Paton-Hough, J., Tazzyman, S., Evans, H. et al. (6 more authors) (2018) Preventing and repairing myeloma bone disease by combining conventional antiresorptive treatment with a bone anabolic agent in murine models. Journal of Bone and Mineral Research. ISSN 0884-0431
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 BV/TV compared to Zol alone and a 65% increase (p≤0.0001) compared to 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 to 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 which could significantly improve bone outcomes and quality of life for patients with myeloma.
Metadata
Authors/Creators: |
|
||||||
---|---|---|---|---|---|---|---|
Copyright, Publisher and Additional Information: | © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | ||||||
Dates: |
|
||||||
Institution: | The University of Sheffield | ||||||
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals | ||||||
Funding Information: |
|
||||||
Depositing User: | Symplectic Sheffield | ||||||
Date Deposited: | 31 Oct 2018 14:52 | ||||||
Last Modified: | 15 Oct 2019 00:39 | ||||||
Published Version: | https://doi.org/10.1002/jbmr.3606 | ||||||
Status: | Published online | ||||||
Publisher: | American Society for Bone and Mineral Research | ||||||
Refereed: | Yes | ||||||
Identification Number: | https://doi.org/10.1002/jbmr.3606 | ||||||
Related URLs: |
Downloads
Filename: jbmr.3606.pdf
Filename: Paton-Hough_et_al-2019-Journal_of_Bone_and_Mineral_Research.pdf
Licence: CC-BY-NC 4.0