{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:25:13Z","timestamp":1792009513605,"version":"4.4.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Chronic kidney disease and osteoporosis are major public health problems associated with an aging population. Vitamin K insufficiency is prevalent among patients with end-stage renal disease (ESRD). Preliminary data indicate that poor vitamin K status may compromise bone health and that increased inflammation may be in the causal pathway. We performed an ancillary analysis of data collected in the frame of prospective observational cohort studies exploring various aspects of bone health in de novo renal transplant recipients to investigate the association between vitamin K status, inflammation, bone mineral density, and incident clinical fractures. Parameters of mineral metabolism (including biointact PTH and FGF23, sclerostin, calcidiol, calcitriol) and inflammation (CRP and IL-6), osteoprotegerin, bone turnover markers (P1NP, BsAP, and TRAP5B), and dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP) were assessed on blood samples collected immediately prior to kidney transplantation in 468 patients. Areal bone mineral density (aBMD) was measured at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry within 14 days posttransplant. Poor vitamin K status, defined by dp-ucMGP &amp;gt;500\u2009nmol\/L, was highly prevalent (90%). High dp-ucMGP levels independently associated with elevated inflammatory markers and low aBMD. No associations were observed between vitamin K status and bone turnover markers. During a median follow-up of 5.1 years, 33 patients sustained a fragility fracture. In Cox-proportional hazards analysis, a dp-ucMGP above median associated with incident fractures, independent of classical determinants, including age, gender, history of fracture, and aBMD (HR 2.21; 95% CI, 1.00 to 4.91; p\u2009&amp;lt;\u20090.05). In conclusion, poor vitamin K status associates with inflammation and low aBMD in patients with ESRD and confers an increased risk of incident fractures in de novo renal transplant recipients. \u00a9 2018 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3608","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T16:23:16Z","timestamp":1542212596000},"page":"262-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Poor Vitamin K Status Is Associated With Low Bone Mineral Density and Increased Fracture Risk in End-Stage Renal Disease"],"prefix":"10.1093","volume":"34","author":[{"given":"Pieter","family":"Evenepoel","sequence":"first","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Claes","sequence":"additional","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Meijers","sequence":"additional","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u00ebl","family":"Laurent","sequence":"additional","affiliation":[{"name":"Centre for Metabolic Bone DiseasesKU LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Bammens","sequence":"additional","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Naesens","sequence":"additional","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Sprangers","sequence":"additional","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Pottel","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary CareKU Leuven Campus Kulak KortrijkKortrijkBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Cavalier","sequence":"additional","affiliation":[{"name":"Clinical ChemistryUniversit\u00e9 de Li\u00e8geLi\u00e8geBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of NephrologyUniversity Hospitals LeuvenLeuvenBelgium"},{"name":"Laboratory of NephrologyDepartment of Microbiology and ImmunologyKatholieke Universiteit (KU) LeuvenLeuvenBelgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"issue":"7","key":"2024021014513164700_jbmr3608-bib-0001","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/sj.ki.5001754","article-title":"Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study","volume":"70","author":"Jadoul","year":"2006","journal-title":"Kidney Int"},{"issue":"23","key":"2024021014513164700_jbmr3608-bib-0002","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.1001\/jama.288.23.3014","article-title":"Risk of hip fracture among dialysis and renal transplant recipients","volume":"288","author":"Ball","year":"2002","journal-title":"JAMA"},{"issue":"2","key":"2024021014513164700_jbmr3608-bib-0003","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/ajcn\/88.2.356","article-title":"Vitamin K, circulating cytokines, and bone mineral density in older men and women","volume":"88","author":"Shea","year":"2008","journal-title":"Am J Clin Nutr"},{"issue":"10","key":"2024021014513164700_jbmr3608-bib-0004","doi-asserted-by":"crossref","first-page":"4904","DOI":"10.1210\/jc.2003-031673","article-title":"Associations between vitamin K biochemical measures and bone mineral density in men and women","volume":"89","author":"Booth","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2024021014513164700_jbmr3608-bib-0005","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.bone.2011.03.767","article-title":"Dietary vitamin K intake is associated with bone quantitative ultrasound measurements but not with bone peripheral biochemical markers in elderly men and women","volume":"48","author":"Bullo","year":"2011","journal-title":"Bone"},{"issue":"5","key":"2024021014513164700_jbmr3608-bib-0006","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.bone.2011.07.035","article-title":"Intake