{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:07:56Z","timestamp":1773763676328,"version":"3.50.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Calcif Tissue Int"],"published-print":{"date-parts":[[2009,5]]},"DOI":"10.1007\/s00223-009-9244-8","type":"journal-article","created":{"date-parts":[[2009,4,11]],"date-time":"2009-04-11T16:12:42Z","timestamp":1239466362000},"page":"413-422","source":"Crossref","is-referenced-by-count":59,"title":["Vitamin B12 Deficiency Stimulates Osteoclastogenesis via Increased Homocysteine and Methylmalonic Acid"],"prefix":"10.1007","volume":"84","author":[{"given":"Bart L. T.","family":"Vaes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolien","family":"Lute","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk J.","family":"Blom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Bravenboer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teun J.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Everts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalie A.","family":"Dhonukshe-Rutten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisette C. P. G. M.","family":"de Groot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilma T.","family":"Steegenga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2009,4,12]]},"reference":[{"key":"9244_CR1","doi-asserted-by":"crossref","first-page":"2507S","DOI":"10.1093\/jn\/137.11.2507S","volume":"137","author":"KD Cashman","year":"2007","unstructured":"Cashman KD (2007) Diet, nutrition, and bone health. J Nutr 137:2507S\u20132512S","journal-title":"J Nutr"},{"key":"9244_CR2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1080\/10408390500466174","volume":"46","author":"C Palacios","year":"2006","unstructured":"Palacios C (2006) The role of nutrients in bone health, from A to Z. Crit Rev Food Sci Nutr 46:621\u2013628","journal-title":"Crit Rev Food Sci Nutr"},{"key":"9244_CR3","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1079\/PNS2006519","volume":"65","author":"A Prentice","year":"2006","unstructured":"Prentice A, Schoenmakers I, Laskey MA, de Bono S, Ginty F, Goldberg GR (2006) Nutrition and bone growth and development. Proc Nutr Soc 65:348\u2013360","journal-title":"Proc Nutr Soc"},{"key":"9244_CR4","doi-asserted-by":"crossref","first-page":"1232S","DOI":"10.1093\/ajcn\/81.5.1232","volume":"81","author":"JW Nieves","year":"2005","unstructured":"Nieves JW (2005) Osteoporosis: the role of micronutrients. Am J Clin Nutr 81:1232S\u20131239S","journal-title":"Am J Clin Nutr"},{"key":"9244_CR5","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1093\/jn\/133.3.801","volume":"133","author":"RA Dhonukshe-Rutten","year":"2003","unstructured":"Dhonukshe-Rutten RA, Lips M, de Jong N, Chin APMJ, Hiddink GJ, van Dusseldorp M, De Groot LC, van Staveren WA (2003) Vitamin B12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men. J Nutr 133:801\u2013807","journal-title":"J Nutr"},{"key":"9244_CR6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00394-004-0531-x","volume":"44","author":"RA Dhonukshe-Rutten","year":"2005","unstructured":"Dhonukshe-Rutten RA, van Dusseldorp M, Schneede J, de Groot LC, van Staveren WA (2005) Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents. Eur J Nutr 44:341\u2013347","journal-title":"Eur J Nutr"},{"key":"9244_CR7","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/jbmr.5650070514","volume":"7","author":"JB Goerss","year":"1992","unstructured":"Goerss JB, Kim CH, Atkinson EJ, Eastell R, O\u2019Fallon WM, Melton LJ III (1992) Risk of fractures in patients with pernicious anemia. J Bone Miner Res 7:573\u2013579","journal-title":"J Bone Miner Res"},{"key":"9244_CR8","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1210\/jc.2003-030074","volume":"89","author":"KL Stone","year":"2004","unstructured":"Stone KL, Bauer DC, Sellmeyer D, Cummings SR (2004) Low serum vitamin B12 levels are associated with increased hip bone loss in older women: a prospective study. J Clin Endocrinol Metab 89:1217\u20131221","journal-title":"J Clin Endocrinol Metab"},{"key":"9244_CR9","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1359\/jbmr.2005.20.1.152","volume":"20","author":"KL Tucker","year":"2005","unstructured":"Tucker KL, Hannan MT, Qiao N, Jacques PF, Selhub J, Cupples LA, Kiel DP (2005) Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J Bone Miner Res 20:152\u2013158","journal-title":"J