{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T20:19:53Z","timestamp":1775679593597,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,5,23]],"date-time":"2006-05-23T00:00:00Z","timestamp":1148342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold>  <jats:italic>Objectives<\/jats:italic>:\u2002Myeloma bone disease is a result of excessive osteoclast activation and impaired osteoblast function. Recent <jats:italic>in vitro<\/jats:italic> studies suggested that proteasome inhibitors might increase osteoblast function. <jats:italic>Methods<\/jats:italic>:\u2002We analyzed serum markers of osteoblast activity in 25 patients with multiple myeloma receiving bortezomib alone or in combination with dexamethasone. As control, serum samples from 58 consecutive myeloma patients receiving a therapy different than bortezomib (i.e. adriamycin\/dexamethasone, melphalan\/prednisone or thalidomide) were evaluated. The serum concentrations of bone\u2010specific alkaline phosphatase (BAP) and osteocalcin were quantified before initiation of treatment and after 3\u2003months. <jats:italic>Results<\/jats:italic>:\u2002In patients treated with bortezomib, mean serum levels of osteocalcin significantly increased from 6.3 to 10.8\u2003<jats:italic>\u03bc<\/jats:italic>g\/L (<jats:italic>P<\/jats:italic>\u2003=\u20030.024), while mean BAP levels increased from 19.7 to 30.2\u2003U\/L (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.0005). Of interest, the increase in BAP was significant both in responders and non\u2010responders. In contrast, the control group did not show a statistically significant change in BAP (24.8\u2003U\/L vs. 23.3\u2003U\/L) and osteocalcin (6.8\u2003<jats:italic>\u03bc<\/jats:italic>g\/L vs. 6.5\u2003<jats:italic>\u03bc<\/jats:italic>g\/L) before and after the treatment. <jats:italic>Conclusion<\/jats:italic>:\u2002These data show that treatment with bortezomib leads to enhanced markers of osteoblast activity in patients with myeloma. The comparison with the control group suggests that the effect on osteoblasts is unique to the proteasome inhibitor.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2006.00692.x","type":"journal-article","created":{"date-parts":[[2006,5,23]],"date-time":"2006-05-23T14:46:33Z","timestamp":1148395593000},"page":"233-238","source":"Crossref","is-referenced-by-count":131,"title":["Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment"],"prefix":"10.1111","volume":"77","author":[{"given":"Ulrike","family":"Heider","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Jakob","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Zavrski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten\u2010Oliver","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Fleissner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Hecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orhan","family":"Sezer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,5,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041875"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.041131"},{"key":"e_1_2_6_4_2","first-page":"3047","article-title":"Serum levels of carboxy\u2010terminal telopeptide of type\u2010I collagen are elevated in patients with multiple myeloma showing skeletal manifestations in magnetic resonance imaging but lacking lytic bone lesions in conventional radiography","volume":"9","author":"Jakob C","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(97)10133-2"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197411142912001"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-09-2684"},{"key":"e_1_2_6_8_2","first-page":"5438","article-title":"Receptor activator of nuclear factor\u2010kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo","volume":"63","author":"Farrugia AN","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05018.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-12-3905"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1687"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0148"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.1.353"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-004-0578-3"},{"key":"e_1_2_6_15_2","first-page":"1436","article-title":"Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma","volume":"9","author":"Heider U","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115305"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.1992.tb00514.x"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0609.2000.065005331.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.1042920.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00298552"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403423"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16198"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-200506000-00002"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.030"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-003-0454-6"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00930.x"},{"key":"e_1_2_6_27_2","first-page":"394","article-title":"Biochemical markers of bone disease in asymptomatic early stage multiple myeloma. 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