{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T12:03:04Z","timestamp":1782216184411,"version":"3.54.5"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Support Care Cancer"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose\n<\/jats:title>\n                <jats:p>Peripheral neuropathy (PN) is common in multiple myeloma (MM) patients. More insight has been gained concerning the role of vitamin D in preventing PN. However, studies evaluating the effects of vitamin D<jats:sub>3<\/jats:sub> supplementation on PN are lacking. The aims of this study are to (1) evaluate the effectiveness of a vitamin D<jats:sub>3<\/jats:sub> regimen on achieving adequate vitamin D levels in deficient MM patients and to (2) exploratively evaluate the effect of vitamin D<jats:sub>3<\/jats:sub> supplementation on PN.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Thirty-nine MM patients with inadequate (&lt;\u200975\u00a0nmol\/L [=\u200930\u00a0ng\/mL]) 25-hydroxyvitamin D (25(OH)D) levels were included in this multicenter, prospective, single-arm study, of whom 35 patients completed the study. They received oral vitamin D<jats:sub>3<\/jats:sub> for 6\u00a0months according to a dose escalation regimen that consisted of one or two loading doses of 200,000 international units (IU), and maintenance doses of 800, 1600, or 3200\u00a0IU\/day depending on the 25(OH)D level. A validated questionnaire was used to measure PN.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Median 25(OH)D increased from 38 (IQR 32\u201352) nmol\/L at baseline to 77 (IQR 72\u201387) nmol\/L after 6\u00a0months (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Adequate 25(OH)D levels were achieved by 66% of the subjects, and 34% were within the range of 50\u201375\u00a0nmol\/L. Furthermore, in 37% of the participants, PN severity decreased (<jats:italic>P<\/jats:italic>\u2009=\u20090.007).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The use of substantially higher vitamin D<jats:sub>3<\/jats:sub> doses than recommended in current guidelines resulted in a significant increase in vitamin D levels in MM patients. Furthermore, evaluation of PN showed a significant decrease in PN grading. However, this exploratory evaluation needs further confirmatory research.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00520-023-07574-0","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T07:02:36Z","timestamp":1674716556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effectiveness of a vitamin D regimen in deficient multiple myeloma patients and its effect on peripheral neuropathy"],"prefix":"10.1007","volume":"31","author":[{"given":"Berdien E.","family":"Oortgiesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marloes","family":"Dekens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud","family":"Stapel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrazzaq","family":"Alheraky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline de Keizer","family":"Dannenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Siemes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G. A.","family":"Jansman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robby E.","family":"Kibbelaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nic J. G. M.","family":"Veeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mels","family":"Hoogendoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric N.","family":"van Roon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"7574_CR1","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1002\/Ajh.25791","volume":"95","author":"SV Rajkumar","year":"2020","unstructured":"Rajkumar SV (2020) Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol 95:548\u2013567. https:\/\/doi.org\/10.1002\/Ajh.25791","journal-title":"Am J Hematol"},{"key":"7574_CR2","doi-asserted-by":"publisher","first-page":"117822421986823","DOI":"10.1177\/1178224219868235","volume":"13","author":"SA Bird","year":"2019","unstructured":"Bird SA, Boyd K (2019) Multiple myeloma: an overview of management. Palliat Care Soc Pract 