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

Autor:	Paton-Hough J; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK., Tazzyman S; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK., Evans H; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK., Lath D; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK., Down JM; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK., Green AC; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK., Snowden JA; Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK., Chantry AD; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK.; Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK., Lawson MA; Sheffield Myeloma Research Team, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.; Mellanby Centre for Bone Research, University of Sheffield Medical School, University of Sheffield, Sheffield, UK.
Jazyk:	angličtina
Zdroj:	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research [J Bone Miner Res] 2019 May; Vol. 34 (5), pp. 783-796. Date of Electronic Publication: 2018 Nov 26.
DOI:	10.1002/jbmr.3606
Abstrakt:	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.)
Databáze:	MEDLINE
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