{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:12:23Z","timestamp":1779293543905,"version":"3.51.4"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":1944,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T00:00:00Z","timestamp":1543190400000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007903","name":"Bloodwise","doi-asserted-by":"publisher","award":["12053"],"award-info":[{"award-number":["12053"]}],"id":[{"id":"10.13039\/501100007903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Multiple myeloma is a plasma cell malignancy, which develops in the bone marrow and frequently leads to severe bone destruction. Current antiresorptive therapies to treat the bone disease do little to repair damaged bone; therefore, new treatment strategies incorporating bone anabolic therapies are urgently required. We hypothesized that combination therapy using the standard of care antiresorptive zoledronic acid (Zol) with a bone anabolic (anti-TGF\u03b2\/1D11) would be more effective at treating myeloma-induced bone disease than Zol therapy alone. JJN3 myeloma-bearing mice (n\u2009=\u20098\/group) treated with combined Zol and 1D11 resulted in a 48% increase (p\u2009\u2264\u20090.001) in trabecular bone volume (BV\/TV) compared with Zol alone and a 65% increase (p\u2009\u2264\u20090.0001) compared with 1D11 alone. Our most significant finding was the substantial repair of U266-induced osteolytic bone lesions with combination therapy (n\u2009=\u20098\/group), which resulted in a significant reduction in lesion area compared with vehicle (p\u2009\u2264\u20090.01) or Zol alone (p\u2009\u2264\u20090.01). These results demonstrate that combined antiresorptive and bone anabolic therapy is significantly more effective at preventing myeloma-induced bone disease than Zol alone. Furthermore, we demonstrate that combined therapy is able to repair established myelomatous bone lesions. This is a highly translational strategy that could significantly improve bone outcomes and quality of life for patients with myeloma. \u00a9 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3606","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T15:51:47Z","timestamp":1539618707000},"page":"783-796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Preventing and Repairing Myeloma Bone Disease by Combining Conventional Antiresorptive Treatment With a Bone Anabolic Agent in Murine Models"],"prefix":"10.1093","volume":"34","author":[{"given":"Julia","family":"Paton-Hough","sequence":"first","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Tazzyman","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Evans","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Lath","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny M","family":"Down","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alanna C","family":"Green","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Snowden","sequence":"additional","affiliation":[{"name":"Department of HaematologySheffield Teaching Hospitals NHS Foundation TrustRoyal Hallamshire HospitalSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D","family":"Chantry","sequence":"additional","affiliation":[{"name":"Department of HaematologySheffield Teaching Hospitals NHS Foundation TrustRoyal Hallamshire HospitalSheffieldUK"},{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology and Metabolism, Medical SchoolUniversity of SheffieldSheffieldUK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A","family":"Lawson","sequence":"additional","affiliation":[{"name":"Mellanby Centre for Bone ResearchUniversity of Sheffield Medical School, University of SheffieldSheffieldUK"},{"name":"Sheffield Myeloma Research TeamDepartment of Oncology 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