of vitamin K1 and K2 and risk of hip fractures: the Hordaland Health Study","volume":"49","author":"Apalset","year":"2011","journal-title":"Bone"},{"issue":"1","key":"2024021014513164700_jbmr3608-bib-0007","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ki.2009.126","article-title":"Vitamin K deficiency in CKD patients: a modifiable risk factor for vascular calcification","volume":"76","author":"Krueger","year":"2009","journal-title":"Kidney Int"},{"issue":"4","key":"2024021014513164700_jbmr3608-bib-0008","doi-asserted-by":"crossref","first-page":"590","DOI":"10.2215\/CJN.06420909","article-title":"Vitamins K and D status in stages 3-5 chronic kidney disease","volume":"5","author":"Holden","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"issue":"5","key":"2024021014513164700_jbmr3608-bib-0009","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/ki.2012.191","article-title":"Vitamin K intake and status are low in hemodialysis patients","volume":"82","author":"Cranenburg","year":"2012","journal-title":"Kidney Int"},{"issue":"2","key":"2024021014513164700_jbmr3608-bib-0010","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1681\/ASN.2010040339","article-title":"Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD","volume":"22","author":"Schlieper","year":"2011","journal-title":"J Am Soc Nephrol"},{"issue":"10","key":"2024021014513164700_jbmr3608-bib-0011","doi-asserted-by":"crossref","first-page":"e47991","DOI":"10.1371\/journal.pone.0047991","article-title":"Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients","volume":"7","author":"Boxma","year":"2012","journal-title":"PLoS One"},{"issue":"11","key":"2024021014513164700_jbmr3608-bib-0012","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1002\/jbmr.1677","article-title":"Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study","volume":"27","author":"Fusaro","year":"2012","journal-title":"J Bone Miner Res"},{"issue":"4","key":"2024021014513164700_jbmr3608-bib-0013","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/ki.1997.166","article-title":"Bone health of adult hemodialysis patients is related to vitamin K status","volume":"51","author":"Kohlmeier","year":"1997","journal-title":"Kidney Int"},{"issue":"4","key":"2024021014513164700_jbmr3608-bib-0014","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1160\/TH09-11-0786","article-title":"Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species","volume":"104","author":"Cranenburg","year":"2010","journal-title":"Thromb Haemost"},{"key":"2024021014513164700_jbmr3608-bib-0015","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.metabol.2017.01.032","article-title":"Vitamin K and osteoporosis: myth or reality","volume":"70","author":"Palermo","year":"2017","journal-title":"Metabolism"},{"issue":"3","key":"2024021014513164700_jbmr3608-bib-0016","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/aje\/kwm306","article-title":"Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study","volume":"167","author":"Shea","year":"2008","journal-title":"Am J Epidemiol"},{"issue":"12","key":"2024021014513164700_jbmr3608-bib-0017","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1002\/jbmr.2905","article-title":"Inflammatory markers and the risk of hip and vertebral fractures in men: the Osteoporotic Fractures in Men (MrOS)","volume":"31","author":"Cauley","year":"2016","journal-title":"J Bone Miner Res"},{"issue":"11","key":"2024021014513164700_jbmr3608-bib-0018","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/clinchem\/30.11.1731","article-title":"Two direct (nonchromatographic) assays for 25-hydroxyvitamin D","volume":"30","author":"Bouillon","year":"1984","journal-title":"Clin Chem"},{"issue":"5","key":"2024021014513164700_jbmr3608-bib-0019","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/clinchem\/26.5.562","article-title":"A radioimmunoassay for 1,25-dihydroxycholecalciferol","volume":"26","author":"Bouillon","year":"1980","journal-title":"Clin Chem"},{"issue":"2","key":"2024021014513164700_jbmr3608-bib-0020","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/clinchem\/36.2.271","article-title":"Immunoradiometric assay of parathyrin with polyclonal and monoclonal region-specific antibodies","volume":"36","author":"Bouillon","year":"1990","journal-title":"Clin Chem"},{"issue":"13-14","key":"2024021014513164700_jbmr3608-bib-0021","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.clinbiochem.2014.04.007","article-title":"Inter-method variability in bone alkaline phosphatase measurement: clinical impact on the management of dialysis patients","volume":"47","author":"Cavalier","year":"2014","journal-title":"Clin Biochem"},{"issue":"4","key":"2024021014513164700_jbmr3608-bib-0022","doi-asserted-by":"crossref","first-page":"568","DOI":"10.2215\/CJN.07081009","article-title":"The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report","volume":"5","author":"Schurgers","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"issue":"9","key":"2024021014513164700_jbmr3608-bib-0023","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.2215\/CJN.01470209","article-title":"Arteriovenous fistula affects bone mineral density measurements in end-stage renal failure patients","volume":"4","author":"Muxi","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"issue":"3","key":"2024021014513164700_jbmr3608-bib-0024","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1053\/j.ajkd.2014.09.014","article-title":"Vitamin