Bone Miner Res"},{"key":"9244_CR10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/bse0340139","volume":"34","author":"EN Marsh","year":"1999","unstructured":"Marsh EN (1999) Coenzyme B12 (cobalamin)-dependent enzymes. Essays Biochem 34:139\u2013154","journal-title":"Essays Biochem"},{"key":"9244_CR11","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1001\/jama.1993.03510220049033","volume":"270","author":"J Selhub","year":"1993","unstructured":"Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 270:2693\u20132698","journal-title":"JAMA"},{"key":"9244_CR12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.nutr.19.1.357","volume":"19","author":"HW Baik","year":"1999","unstructured":"Baik HW, Russell RM (1999) Vitamin B12 deficiency in the elderly. Annu Rev Nutr 19:357\u2013377","journal-title":"Annu Rev Nutr"},{"key":"9244_CR13","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1359\/JBMR.050202","volume":"20","author":"RA Dhonukshe-Rutten","year":"2005","unstructured":"Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, Lips P, Smit JH, van Staveren WA (2005) Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 20:921\u2013929","journal-title":"J Bone Miner Res"},{"key":"9244_CR14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bone.2005.04.017","volume":"37","author":"MS Morris","year":"2005","unstructured":"Morris MS, Jacques PF, Selhub J (2005) Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 37:234\u2013242","journal-title":"Bone"},{"key":"9244_CR15","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.bone.2006.10.008","volume":"40","author":"M Baines","year":"2007","unstructured":"Baines M, Kredan MB, Usher J, Davison A, Higgins G, Taylor W, West C, Fraser WD, Ranganath LR (2007) The association of homocysteine and its determinants MTHFR genotype, folate, vitamin B12 and vitamin B6 with bone mineral density in postmenopausal British women. Bone 40:730\u2013736","journal-title":"Bone"},{"key":"9244_CR16","first-page":"314","volume":"42","author":"A Cagnacci","year":"2008","unstructured":"Cagnacci A, Bagni B, Zini A, Cannoletta M, Generali M, Volpe A (2008) Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation. Bone 42:314\u2013320","journal-title":"A five-year longitudinal evaluation. Bone"},{"key":"9244_CR17","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.bone.2003.07.001","volume":"33","author":"A Cagnacci","year":"2003","unstructured":"Cagnacci A, Baldassari F, Rivolta G, Arangino S, Volpe A (2003) Relation of homocysteine, folate, and vitamin B12 to bone mineral density of postmenopausal women. Bone 33:956\u2013959","journal-title":"Bone"},{"key":"9244_CR18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1359\/jbmr.061003","volume":"22","author":"P Gerdhem","year":"2007","unstructured":"Gerdhem P, Ivaska KK, Isaksson A, Pettersson K, Vaananen HK, Obrant KJ, Akesson K (2007) Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women. J Bone Miner Res 22:127\u2013134","journal-title":"J Bone Miner Res"},{"key":"9244_CR19","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1359\/jbmr.070210","volume":"22","author":"CG Gjesdal","year":"2007","unstructured":"Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Meyer HE, Tell GS (2007) Plasma homocysteine, folate, and vitamin B12 and the risk of hip fracture: the Hordaland Homocysteine Study. J Bone Miner Res 22:747\u2013756","journal-title":"J Bone Miner Res"},{"key":"9244_CR20","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1056\/NEJMoa032546","volume":"350","author":"JB Meurs van","year":"2004","unstructured":"van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, de Groot LC, Hofman A, Witteman JC, van Leeuwen JP, Breteler MM, Lips P, Pols HA, Uitterlinden AG (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033\u20132041","journal-title":"N Engl J Med"},{"key":"9244_CR21","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1056\/NEJMoa032739","volume":"350","author":"RR McLean","year":"2004","unstructured":"McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, Hannan MT, Cupples LA, Kiel DP (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042\u20132049","journal-title":"N Engl J Med"},{"key":"9244_CR22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1056\/NEJM198807143190202","volume":"319","author":"R Carmel","year":"1988","unstructured":"Carmel R, Lau KH, Baylink DJ, Saxena