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Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice
Fumihito Kasama1, Hiroyuki Tsuchie2, Hiroyuki Nagasawa2
1Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan fumihito.kasama@med.akita-u.ac.jp.
Background/Aim:
This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma.
Materials And Methods:
CCRF S-180II cells (2-4×105 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed.
Results:
Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS.
Conclusion:
The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.