K status and mortality after kidney transplantation: a cohort study","volume":"65","author":"Keyzer","year":"2015","journal-title":"Am J Kidney Dis"},{"issue":"12","key":"2024021014513164700_jbmr3608-bib-0025","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.3390\/nu9121334","article-title":"Prevalence and effects of functional vitamin K insufficiency: the PREVEND Study","volume":"9","author":"Riphagen","year":"2017","journal-title":"Nutrients"},{"issue":"2","key":"2024021014513164700_jbmr3608-bib-0026","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.maturitas.2013.10.008","article-title":"Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease","volume":"77","author":"van den Heuvel","year":"2014","journal-title":"Maturitas"},{"issue":"21","key":"2024021014513164700_jbmr3608-bib-0027","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1161\/CIRCULATIONAHA.116.027011","article-title":"Slower progress of aortic valve calcification with vitamin K supplementation: results from a prospective interventional proof-of-concept study","volume":"135","author":"Brandenburg","year":"2017","journal-title":"Circulation"},{"issue":"9","key":"2024021014513164700_jbmr3608-bib-0028","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1111\/jth.13052","article-title":"Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis","volume":"13","author":"Veronese","year":"2015","journal-title":"J Thromb Haemost"},{"key":"2024021014513164700_jbmr3608-bib-0029","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bone.2015.05.046","article-title":"New insights into the biology of osteocalcin","volume":"82","author":"Zoch","year":"2016","journal-title":"Bone"},{"issue":"7","key":"2024021014513164700_jbmr3608-bib-0030","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/jbmr.2463","article-title":"Osteoblast-specific gamma-glutamyl carboxylase-deficient mice display enhanced bone formation with aberrant mineralization","volume":"30","author":"Azuma","year":"2015","journal-title":"J Bone Miner Res"},{"issue":"5","key":"2024021014513164700_jbmr3608-bib-0031","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.3892\/etm.2017.4206","article-title":"Level of serum undercarboxylated osteocalcin correlates with bone quality assessed by calcaneal quantitative ultrasound sonometry in young Japanese females","volume":"13","author":"Suzuki","year":"2017","journal-title":"Exp Ther Med"},{"issue":"45","key":"2024021014513164700_jbmr3608-bib-0032","doi-asserted-by":"crossref","first-page":"43919","DOI":"10.1074\/jbc.M303136200","article-title":"Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR","volume":"278","author":"Tabb","year":"2003","journal-title":"J Biol Chem"},{"issue":"2","key":"2024021014513164700_jbmr3608-bib-0033","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00198-015-3233-8","article-title":"Inflammation and the bone-vascular axis in end-stage renal disease","volume":"27","author":"Viaene","year":"2016","journal-title":"Osteoporos Int"},{"issue":"4","key":"2024021014513164700_jbmr3608-bib-0034","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1017\/S0007114508921760","article-title":"Vitamin K status is associated with childhood bone mineral content","volume":"100","author":"van Summeren","year":"2008","journal-title":"Br J Nutr"},{"key":"2024021014513164700_jbmr3608-bib-0035","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/1471-2369-13-134","article-title":"Pro-inflammatory cytokines and bone fractures in CKD patients. An exploratory single centre study","volume":"13","author":"Panuccio","year":"2012","journal-title":"BMC Nephrol"},{"issue":"1","key":"2024021014513164700_jbmr3608-bib-0036","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.kint.2017.04.006","article-title":"Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters","volume":"92","author":"Ketteler","year":"2017","journal-title":"Kidney Int"},{"issue":"3","key":"2024021014513164700_jbmr3608-bib-0037","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.maturitas.2013.11.002","article-title":"Effects of vitamin K in postmenopausal women: mini review","volume":"77","author":"Guralp","year":"2014","journal-title":"Maturitas"},{"issue":"3","key":"2024021014513164700_jbmr3608-bib-0038","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00198-014-2989-6","article-title":"Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials","volume":"26","author":"Huang","year":"2015","journal-title":"Osteoporos Int"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.3608","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbmr.3608","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbmr.3608","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/34\/2\/262\/56656071\/jbmr3608.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/34\/2\/262\/56656071\/jbmr3608.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:02:57Z","timestamp":1710342177000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/34\/2\/262-269\/7606033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,11,14]]},"published-print":{"date-parts":[[2019,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.3608","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,2,1]]},"published":{"date-parts":[[2018,11,14]]},"assertion":[{"value":"2018-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}