S, Singer FR (1988) Cobalamin and osteoblast-specific proteins. N Engl J Med 319:70\u201375","journal-title":"N Engl J Med"},{"key":"9244_CR23","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.bone.2007.06.005","volume":"41","author":"M Herrmann","year":"2007","unstructured":"Herrmann M, Schmidt J, Umanskaya N, Colaianni G, Al Marrawi F, Widmann T, Zallone A, Wildemann B, Herrmann W (2007) Stimulation of osteoclast activity by low B-vitamin concentrations. Bone 41:584\u2013591","journal-title":"Bone"},{"key":"9244_CR24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cca.2007.06.016","volume":"384","author":"M Herrmann","year":"2007","unstructured":"Herrmann M, Umanskaya N, Wildemann B, Colaianni G, Schmidt J, Widmann T, Zallone A, Herrmann W (2007) Accumulation of homocysteine by decreasing concentrations of folate, vitamin B12 and B6 does not influence the activity of human osteoblasts in vitro. Clin Chim Acta 384:129\u2013134","journal-title":"Clin Chim Acta"},{"key":"9244_CR25","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/S0026-0495(96)90171-7","volume":"45","author":"GS Kim","year":"1996","unstructured":"Kim GS, Kim CH, Park JY, Lee KU, Park CS (1996) Effects of vitamin B12 on cell proliferation and cellular alkaline phosphatase activity in human bone marrow stromal osteoprogenitor cells and UMR106 osteoblastic cells. Metabolism 45:1443\u20131446","journal-title":"Metabolism"},{"key":"9244_CR26","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1359\/jbmr.060406","volume":"21","author":"JM Koh","year":"2006","unstructured":"Koh JM, Lee YS, Kim YS, Kim DJ, Kim HH, Park JY, Lee KU, Kim GS (2006) Homocysteine enhances bone resorption by stimulation of osteoclast formation and activity through increased intracellular ROS generation. J Bone Miner Res 21:1003\u20131011","journal-title":"J Bone Miner Res"},{"key":"9244_CR27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bbadis.2005.03.004","volume":"1740","author":"W Sakamoto","year":"2005","unstructured":"Sakamoto W, Isomura H, Fujie K, Deyama Y, Kato A, Nishihira J, Izumi H (2005) Homocysteine attenuates the expression of osteocalcin but enhances osteopontin in MC3T3-E1 preosteoblastic cells. Biochim Biophys Acta 1740:12\u201316","journal-title":"Biochim Biophys Acta"},{"issue":"Pt 2","key":"9244_CR28","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1177\/000456329503200218","volume":"32","author":"MT Poele-Pothoff te","year":"1995","unstructured":"te Poele-Pothoff MT, van den Berg M, Franken DG, Boers GH, Jakobs C, de Kroon IF, Eskes TK, Trijbels JM, Blom HJ (1995) Three different methods for the determination of total homocysteine in plasma. Ann Clin Biochem 32(Pt 2):218\u2013220","journal-title":"Ann Clin Biochem"},{"key":"9244_CR29","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1002\/jcb.20326","volume":"94","author":"TJ Vries de","year":"2005","unstructured":"de Vries TJ, Schoenmaker T, Beertsen W, van der Neut R, Everts V (2005) Effect of CD44 deficiency on in vitro and in vivo osteoclast formation. J Cell Biochem 94:954\u2013966","journal-title":"J Cell Biochem"},{"key":"9244_CR30","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/(SICI)1097-4644(199702)64:2<295::AID-JCB12>3.0.CO;2-I","volume":"64","author":"N Jaiswal","year":"1997","unstructured":"Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP (1997) Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64:295\u2013312","journal-title":"J Cell Biochem"},{"key":"9244_CR31","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","volume":"284","author":"MF Pittenger","year":"1999","unstructured":"Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143\u2013147","journal-title":"Science"},{"key":"9244_CR32","first-page":"13","volume-title":"Primer on the metabolic bone diseases and disorders of mineral metabolism","author":"JB Lian","year":"2003","unstructured":"Lian JB, Stein GS, Aubin JE (2003) Bone formation: maturation and functional activities of osteoblast lineage cells. