Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106969
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Type: Journal article
Title: Combination breast cancer chemotherapy with doxorubicin and cyclophosphamide damages bone and bone marrow in a female rat model
Author: Fan, C.
Georgiou, K.
Morris, H.
McKinnon, R.
Keefe, D.
Howe, P.
Xian, C.
Citation: Breast Cancer Research and Treatment, 2017; 165(1):41-51
Publisher: Springer US
Issue Date: 2017
ISSN: 0167-6806
1573-7217
Statement of
Responsibility: 
Chiaming Fan, Kristen R. Georgiou, Howard A. Morris, Ross A. McKinnon, Dorothy M. K. Keefe, Peter R. Howe, Cory J. Xian
Abstract: Purpose: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. Methods: This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. Results: AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase. Reductions in densities of osteocytes and bone lining cells were also observed. In addition, bone marrow was severely damaged, including a severe reduction in bone marrow cellularity and an increase in marrow adipocyte content. Accompanying these changes, there were increases in mRNA expression of adipogenesis regulatory genes (PPARc and FABP4) and an inflammatory cytokine (TNFa) in metaphysis bone and bone marrow. Conclusions: This study indicates that AC chemotherapy may induce some bone loss, due to reduced bone formation, and bone marrow damage, due to increased marrow adiposity. Preventive strategies for preserving the bone and bone marrow microenvironment during anthracycline chemotherapy warrant further investigation.
Keywords: Breast cancer chemotherapy; Bone loss; Bone marrow adiposity; Bone marrow damage; Bone turnover; Osteoclasts
Description: Published online: 26 May 2017
Rights: © Springer Science+Business Media New York 2017
RMID: 0030071140
DOI: 10.1007/s10549-017-4308-3
Grant ID: http://purl.org/au-research/grants/nhmrc/1010752
http://purl.org/au-research/grants/arc/LP120100519
http://purl.org/au-research/grants/nhmrc/1042105
Appears in Collections:Medicine publications

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