{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:51:51Z","timestamp":1788277911581,"version":"build-2803163510"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204063, 11971117, 11571082"],"award-info":[{"award-number":["82204063, 11971117, 11571082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>In the progress of bone metabolism, homocysteine (Hcy) and B vitamins play substantial roles. However, the causal associations of homocysteine, B-vitamin concentrations with bone mineral density (BMD), and fractures remain unclear. Therefore, we employed a two-sample Mendelian randomization (MR) design to infer the causal effects of Hcy and B vitamins on BMD and fractures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected instrumental variables from large genome-wide association studies (GWASs). Specifically, the exposures mainly included Hcy (sample size: 44,147), vitamin B12 (sample size: 45,576), folate (sample size: 37,465), and vitamin B6 (sample size: 1,864). The outcome variables included total body BMD (sample size: 66,628), heel BMD (sample size: 142,487), femoral neck BMD (sample size: 32,735), lumbar spine BMD (sample size: 28,498), and forearm BMD (sample size: 8143). Additionally, the total body BMD in several age strata was also included. Furthermore, the fractures of the forearm, femoral neck, lumbar spine, heel corresponding with the BMD regions, and femoral neck and lumbar spine BMD in men and women, separately, were added as additional outcomes. Two-sample MR approaches were utilized in this study. Inverse variance weighting (IVW) was adopted as the main analysis. MR-PRESSO, MR-Egger, the weighted median estimate, and multivariable MR were performed as sensitivity methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the main analysis, Hcy concentrations have an inverse association with heel BMD (Beta = 0.046, 95% confidence interval (CI) -0.073 to -0.019, <jats:italic>P<\/jats:italic> = 9.59E-04) per SD unit. In addition, for one SD increase of vitamin B12, the total body BMD decreased 0.083 unit (95%CI -0.126 to -0.040, <jats:italic>P<\/jats:italic> = 1.65E-04). The trend was more obvious in age over 45 years (Beta = -0.135, 95%CI -0.203\u20130.067, <jats:italic>P<\/jats:italic> = 9.86E-05 for age 45-60; Beta = -0.074, 95%CI -0.141 to -0.007, <jats:italic>P<\/jats:italic> = 0.031 for age over 60 years). No association of B vitamins and Hcy levels with the risk of fractures and femoral neck and lumbar spine BMD in men and women was found in this study. Other sensitivity MR methods elucidated consistent results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicated that there exist the inversely causal effects of Hcy and vitamin B12 on BMD in certain body sites and age strata. These give novel clues for intervening bone-related diseases in public health and nutrition.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1037546","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:05:57Z","timestamp":1669619157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Inferring causal effects of homocysteine and B-vitamin concentrations on bone mineral density and fractures: Mendelian randomization analyses"],"prefix":"10.3389","volume":"13","author":[{"given":"Liwan","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuquan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Qing","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.6.785","article-title":"Osteoporosis prevention, diagnosis, and therapy","volume":"285","year":"2001","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1660790","article-title":"Osteoporosis: Current concepts","volume":"6","author":"Akkawi","year":"2018","journal-title":"Joints"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1671","article-title":"Change in hip bone mineral density and risk of subsequent fractures in older men","volume":"27","author":"Cawthon","year":"2012","journal-title":"J Bone Miner Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1056\/NEJMx160008","article-title":"Postmenopausal osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/pl00004156","article-title":"Epidemiology of osteoporosis","author":"Cooper","year":"1999","journal-title":"Osteop Int"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s11657-013-0136-1","article-title":"Osteoporosis in the European union: medical management, epidemiology and economic burden. A report prepared in collaboration with the international osteoporosis foundation (IOF) and the European federation of pharmaceutical industry associations (EFPIA)","volume":"8","author":"Hernlund","year":"2013","journal-title":"Arch Osteop"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.3.0464","article-title":"Genetics of osteoporosis","volume":"23","author":"Peacock","year":"2002","journal-title":"Endocr Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ajhg.2017.12.005","article-title":"Life-course genome-wide association study meta-analysis of total body BMD and assessment of age-specific effects","volume":"102","author":"Medina-Gomez","year":"2018","journal-title":"Am J Hum Genet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.14740\/jocmr2970w","article-title":"Gender disparities in osteoporosis","volume":"9","author":"Alswat","year":"2017","journal-title":"J Clin