13:1178224219868235. https:\/\/doi.org\/10.1177\/1178224219868235","journal-title":"Palliat Care Soc Pract"},{"key":"7574_CR3","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1016\/J.Jcot.2019.07.004","volume":"10","author":"N Charoenngam","year":"2019","unstructured":"Charoenngam N, Shirvani A, Mf H (2019) Vitamin D for skeletal and non-skeletal health: what we should know. J Clin Orthop Trauma 10:1082\u20131093. https:\/\/doi.org\/10.1016\/J.Jcot.2019.07.004","journal-title":"J Clin Orthop Trauma"},{"key":"7574_CR4","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1210\/Er.2012-1000","volume":"33","author":"CJ Rosen","year":"2012","unstructured":"Rosen CJ, Adams JS, Bikle DD, Black DM, Demay MB, Manson JE, Murad MH, Kovacs CS (2012) The nonskeletal effects of vitamin D: an Endocrine Society Scientific Statement. Endocr Rev 33:456\u2013492. https:\/\/doi.org\/10.1210\/Er.2012-1000","journal-title":"Endocr Rev"},{"key":"7574_CR5","doi-asserted-by":"publisher","first-page":"E2025850","DOI":"10.1001\/Jamanetworkopen.2020.25850","volume":"3","author":"Chandler PD, Chen WY, Ajala On, Hazra A, Cook N, Bubes V, Lee IM, Giovannucci El, Willett W, Buring JE, Manson JE, Vital Research Group","year":"2020","unstructured":"Chandler PD, Chen WY, Ajala On, Hazra A, Cook N, Bubes V, Lee IM, Giovannucci El, Willett W, Buring JE, Manson JE, Vital Research Group (2020) Effect of vitamin D3 supplements on development of advanced cancer: a secondary analysis of the VITAL randomized clinical trial. Jama Netw Open 3:E2025850. https:\/\/doi.org\/10.1001\/Jamanetworkopen.2020.25850","journal-title":"Jama Netw Open"},{"key":"7574_CR6","doi-asserted-by":"publisher","unstructured":"Wang J, Udd KA, Vidisheva A, Swift RA, Spektor TM, Bravin E, Ibrahim E, Treisman J, Masri M, Berenson Jr (2016) Low serum vitamin D occurs commonly among multiple myeloma patients treated with bortezomib and\/or thalidomide and is associated with severe neuropathy. Support Care Cancer 24:3105-3110. https:\/\/doi.org\/10.1007\/S00520-016-3126-1","DOI":"10.1007\/S00520-016-3126-1"},{"key":"7574_CR7","doi-asserted-by":"publisher","DOI":"10.1007\/S00520-019-04942-7","author":"K Nath","year":"2019","unstructured":"Nath K, Ganeshalingam V, Ewart B, Heyer E, Watt K, Birchley A, Casey J, Lai HC, Morris E, Hodges G (2019) A retrospective analysis of the prevalence and clinical outcomes of vitamin D deficiency in myeloma patients in tropical Australia. Support Care Cancer. https:\/\/doi.org\/10.1007\/S00520-019-04942-7","journal-title":"Support Care Cancer"},{"key":"7574_CR8","doi-asserted-by":"publisher","first-page":"300060520943421","DOI":"10.1177\/0300060520943421","volume":"48","author":"V Graklanov","year":"2020","unstructured":"Graklanov V, Popov V (2020) Vitamin D levels in patients with non-Hodgkin lymphoma\/diffuse large B-cell lymphoma, chronic lymphocytic leukemia and multiple myeloma. J Int Med Res 48:300060520943421. https:\/\/doi.org\/10.1177\/0300060520943421","journal-title":"J Int Med Res"},{"key":"7574_CR9","doi-asserted-by":"publisher","DOI":"10.1111\/Bjh.16674","author":"\u00c3 Langseth","year":"2020","unstructured":"Langseth \u00c3, Myklebust T, Johannesen TB, Hjertner \u00c3, Waage A (2020) Incidence and survival of multiple myeloma: a population-based study of 10\u00e2 524 patients diagnosed 1982\u20132017. Br J Haematol. https:\/\/doi.org\/10.1111\/Bjh.16674","journal-title":"Br J Haematol"},{"key":"7574_CR10","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/J.1529-8027.2008.00193.X","volume":"13","author":"V Chaudhry","year":"2008","unstructured":"Chaudhry V, Dr C, Polydefkis M, Ferguson A, Borrello I (2008) Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. J Peripher Nerv Syst 13:275\u2013282. https:\/\/doi.org\/10.1111\/J.1529-8027.2008.00193.X","journal-title":"J Peripher Nerv Syst"},{"key":"7574_CR11","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1212\/01.wnl.0000267271.18475.fe","volume":"69","author":"R Plasmati","year":"2007","unstructured":"Plasmati R, Pastorelli F, Cavo M, Petracci E, Zamagni E, Tosi P, Cangini D, Tacchetti P, Salvi F, Bartolomei I, Michelucci R, Tassinari CA (2007) Neuropathy