.Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein[J].J Clin Endocrinol Metab,1986,63:954-959.
• [11]Christakos S,Dhawan P,Liu Y,et al.New insights into the mechanisms of vitamin D action[J].J Cell Biochem,2003,88:695-705.
• [12]Eisman JA,Bouillon R.Vitamin D:direct effects of vitamin D metabolites on bone:lessons from genetic-ally modified mice[J].Bonekey Rep,2014,3:499.
• [13]Adams JS,Hewison M.Update in vitamin D[J].J Clin Endocrinol Metab,2010,95:471-478.
• [14]Liu PT,Stenger S,Li H,et al.Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response[J].Science,2006,311:1770-1773.
• [15]Bouillon R,Bischoff-Ferrari H,Willett W.Vitamin D and health:perspectives from mice and man[J].J Bone Miner Res,2008,23:974-979.
• [16]Xie Z,Munson SJ,Huang N,et al.The mechanism of 1,25-dihydroxyvitamin D(3)autoregulation in keratinocytes[J].J Biol Chem,2002,277:36987-36990.
• [17]Holick MF,Binkley NC,Bischoff-Ferrari HA,et al.Evaluation,treatment,and prevention of vitamin D deficiency:an endocrine society clinical practice guideline[J].J Clin Endocrinol Metab,2011,96:1911-1930.
• [18]van Schoor N,Lips P.Global overview of vitamin D status[J].Endocrinol Metab Clin North Am,2017,46:845-870.
• [19]Hu Y,Chen J,Wang R,et al.Vitamin D nutritional status and its related factors for Chinese Children and Adolescents in2010-2012[J].Nutrients,2017,9:1024.
• [20]Ning Z,Song S,Miao L,et al.High prevalence of vitamin D deficiency in urban health checkup population[J].Clin Nutr,2016,35:859-863.
• [21]Man PW,van der Meer IM,Lips P,et al.Vitamin D status and bone mineral density in the Chinese population:a review[J].Arch Osteoporos,2016,11:14.
• [22]Lu H,Zhang Z,Ke Y,et al.High prevalence of vitamin D insufficiency in China:relationship with the levels of parathyroid hormone and markers of bone turnover[J].PLo S One2012,7:e47264.
• [23]Zhen D,Liu L,Guan C,et al.High prevalence of vitamin D deficiency among middle-aged and elderly individuals in northwestern China:its relationship to osteoporosis and lifestyle factors[J].Bone,2015,71:1-6.
• [24]Vieth R,Ladak Y,Walfish PG.Age-related changes in the25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D[J].J Clin Endocrinol Metab,2003,88:185-191.
• [25]Touvier M,Deschasaux M,Montourcy M,et al.Determinants of vitamin D status in Caucasian adults:influ-ence of sun exposure,dietary intake,sociodemographic,lifestyle,anthropometric,and genetic factors[J].J Invest Dermatol,2015,135:378-388.
• [26]Clemens TL,Adams JS,Henderson SL,et al.Increased skin pigment reduces the capacity of skin to synthesis vitamin D3[J].Lancet,1982,1:74-76.
• [27]Grigalavicius M,Juzeniene A,Baturaite Z,et al.Biologically efficient solar radiation:Vitamin D produc-tion and induction of cutaneous malignant melanoma[J].Dermatoendocrinology,2013,5:150-158.
• [28]Holick MF,Chen TC,Lu Z,et al.Vitamin D and skinphysiology:a D-lightful story[J].J Bone Miner Res,2007,22:28-33.
• [29]Buyukuslu N,Esin K,Hizli H,et al.Clothing preference affects vitamin D status of young women[J].Nutr Res,2014,34:688-693.
• [30]Tsur A,Metzger M,Dresner-Pollak R.Effect of different dress style on vitamin D level in healthy young Orthodox and ultra-Orthodox students in Israel[J].Osteoporos Int,2011,22:2895-2898.
• [31]Matsuoka LY,Ide L,Wortsman J,et al.Sunscreens suppress cutaneous vitamin D3synthesis[J].J Clin Endocrinol Metab,1987,64:1165-1168.
• [32]Agarwal KS,Mughal MZ,Upadhyay P,et al.The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi[J].India Arch Dis Child,2002,87:111-113.
• [33]Chen J,Yun C,He Y,et al.Vitamin D status among the elderly Chinese population:a cross-sec-tional analysis of the2010-2013 China national nutrition and health survey(CNNHS)[J].Nutr J,2017,16:3.