Med Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa579","article-title":"Parathyroid hormone and bone mineral density: A mendelian randomization study","volume":"105","author":"Qu","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.5455\/medarh.2017.71.25-28","article-title":"Risk factors for osteoporosis in postmenopausal women","volume":"71","author":"Bijelic","year":"2017","journal-title":"Med Arch"},{"key":"B12","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.drugalcdep.2019.01.025","article-title":"The effect of alcohol on osteoporosis: A systematic review and meta-analysis","volume":"197","author":"Cheraghi","year":"2019","journal-title":"Drug Alcohol Depend"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510220049033","article-title":"Vitamin status and intake as primary determinants of homocysteinemia in an elderly population","volume":"270","author":"Selhub","year":"1993","journal-title":"JAMA"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/73.3.613","article-title":"Determinants of plasma total homocysteine concentration in the framingham offspring cohort","volume":"73","author":"Jacques","year":"2001","journal-title":"Am J Clin Nutr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032739","article-title":"Homocysteine as a predictive factor for hip fracture in older persons","volume":"350","author":"McLean","year":"2004","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032546","article-title":"Homocysteine levels and the risk of osteoporotic fracture","volume":"350","author":"van Meurs","year":"2004","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1515\/cclm.2005.195","article-title":"Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women","volume":"43","author":"Herrmann","year":"2005","journal-title":"Clin Chem Lab Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1001\/archinte.166.1.88","article-title":"Plasma total homocysteine level and bone mineral density: The hordaland homocysteine study","volume":"166","author":"Gjesdal","year":"2006","journal-title":"Arch Intern Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1016\/0140-6736(91)92782-w","article-title":"Homocyst(e)inaemia and bone density in elderly women","volume":"338","author":"Browner","year":"1991","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.07.001","article-title":"Relation of homocysteine, folate, and vitamin B12 to bone mineral density of postmenopausal women","volume":"33","author":"Cagnacci","year":"2003","journal-title":"Bone"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.04.018","article-title":"Association of plasma folate, plasma total homocysteine, but not methylenetetrahydrofolate reductase C667T polymorphism, with bone mineral density in postmenopausal Iranian women: a cross-sectional study","volume":"35","author":"Golbahar","year":"2004","journal-title":"Bone"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/00365510500348153","article-title":"Plasma homocysteine and markers of bone metabolism in psychogeriatric patients","volume":"65","author":"Nilsson","year":"2005","journal-title":"Scand J Clin Lab Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.090043","article-title":"Effect of daily vitamin b-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial","volume":"100","author":"van Wijngaarden","year":"2014","journal-title":"Am J Clin Nutr"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-9968-6","article-title":"Effect of vitamin B12 and folic acid supplementation on bone mineral density and quantitative ultrasound parameters in older people with an elevated plasma homocysteine level: B-PROOF, a randomized controlled trial","volume":"96","author":"Enneman","year":"2015","journal-title":"Calcif Tissue Int"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe048030","article-title":"Homocysteine and osteoporotic fractures\u2013culprit or bystander","volume":"350","author":"Raisz","year":"2004","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-017-0128-6","article-title":"Recent developments in mendelian randomization studies","volume":"4","author":"Zheng","year":"2017","journal-title":"Curr Epidemiol Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006944","article-title":"Genetic epidemiology and mendelian randomization for informing disease therapeutics: Conceptual and methodological challenges","volume":"13","author":"Paternoster","year":"2017","journal-title":"PloS Genet"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s205379","article-title":"Plausible relationship between homocysteine and obesity risk via MTHFR gene: A meta-analysis of 38,317 individuals implementing mendelian randomization","volume":"12","author":"Fu","year":"2019","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-018-0469-1","article-title":"The effects of homocysteine on the skeleton","volume":"16","author":"Saito","year":"2018","journal-title":"Curr Osteop Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.11005\/jbm.2016.23.3.129","article-title":"Association between homocysteine and bone mineral density according to age and sex in healthy adults","volume":"23","author":"Kim","year":"2016","journal-title":"J Bone Metab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s11657-018-0525-6","article-title":"Association of high-density lipoprotein, triglycerides, and homocysteine with bone mineral density in young Indian tribal