in multiple myeloma treated with thalidomide: a prospective study. Neurology 69:573\u2013581","journal-title":"Neurology"},{"key":"7574_CR12","doi-asserted-by":"publisher","first-page":"3518","DOI":"10.1200\/Jco.2008.18.3087","volume":"27","author":"PG Richardson","year":"2009","unstructured":"Richardson PG, Xie W, Mitsiades C, Chanan-Khan AA, Lonial S, Hassoun H, Avigan DE, Oaklander AL, Kuter DJ, Wen PY, Kesari S, Briemberg HR, Schlossman RL, Munshi NC, Heffner LT, Doss D, Esseltine DL, Weller E, Anderson KC, Amato AA (2009) Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol 27:3518\u20133525. https:\/\/doi.org\/10.1200\/Jco.2008.18.3087","journal-title":"J Clin Oncol"},{"key":"7574_CR13","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1007\/S10072-016-2542-9","volume":"37","author":"C Leone","year":"2016","unstructured":"Leone C, Federico V, La Cesa S, Russo E, Di Stefano G, Finsinger P, Labriola R, Cruccu G, Petrucci MT, Truini A\u00a0(2016) An observational study assessing peripheral neuropathy related to multiple myeloma. Neurol Sci 37:1141\u20131143. https:\/\/doi.org\/10.1007\/S10072-016-2542-9","journal-title":"Neurol Sci"},{"key":"7574_CR14","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.beha.2005.01.024","volume":"18","author":"A Dispenzieri","year":"2005","unstructured":"Dispenzieri A, Kyle RA\u00a0(2005) Neurological aspects of multiple myeloma and related disorders. Best Pract Res Clin Haematol 18:673\u2013688","journal-title":"Best Pract Res Clin Haematol"},{"key":"7574_CR15","doi-asserted-by":"publisher","DOI":"10.1007\/S00520-021-06414-3","author":"O Be","year":"2021","unstructured":"Oortgiesen BE, Kroes JA, Scholtens P, Hoogland J, Dannenberg-de Keijzer P, Siemes C, Jansman FGA, Kibbelaar RE, Veeger NJGM, Hoogendoorn M, van Roon EN (2021)\u00a0High prevalence of peripheral neuropathy in multiple myeloma patients and the impact of vitamin D levels, a cross-sectional study. Support Care Cancer. https:\/\/doi.org\/10.1007\/S00520-021-06414-3","journal-title":"Support Care Cancer"},{"key":"7574_CR16","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1007\/s001250051443","volume":"42","author":"S Riaz","year":"1999","unstructured":"Riaz S, Malcangio M, Miller M, Tomlinson DR\u00a0(1999) A vitamin D(3) derivative (Cb1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats. Diabetologia 42:1308\u20131313","journal-title":"Diabetologia"},{"key":"7574_CR17","doi-asserted-by":"publisher","first-page":"E0183491","DOI":"10.1371\/Journal.Pone.0183491","volume":"12","author":"J Youk","year":"2017","unstructured":"Youk J, Kim YS, Lim JA, Shin DY, Koh Y, Lee ST, Kim I(2017) Depletion of nerve growth factor in chemotherapy-induced peripheral neuropathy associated with hematologic malignancies. PLoS ONE 12:E0183491. https:\/\/doi.org\/10.1371\/Journal.Pone.0183491","journal-title":"PLoS ONE"},{"key":"7574_CR18","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1523\/JNEUROSCI.21-01-00098.2001","volume":"21","author":"Ld Brewer","year":"2001","unstructured":"Brewer LD, Thibault V, Chen KC, Langub MC, Landfield PW, Porter NM\u00a0(2001) Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. J Neurosci 21:98\u2013108","journal-title":"J Neurosci"},{"key":"7574_CR19","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/S1043-2760(01)00547-1","volume":"13","author":"E Garcion","year":"2002","unstructured":"Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D\u00a0(2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 13:100\u2013105","journal-title":"Trends Endocrinol Metab"},{"key":"7574_CR20","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1023\/B:BIRY.0000040196.65686.2f","volume":"69","author":"K Av","year":"2004","unstructured":"Kalueff AV, Eremin KO, Tuohimaa P(2004) Mechanisms Of neuroprotective action of vitamin D(3). Biochemistry (Mosc) 69:738\u2013741","journal-title":"Biochemistry (Mosc)"},{"key":"7574_CR21","doi-asserted-by":"publisher","unstructured":"Vashi PG, Trukova K, Lammersfeld CA, Braun DP, Gupta D\u00a0(2010) Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology. Nutr J 