• [34]Manicourt DH,Devogelaer JP.Urban tropospheric ozone increases the prevalence of vitamin D deficiency among Belgian postmenopausal women with outdoor activities during summer[J].J Clin Endocrinol Metab,2008,93:3893-3899.
• [35]Feizabad E,Hossein-Nezhad A,Maghbooli Z,et al.Impact of air pollution on vitamin D deficiency and bone health in adolescents[J].Arch Osteoporos.2017,12:34.
• [36]Hosseinpanah F,Pour SH,Heibatollahi M,et al.The effects of air pollution on vitamin D status in healthy women:a cross sectional study[J].BMC Public Health,2010,10:519.
• [37]Kelishadi R,Moeini R,Poursafa P,et al.In-dependent association between air pollutants and vitamin D deficiency in young children in Isfahan,Iran[J].Paediatr Int Child Health,2014,34:50-55.
• [38]Ba6z N,Dargent-Molina P,Wark JD,et al.Gestational exposure to urban air pollution related to a decrease in cord blood vitamin d levels[J].J Clin Endocrinol Metab,2012,97:4087-4095.
• [39]Leary PF,Zamfirova I,Au J,et al.Effect of Latitude on Vitamin D Levels[J].J Am Osteopath Assoc,2017,117:433-439.
• [40]Leung C,Warner J,Harris M,et al.Symptomatic Hypocalcemia Secondary to Rifampicin-induced Hypovitaminosis D[J].Pediatr Infect Dis J,2016,35:822-823.
• [41]Hunter D,De Lange M,Snieder H,et al.Genetic contribution to bone metabolism,calcium excretion,and vitamin D and parathyroid hormone regulation[J].J Bone Miner Res,2001,16:371-378.
• [42]Shea MK,Benjamin EJ,Dupuis J,et al.Genetic and nongenetic correlates of vitamins K and D[J].Eur J Clin Nutr,2009,63:458-464.
• [43]Wjst M,Altmüller J,Braig C,et al.A genome-wide linkage scan for 25-OH-D(3)and 1,25-(OH)2-D3serum levels in asthma families[J].J Steroid Biochem Mol Biol,2007,103:799-802.
• [44]Wang TJ,Zhang F,Richards JB,et al.Common genetic determinants of vitamin D insufficiency:a genome-wide association study[J].Lancet,2010,376:180-188.
• [45]Nissen J,Vogel U,Ravn-Haren G,et al.Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D3-fortified bread and milk during winter in Denmark[J].Am J Clin Nutr,2015,101:218-227.
• [46]Ordó1z-Mena JM,Maalmi H,Sch9ttker B,et al.Genetic variants in the vitamin D pathway,25(OH)D Levels,and mortality in a large population-based cohort study[J].J Clin Endocrinol Metab,2017,102:470-477.
• [47]Zhang Z,He JW,Fu WZ,et al.An analysis of the association between the vitamin D pathway and serum 25-hydroxyvitamin D levels in a healthy Chinese population[J].J Bone Miner Res,2013,28:1784-1792.
• [48]Li SS,Gao LH,Zhang XY,et al.Genetically low vitamin d levels,bone mineral density,and bone metabolism markers:a Mendelian Randomisation study[J].Sci Rep,2016,6:33202.
• [49]Thacher TD,Fischer PR,Pettifor JM.Rickets:vitamin D and calcium deficiency[J].J Bone Miner Res,2007,22:638.
• [50]Shaw NJ,Mughal MZ.Vitamin D and child health Part 1(skeletal aspects)[J].Arch Dis Child,2013,98:363-367.
• [51]孟迅吾.骨软化症和佝偻病[M]//史轶蘩.协和内分泌代谢学.北京:科学出版社,1999:1529-1542.
• [52]Lieben L,Masuyama R,Torrekens S,et al.Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization[J].J Clin Invest,2012,122:1803-1815.
• [53]Tiosano D,Hochberg Z.Hypophosphatemia:the common denominator of all rickets[J].J Bone Miner Metab,2009,27:392-401.
• [54]Kim CJ,Kaplan LE,Perwad F,et al.Vitamin D 1alphahy-droxylase gene mutations in patients with 1alpha-hydroxylase deficiency[J].J Clin Endocrinol Metab,2007,92:3177-3182.
• [55]Cui N,Xia W,Su H,et al.Novel mutations of CYP27B1gene lead to reduced activity of 1α-hydroxylase in Chinese patients[J].Bone,2012,51:563-569.