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism. American Society for Bone and Mineral Research, Washington DC, pp 13\u201328"},{"key":"9244_CR33","first-page":"1118","volume":"43","author":"M Herrmann","year":"2005","unstructured":"Herrmann M, Kraenzlin M, Pape G, Sand-Hill M, Herrmann W (2005) Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women. Clin Chem Lab Med 43:1118\u20131123","journal-title":"Clin Chem Lab Med"},{"key":"9244_CR34","first-page":"1621","volume":"45","author":"M Herrmann","year":"2007","unstructured":"Herrmann M, Peter Schmidt J, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T, Colaianni G, Wildemann B, Herrmann W (2007) The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med 45:1621\u20131632","journal-title":"Clin Chem Lab Med"},{"key":"9244_CR35","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1080\/00365510701342088","volume":"67","author":"S Ozdem","year":"2007","unstructured":"Ozdem S, Samanci S, Tasatargil A, Yildiz A, Sadan G, Donmez L, Herrmann M (2007) Experimental hyperhomocysteinemia disturbs bone metabolism in rats. Scand J Clin Lab Invest 67:748\u2013756","journal-title":"Scand J Clin Lab Invest"},{"key":"9244_CR36","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1001\/archinte.165.10.1167","volume":"165","author":"SJ Eussen","year":"2005","unstructured":"Eussen SJ, de Groot LC, Clarke R, Schneede J, Ueland PM, Hoefnagels WH, van Staveren WA (2005) Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med 165:1167\u20131172","journal-title":"Arch Intern Med"},{"key":"9244_CR37","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/ajcn\/84.2.361","volume":"84","author":"SJ Eussen","year":"2006","unstructured":"Eussen SJ, de Groot LC, Joosten LW, Bloo RJ, Clarke R, Ueland PM, Schneede J, Blom HJ, Hoefnagels WH, van Staveren WA (2006) Effect of oral vitamin B12 with or without folic acid on cognitive function in older people with mild vitamin B12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr 84:361\u2013370","journal-title":"Am J Clin Nutr"},{"key":"9244_CR38","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1093\/ajcn\/77.5.1318","volume":"77","author":"FV Oort van","year":"2003","unstructured":"van Oort FV, Melse-Boonstra A, Brouwer IA, Clarke R, West CE, Katan MB, Verhoef P (2003) Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose\u2013response study. Am J Clin Nutr 77:1318\u20131323","journal-title":"Am J Clin Nutr"},{"key":"9244_CR39","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1046\/j.1532-5415.2002.50506.x","volume":"50","author":"S Rajan","year":"2002","unstructured":"Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP (2002) Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc 50:1789\u20131795","journal-title":"J Am Geriatr Soc"},{"key":"9244_CR40","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2165\/00044011-199714050-00013","volume":"14","author":"H Mulder","year":"1997","unstructured":"Mulder H, Snelder HAA (1997) Vitamin B12 replacement and its effects on bone mass and bone markers in patients with osteoporosis associated with pernicious anaemia. Clin Drug Invest 14:434\u2013437","journal-title":"Clin Drug Invest"},{"key":"9244_CR41","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1001\/jama.293.9.1082","volume":"293","author":"Y Sato","year":"2005","unstructured":"Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K (2005) Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 293:1082\u20131088","journal-title":"JAMA"},{"key":"9244_CR42","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1093\/ajcn\/85.2.460","volume":"85","author":"TJ Green","year":"2007","unstructured":"Green TJ, McMahon JA, Skeaff CM, Williams SM, Whiting SJ (2007) Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial. Am J Clin Nutr 85:460\u2013464","journal-title":"Am J Clin Nutr"},{"key":"9244_CR43","first-page":"131","volume":"52","author":"M Herrmann","year":"2006","unstructured":"Herrmann M, Stanger O, Paulweber B, Hufnagl C, Herrmann W (2006) Folate supplementation does not affect biochemical markers of bone turnover. Clin Lab 52:131\u2013136","journal-title":"Clin Lab"}],"container-title":["Calcified Tissue International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00223-009-9244-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T12:24:55Z","timestamp":1550579095000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00223-009-9244-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,12]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2009,5]]}},"alternative-id":["9244"],"URL":"https:\/\/doi.org\/10.1007\/s00223-009-9244-8","relation":{},"ISSN":["0171-967X","1432-0827"],"issn-type":[{"value":"0171-967X","type":"print"},{"value":"1432-0827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,12]]}}}