9:60\u20132891\u20139\u201360. https:\/\/doi.org\/10.1186\/1475-2891-9-60","DOI":"10.1186\/1475-2891-9-60"},{"key":"7574_CR22","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1007\/S40266-018-0601-Z","volume":"35","author":"M Toren-Wielema","year":"2018","unstructured":"Toren-Wielema M, Veenhuizen R, Kappelle JW, Veeger N, van Roon E\u00a0(2018) Efficacy of a standardized oral vitamin D dosing regimen in nursing home residents. Drugs Aging 35:1079\u20131087. https:\/\/doi.org\/10.1007\/S40266-018-0601-Z","journal-title":"Drugs Aging"},{"key":"7574_CR23","doi-asserted-by":"publisher","first-page":"318","DOI":"10.3109\/09637486.2010.536146","volume":"62","author":"M Kc","year":"2011","unstructured":"Maki KC, Rubin MR, Wong LG, McManus JF, Jensen CD, Lawless A\u00a0(2011) Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference. Int J Food Sci Nutr 62:318\u2013327. https:\/\/doi.org\/10.3109\/09637486.2010.536146","journal-title":"Int J Food Sci Nutr"},{"key":"7574_CR24","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1056\/NEJMra070553","volume":"357","author":"H Mf","year":"2007","unstructured":"Holick MF\u00a0(2007) Vitamin D deficiency. N Engl J Med 357:266\u2013281","journal-title":"N Engl J Med"},{"key":"7574_CR25","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1210\/Jc.2011-0385","volume":"96","author":"Holick Mf, Binkley Nc, Bischoff-Ferrari Ha, Gordon Cm, Hanley Da, Heaney Rp, Murad Mh, Weaver Cm, Endocrine Society","year":"2011","unstructured":"Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society\u00a0(2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 96:1911\u20131930. https:\/\/doi.org\/10.1210\/Jc.2011-0385","journal-title":"J Clin Endocrinol Metab"},{"key":"7574_CR26","unstructured":"European Medicines Agency (May 24, 2019) Summary of product characteristics of colecalciferol. https:\/\/www.Medicines.Org.Uk\/Emc\/Product\/2382\/Smpc. Accessed January, 16 2020"},{"key":"7574_CR27","unstructured":"European Medicines Agency (September 28, 2018) Summary of product characteristics of colecalciferol oral solution. https:\/\/www.Ncbi.Nlm.Nih.Gov\/Pmc\/Articles\/Pmc4128480\/Pdf\/Nihms605790.Pdf 2020"},{"key":"7574_CR28","doi-asserted-by":"publisher","first-page":"2411","DOI":"10.1007\/S00520-015-3032-Y","volume":"24","author":"B Aj","year":"2016","unstructured":"Beijers AJ, Vreugdenhil G, Oerlemans S, Eurelings M, Minnema MC, Eeltink CM, van de Poll-Franse LV, Mols F\u00a0(2016) Chemotherapy-induced neuropathy in multiple myeloma: influence on quality of life and development of a questionnaire to compose common toxicity criteria grading for use in daily clinical practice. Support Care Cancer 24:2411\u20132420. https:\/\/doi.org\/10.1007\/S00520-015-3032-Y","journal-title":"Support Care Cancer"},{"key":"7574_CR29","unstructured":"Nhg-Standaard (2018) Laboratoriumdiagnostiek Vitamine D-Defici\u00ebntie. https:\/\/www.Nhg.Org\/Themas\/Publicaties\/Laboratoriumdiagnostiek-Vitamine-D--Deficientie-Volledige-Tekst. Accessed 1 Jan 2022"}],"container-title":["Supportive Care in Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00520-023-07574-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00520-023-07574-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00520-023-07574-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:23:37Z","timestamp":1676334217000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00520-023-07574-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["7574"],"URL":"https:\/\/doi.org\/10.1007\/s00520-023-07574-0","relation":{},"ISSN":["0941-4355","1433-7339"],"issn-type":[{"value":"0941-4355","type":"print"},{"value":"1433-7339","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]},"assertion":[{"value":"28 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Medical Centre Leeuwarden (No. NL64024.099.17).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Frank Jansman has received personal fees from Amgen and Genzyme for participation in advisory boards. The other authors have no conflicts of interest to declare that are relevant to the content of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"138"}}