• [56]Thacher TD,Fischer PR,Singh RJ,et al.CYP2R1 Mutations Impair Generation of 25-hydroxyvitamin D and Cause an Atypical Form of Vitamin D Deficiency[J].J Clin Endocrinol Metab,2015,100:E1005-E1013.
• [57]Pang Q,Qi X,Jiang Y,et al.Clinical and genetic findings in a Chinese family with VDR-associated hereditary vitamin D-resistant rickets[J].Bone Res,2016,4:16018.
• [58]Huang XL,Jiang Y,Xia WB.FGF23 and Phosphate Wasting Disorders[J].Bone Res,2013,2:120-132.
• [59]Jiang Y,Xia WB,Xing XP,et al.Tumor-induced osteomalacia:an important cause of adult-onset hypophosphatemic osteomalacia in China:Report of 39 cases and review of the literature[J].J Bone Miner Res,2012,27:1967-1975.
• [60]中华医学会骨质疏松和骨矿盐疾病分会.原发性骨质疏松症诊疗指南[J].中华骨质疏松和骨矿盐疾病杂志,2017,10:413-444.
• [61]WHO.Facts about ageing[EB/OL].[2018-02-04].http://www.who.int/ageing/about/facts/en/indexhtml.
• [62]Chen W,Simpson JM,March LM,et al.Co-morbidities only account for a small proportion of excess mortality after fracture:a record linkage study of individual fracture types[J].J Bone Miner Res,2018.doi:10.1002/jbmr.3374.[Epub ahead of print].
• [63]Cruz-Jentoft AJ,Baeyens JP,Bauer JM,et al.Sarcopenia:European consensus on definition and diagnosis:Report of the European Working Group on sarcopenia in older people[J].Age Ageing,2010,39:412-423.
• [64]Haussler MR,Whitfield GK,Kaneko I,et al.Molecular mechanisms of vitamin D action[J].Calcif Tissue Int,2013,92:77-98.
• [65]Olsson K,Saini A,Str9mberg A,et al.Evidence for vitamin D receptor expression and direct effects of 1α,25(OH)2D3in human skeletal muscle precursor cells[J].Endocrinology,2016,157:98-111.
• [66]Kotlarczyk MP,Perera S,Ferchak MA,et al.Vitamin Ddeficiencyis associated with functional decline and falls in frail elderly women despite supplementation[J].Osteoporos Int,2017,28:1347-1353.
• [67]Weaver CM,Gordon CM,Janz KF,et al.The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors:a systematic review and implementation recommendations[J].Osteoporos Int,2016,27:1281-1386.
• [68]Seamans KM,Hill TR,Scully L,et al.Vitamin d status and indices of bone turnover in older European adults[J].Int J Vitam Nutr Res,2011,81:277-285.
• [69]Kruger MC,Kruger IM,Wentzel-Viljoen E,et al.Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status,low calcium intake,and high bone turnover[J].Nutr Res,2011,31:748-758.
• [70]Ebeling PR.Vitamin D and bone health:epidemiologic studies[J].Bonekey Rep,2014,3:511.
• [71]Reid IR,Bolland MJ,Grey A.Effects of vitamin D supplements on bone mineral density:a systematic review and metaanalysis[J].Lancet,2014,11,383:146-155.
• [72]Dawson-Hughes B,Mithal A,Bonjour JP,et al.IOF position statement:vitamin D recommendations for older adults[J].Osteoporos Int,2010,21:1151-1154.
• [73]Bischoff-Ferrari HA,Dawson-Hughes B,Willett WC,et al.Effect of Vitamin D on falls:a meta-analysis[J].JAMA,2004,291:1999-2006.
• [74]Bischoff-Ferrari HA,Dawson-Hughes B,Staehelin HB,et al.Fall prevention with supplemental and active forms of vitamin D:a meta-analysis of rando-mised controlled trials[J].BMJ,2009,339:b3692.
• [75]Chung M,Lee J,Terasawa T,et al.Vitamin D with or without calcium supplementation for prevention of cancer and fractures:an updated meta-analysis for the U.S.Preventive Services Task Force[J].Ann Intern Med,2011,155:827-838.
• [76]Bischoff-Ferrari HA,Orav EJ,Dawson-Hughes B.Effect of cholecalciferol plus calcium on falling in ambulatory older men and women:a 3-year randomized controlled trial[J].Arch Intern Med,2006,166:424-430.