women","volume":"13","author":"Saoji","year":"2018","journal-title":"Arch Osteop"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqab093","article-title":"Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin b-12, vitamin b-6, and folate with bone mineral density","volume":"114","author":"Liu","year":"2021","journal-title":"Am J Clin Nutr"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw127","article-title":"Commentary: Two-sample mendelian randomization: opportunities and challenges","volume":"45","author":"Lawlor","year":"2016","journal-title":"Int J Epidemiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","article-title":"Reading mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-022-00874-5","article-title":"Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in mendelian randomization","volume":"37","author":"Yang","year":"2022","journal-title":"Eur J Epidemiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003530","article-title":"Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets","volume":"9","author":"Grarup","year":"2013","journal-title":"PloS Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.044545","article-title":"Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease","volume":"98","author":"van Meurs","year":"2013","journal-title":"Am J Clin Nutr"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.02.011","article-title":"Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations","volume":"84","author":"Tanaka","year":"2009","journal-title":"Am J Hum Genet"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: An expanded tool for searching human genotype-phenotype associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinformatics"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-11-837","article-title":"Which fractures are associated with low appendicular bone mass in elderly women? the study of osteoporotic fractures research group","volume":"115","author":"Seeley","year":"1991","journal-title":"Ann Intern Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.11.1947","article-title":"BMD at multiple sites and risk of fracture of multiple types: long-term results from the study of osteoporotic fractures","volume":"18","author":"Stone","year":"2003","journal-title":"J Bone Miner Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nature14878","article-title":"Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture","volume":"526","author":"Zheng","year":"2015","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3949","article-title":"Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis","volume":"49","author":"Kemp","year":"2017","journal-title":"Nat Genet"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.7326\/aitc201708010","article-title":"Osteoporosis","volume":"167","author":"Ensrud","year":"2017","journal-title":"Ann Intern Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.2249","article-title":"Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture","volume":"44","author":"Estrada","year":"2012","journal-title":"Nat Genet"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0147-3","article-title":"Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals","volume":"50","author":"Lee","year":"2018","journal-title":"Nat Genet"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0307-5","article-title":"Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use","volume":"51","author":"Liu","year":"2019","journal-title":"Nat Genet"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7221","article-title":"A framework for the investigation of pleiotropy in two-sample summary data mendelian randomization","volume":"36","author":"Bowden","year":"2017","journal-title":"Stat Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu283","article-title":"Multivariable mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects","volume":"181","author":"Burgess","year":"2015","journal-title":"Am J Epidemiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt179","article-title":"Calculating statistical power in mendelian randomization studies","volume":"42","author":"Brion","year":"2013","journal-title":"Int J Epidemiol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw613","article-title":"LD hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis","volume":"33","author":"Zheng","year":"2017","journal-title":"Bioinformatics"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.7554\/elife.34408","article-title":"The MR-base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx034","article-title":"MendelianRandomization: an r package for performing mendelian randomization analyses using summarized data","volume":"46","author":"Yavorska","year":"2017","journal-title":"Int J Epidemiol"},{"key":"B58","article-title":"Relationship of homocysteine levels with lumbar spine and femur neck BMD in postmenopausal women","volume":"40","author":"Bahtiri","year":"2015","journal-title":"Acta Reum Port"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10390","article-title":"Association of heel bone mineral density with incident disability and mortality in community-dwelling older adults","volume":"4","author":"Ross","year":"2020","journal-title":"JBMR Plus"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17124260","article-title":"Hyperhomocysteinemia is associated with inflammation, bone