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

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-TGF?/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.

SUBMITTER: Paton-Hough J

PROVIDER: S-EPMC6607020 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Paton-Hough Julia J Tazzyman Simon S Evans Holly H Lath Darren D Down Jenny M JM Green Alanna C AC Snowden John A JA Chantry Andrew D AD Lawson Michelle A MA

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20181126 5

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 my ...[more]

PMID: 30320927

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Project description:Background and objectivesIt remains unknown whether the combination of antiresorptive agents and exercise would generate additive effects on bone mineral density (BMD) in postmenopausal women, though their separate roles in preventing bone loss have been well established. This meta-analysis aimed to evaluate the combined impact of antiresorptive treatment and exercise on the lumbar spine and femoral neck BMD in postmenopausal women compared with an exercise-only intervention.MethodsA systematic literature search of PubMed, EMBASE, SportDiscus and ProQuest up to Jun 2014 was conducted to identify the influence of antiresorptive agents and exercise on BMD in postmenopausal women. The study quality of the included trials was evaluated. The effect sizes were estimated by calculating the standardized mean difference (SMD). Subgroup analyses were conducted by pharmacological regimens and exercise categories.ResultsNine studies with a total of 1,248 postmenopausal women met the inclusion criteria. The heterogeneity between the studies was evident at the spine (I² = 78.7%) and hip (I² = 41.7%) measurements; random-effects models were used in the data analysis. The pooled effect sizes associated with the combined interventions of antiresorptive agents and exercise were significant at the lumbar spine BMD (SMD = 0.511, 95% CI = 0.118-0.904, p = 0.011). Combining hormone replacement therapy (HRT) and exercise training generated greater beneficial effects on lumbar spine (SMD = 0.729, 95% CI = 0.186-1.273, p = 0.009) and femoral neck BMD (SMD = 0.220, 95% CI = 0.0110-429, p = 0.039) than the exercise-only intervention. Impact exercise was sensitive to antiresorptive agents in preventing postmenopausal bone loss both at the spine (SMD = 1.252, 95%CI = 0.465-2.039, p = 0.002) and hips (SMD = 0.414, 95%CI = 0.106-0.723, p = 0.008).ConclusionsOur findings indicate that antiresorptive agents significantly increase the impact of exercise on the prevention of bone loss in postmenopausal women, which implies that the combination of antiresorptive agents and exercise may generate additive effects.

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Dataset Information

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

Publications

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

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