• [77]O'Donnell S,Moher D,Thomas K,et al.Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls[J].J Bone Miner Metab,2008,26:531-542.
• [78]Liao RX,Yu M,Jiang Y,et al.Management of osteoporosis with calcitriol in elderly Chinese patients:a systematic review[J].Clin Interv Aging,2014,28,9:515-526.
• [79]Zhang ZL,Liao EY,Xia WB,et al.Alendronate sodium/vitamin D3combination tablet versus calcitriol for osteoporosis in Chinesepostmenopausal women:a 6-month,randomized,open-label,active-comparator-controlled study with a 6-monthextension[J].Osteoporos Int,2015,26:2365-2374.
• [80]Pittas AG,Sun Q,Manson JE,et al.Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women[J].Diabetes Care,2010,33:2021-2023.
• [81]Forouhi NG,Ye Z,Rickard AP,et al.Circulating 25-hydroxyvitamin D concentration and the risk of type 2diabetes:results from the European Prospective Investigation into Cancer(EPIC)-Norfolk cohort and updated metaanalysis of prospective studies[J].Diabetologia,2012,55:2173-2182.
• [82]Takiishi T,Gysemans C,Bouillon R,et al.Vitamin D and diabetes[J].Rheum Dis Clin North Am,2012,38:179-206.
• [83]Palomer X,Gonzalez-Clemente JM,Blanco-Vaca F,et al.Role of vitamin D in the pathogenesis of type 2 diabetes mellitus[J].Diabetes Obes Metab,2008,10:185-197.
• [84]Flores M.A role of vitamin D in low-intensity chronic inflammation and insulin resistance in type 2 diabetes mellitus?[J].Nutr Res Rev,2005,18:175-182.
• [85]Martini LA,Wood RJ.Vitamin D status and the metabolic syndrome[J].Nutr Rev,2006,64:479-486.
• [86]Mirhosseini N,Vatanparast H,Mazidi M,et al.The effect of improved serum 25-hydroxyvitamin D status on glycemic control in diabetic patients:A meta-analysis[J].J Clin Endocrinol Metab,2017,102:3097-3110.
• [87]Gagnon C,Lu ZX,Magliano DJ,et al.Serum 25-hydroxyvitamin D,calcium intake,and risk of type 2diabetes after 5 years:results from a national,populationbased prospective study(the Australian Diabetes,Obesity and Lifestyle study)[J].Diabetes Care,2011,34:1133-1138.
• [88]Mitri J,Muraru MD,Pittas AG.Vitamin D and type 2 diabetes:a systematic review[J].Eur J Clin Nutr,2011,65:1005-1015.
• [89]Luo BA,Gao F,Qin LL.The association between Vitamin D deficiency and diabetic retinopathy in type 2 diabetes:A meta-analysis of observational studies[J].Nutrients,2017,20:307.
• [90]de Boer IH,Tinker LF,Connelly S,et al.Women's Health Initiative Investigators.Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women's Health Initiative[J].Diabetes Care,2008,31:701-707.
• [91]Davidson MB,Duran P,Lee ML,et al.High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D[J].Diabetes Care,2013,36:260-266.
• [92]Jorde R,Sollid ST,Svartberg J,et al.Vitamin D 20,000IU per week for five years does not prevent progression from prediabetes to diabetes[J].J Clin Endocrinol Metab,2016,101:1647-1655.
• [93]Zostautiene I,Jorde R,Schirmer H,et al.Genetic variations in the vitamin D receptor predict type 2 diabetes and myocardial infarction in a community-based population:The Troms Study[J].PLo S One,2015,10:e0145359.
• [94]Li L,Wu B,Liu JY,et al.Vitamin D receptor gene polymorphisms and type 2 diabetes:a meta-analysis[J].Archives Med Res,2013,44:235-241.
• [95]Pilz S,Kienreich K,Rutters F,et al.Role of vitamin D in the development of insulin resistance and type 2 diabetes[J].Curr Diab Rep,2013,13:261-270.
• [96]Norman AW.Minireview:vitamin D receptor:new assignments for an already busy receptor[J].Endocrinology,2006,147:5542-5548.
• [97]Maestro B,Campion J,Dvila N,et al.Stimulation by 1,25-dihydroxyvitamin D3of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells[J].Endocr J,2000,47:383-391.
• [98]Pittas AG,Lau J,Hu FB,Dawson-Hughes B.The role of vitamin D and calcium in type 2 diabetes.A systematic review and meta-analysis[J].J Clin Endocrinol Metab,2007,92:2017-2029.
