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Preventing and Repairing Myeloma Bone Disease by Combining Conventional Antiresorptive Treatment With a Bone Anabolic Agent in Murine Models.

Authors
  • Paton-Hough, Julia1, 2
  • Tazzyman, Simon1, 2
  • Evans, Holly1, 2
  • Lath, Darren1, 2
  • Down, Jenny M1, 2
  • Green, Alanna C1, 2
  • Snowden, John A3
  • Chantry, Andrew D1, 2, 3
  • Lawson, Michelle A1, 2
  • 1 Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.
  • 2 Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK.
  • 3 Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK.
Type
Published Article
Journal
Journal of Bone and Mineral Research
Publisher
Wiley (John Wiley & Sons)
Publication Date
May 01, 2019
Volume
34
Issue
5
Pages
783–796
Identifiers
DOI: 10.1002/jbmr.3606
PMID: 30320927
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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-TGFβ/1D11) would be more effective at treating myeloma-induced bone disease than Zol therapy alone. JJN3 myeloma-bearing mice (n = 8/group) treated with combined Zol and 1D11 resulted in a 48% increase (p ≤ 0.001) in trabecular bone volume (BV/TV) compared with Zol alone and a 65% increase (p ≤ 0.0001) compared with 1D11 alone. Our most significant finding was the substantial repair of U266-induced osteolytic bone lesions with combination therapy (n = 8/group), which resulted in a significant reduction in lesion area compared with vehicle (p ≤ 0.01) or Zol alone (p ≤ 0.01). 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. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

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