resorption, vitamin B12 and folate deficiency and MTHFR C677T polymorphism in postmenopausal women with decreased bone mineral density","volume":"17","author":"De Martinis","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.04.017","article-title":"Relation between homocysteine and b-vitamin status indicators and bone mineral density in older americans","volume":"37","author":"Morris","year":"2005","journal-title":"Bone"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.041018","article-title":"Low plasma vitamin B12 is associated with lower BMD: the framingham osteoporosis study","volume":"20","author":"Tucker","year":"2005","journal-title":"J Bone Miner Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.10.008","article-title":"The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women","volume":"40","author":"Baines","year":"2007","journal-title":"Bone"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2021.02.045","article-title":"Causal effects of homocysteine levels on the changes of bone mineral density and risk for bone fracture: A two-sample mendelian randomization study","volume":"40","author":"Wang","year":"2021","journal-title":"Clin Nutr"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.09.019","article-title":"Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population","volume":"679","author":"Fu","year":"2018","journal-title":"Gene"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/jch.13737","article-title":"Evidence on the causal link between homocysteine and hypertension from a meta-analysis of 40 173 individuals implementing mendelian randomization","volume":"21","author":"Fu","year":"2019","journal-title":"J Clin Hypertens"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.654804","article-title":"A novel approach integrating hierarchical clustering and weighted combination for association study of multiple phenotypes and a genetic variant","volume":"12","author":"Fu","year":"2021","journal-title":"Front Genet"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2022.03.030","article-title":"Distinct causal effects of body fat distribution on cardiometabolic traits among children: Findings from the BCAMS study","volume":"32","author":"Fu","year":"2022","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1048122","article-title":"Causal effects of B vitamins, homocysteine on fat and musculoskeletal diseases: A Mendelian randomization study","volume":"9","author":"Fu","year":"2022","journal-title":"Front Nutr"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13895","article-title":"Association between homocysteine and nonalcoholic fatty liver disease: Mendelian randomisation study","author":"Fu","year":"2022","journal-title":"Eur J Clin Invest"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.791920","article-title":"A novel hierarchical clustering approach for joint analysis of multiple phenotypes uncovers obesity variants based on ARIC","volume":"13","author":"Fu","year":"2022","journal-title":"Front Genet"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(95)00119-0","article-title":"Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria","volume":"1315","author":"Lubec","year":"1996","journal-title":"Biochim Biophys Acta"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21415","article-title":"Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid","volume":"29","author":"Tyagi","year":"2011","journal-title":"J Orthop Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.03.004","article-title":"Homocysteine enhances apoptosis in human bone marrow stromal cells","volume":"39","author":"Kim","year":"2006","journal-title":"Bone"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060406","article-title":"Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation","volume":"21","author":"Koh","year":"2006","journal-title":"J Bone Miner Res"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-016-0211-x","article-title":"Bazedoxifene ameliorates homocysteine-induced apoptosis and accumulation of advanced glycation end products by reducing oxidative stress in MC3T3-E1 cells","volume":"100","author":"Kanazawa","year":"2017","journal-title":"Calcif Tissue Int"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-018-4461-5","article-title":"Bone mineral density averaged over a region of interest on femur is affected by age-related change of bone geometry","volume":"29","author":"Luo","year":"2018","journal-title":"Osteop Int"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2017.06.013","article-title":"Thoracic quantitative computed tomography (QCT) can sensitively monitor bone mineral metabolism: Comparison of thoracic QCT vs lumbar QCT and dual-energy X-ray absorptiometry in detection of age-relative change in bone mineral density","volume":"24","author":"Mao","year":"2017","journal-title":"Acad Radiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1037546\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:06:01Z","timestamp":1669619161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1037546\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,28]]},"references-count":78,"alternative-id":["10.3389\/fendo.2022.1037546"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1037546","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,28]]},"article-number":"1037546"}}