• [99]Sisley SR,Arble DM,Chambers AP,et al.Hypothalamic vitamin D improves glucose homeostasis and reduces weight[J].Diabetes,2016,65:2732-2741.
• [100]Chen S,Glenn DJ,Ni W,et al.Expression of the vitamin D receptor is increased in the hypertrophic heart[J].Hypertension,2008,52:1106-1112.
• [101]Zanetti M,Harris SS,Dawson-Hughes B.Ability of vitamin D to reduce inflammation in adults without acute illness[J].Nutr Rev,2014,72:95-98.
• [102]Hansen D,Rasmussen K,Rasmussen LM,et al.The influence of vitamin D analogs on calcification modulators,Nterminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients:a randomized crossover study[J].BMC Nephrol,2014,15:130.
• [103]Norman PE,Powell JT.Vitamin D and cardiova-scular disease[J].Circ Res,2014,114:379-393.
• [104]Adami S,Viapiana O,Gatti D,et al.Relationship between serum parathyroid hormone,vitamin D sufficiency,age,and calcium intake[J].Bone,2008,42:267-270.
• [105]Cho HJ,Kang HC,Choi SA,et al.The possible role of Ca2+on the activation of microsomal triglyceride transfer protein in rat hepatocytes[J].Bio Pharm Bull,2005,28:1418-1423.
• [106]Giovinazzo S,Alibrandi A,Campenni A,et al.Correlation of cardio-metabolic parameters with vitamin D status in healthy premenopausal women[J].J Endocrinol Invest,2017,40:1337-1343.
• [107]Hao Y,Ma X,Luo Y,et al.Additional role of serum 25-hydroxyvitamin D3levels in atherosclerosis in Chinese middle-aged and elderly men[J].Clin Exp Pharmacol Physiol,2014,41:174-179.
• [108]Milazzo V,Metrio MD,Cosentino N,et al.Vitamin D and acute myocardial infarction[J].World J Cardiol,2017,9:14-20.
• [109]Gotsman I,Shauer A,Zwas DR,et al.Vitamin D deficiency is a predictor of reduced survival in patients with heart failure,vitamin D supplementation improves outcome[J].Eur J Heart Fail,2012,14:357-366.
• [110]Afshari L,Amani R,Soltani F,et al.The relation between serum Vitamin D levels and body antioxidant status in ischemic stroke patients:a case-control study[J].Adv Biomed Res,2015,4:213.
• [111]Anderson JL,May HT,Horne BD,et al.Relation of vitamin D deficiency to cardiovascular risk factors,disease status,and incident events in a general healthcare population[J].Am J Cardiol,2010,106:963-968.
• [112]Pérez-Hernndez N,Aptilon-Duque G,Nostroza-Hernndez MC,et al.Vitamin D and its effects on cardiovascular diseases:a comprehensive review[J].Korean J Intern Med,2016,31:1018-1029.
• [113]Schleithoff SS,Zittermann A,Tenderich G,et al.Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure:a double-blind,randomized,placebo-controlled trial[J].Am J Clin Nutr,2006,83:754-759.
• [114]Endo I,Inoue D,Mitsui T,et al.Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expres-sion of myoregulatory transcription factors[J].Endocrinology,2003,144:5138-5144.
• [115]Srikuea R,Zhang X,Park-Sarge OK,et al.VDR and CYP27B1 are expressed in C2C12 cells and regenerating skeletal muscle:potential role in suppression of myoblast proliferation[J].Am J Physiol Cell Physiol,2012,303:C396-C405.
• [116]Ryan ZC,Craig TA,Folmes CD,et al.1Alpha,25-Dihydroxyvitamin D3regulates mitochondrial oxygen consumption and dynamics in human skeletal muscle cells[J].J Biol Chem,2016,291:1514-1528.
• [117]曾琴,谢忠建.维生素D与骨骼肌[J].中华骨质疏松和骨矿盐疾病杂志,2016,9:103-109.
• [118]Wang Y,De Luca HF.Is the vitamin D receptor found in muscle?[J].Endocrinology,2011,152:354-363.
• [119]Priemel M,von Domarus C,Klatte TO,et al.Bone mineralization defects and vitamin D deficiency:histomorphometric analysis of iliac crest bone biopsies and circulating25-hydroxyvitamin D in 675 patients[J].J Bone Miner Res,2010,25:305-312.
• [120]Rosen CJ,A