Effects of Alendronate and Alfacalcidol on Preventing Bone Loss in Chemotherapy-treated Soft-tissue Sarcoma
- 1Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan
- 2Department of Orthopedic Surgery, Noshiro Kousei Medical Center, Akita, Japan
- 3Department of Orthopedic Surgery, Akita Rosai Hospital, Akita, Japan
Abstract
Background/Aim: Cancer treatment-induced bone loss (CTIBL) increases fracture risk and impairs quality of life, but little is known about CTIBL in soft-tissue sarcoma. This study aimed to investigate whether alendronate and alfacalcidol prevent doxorubicin-induced bone loss in a mouse model of soft-tissue sarcoma.
Materials and Methods: Sarcoma S-180II cells were transplanted subcutaneously into 10-week-old female BALB/c mice using an air-pouch model. After tumor engraftment, mice received weekly intraperitoneal doxorubicin and were allocated to one of four groups: vehicle control, alendronate, alfacalcidol, and alendronate plus alfacalcidol. Alendronate was administered subcutaneously twice weekly, and alfacalcidol was administered orally three times weekly. Mice were euthanized 2 or 4 weeks after tumor transplantation. Body weight, tumor weight and volume, femoral microstructure by micro-computed tomography, histomorphometric indices by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin immunostaining, and receptor activator of nuclear factor-κB ligand (RANKL) and runt-related transcription factor 2 (RUNX2) expression were evaluated.
Results: Body weight and tumor parameters did not differ among groups. At 2 weeks, combination therapy had significantly increased trabecular bone volume fraction, thickness, and number compared with the vehicle control. At 4 weeks, alendronate alone and combination therapy had preserved trabecular bone volume and number and reduced trabecular separation; combination therapy resulted in higher bone-volume fraction and trabecular number than alendronate alone. Cortical bone area and thickness were also greater in all drug-treated groups than in the control at 4 weeks. TRAP staining showed significant suppression of osteoclast-related indices in the alendronate- and combination-treated groups, whereas no significant differences were observed in osteocalcin, RANKL, or RUNX2 expression.
Conclusion: Alendronate may prevent doxorubicin-associated bone loss in soft-tissue sarcoma, primarily by directly suppressing residual osteoclast activity in vivo.
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BibTeX
@article{nakanishi2026effects,
title = {{Effects of Alendronate and Alfacalcidol on Preventing Bone Loss in Chemotherapy-treated Soft-tissue Sarcoma}},
author = {MANAMI NAKANISHI and HIROYUKI TSUCHIE and HIROYUKI NAGASAWA and MICHIO HONGO and YUJI KASUKAWA and KOJI NOZAKA and TAKASHI KAWARAGI and MANABU WATANABE and YASUHITO ASAKA and YO MORISHITA and NAOHISA MIYAKOSHI},
journal = {In Vivo},
year = {2026},
month = oct,
doi = {10.21873/invivo.14479},
url = {https://doi.org/10.21873/invivo.14479},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Effects of Alendronate and Alfacalcidol on Preventing Bone Loss in Chemotherapy-treated Soft-tissue Sarcoma
AU - MANAMI NAKANISHI
AU - HIROYUKI TSUCHIE
AU - HIROYUKI NAGASAWA
AU - MICHIO HONGO
AU - YUJI KASUKAWA
AU - KOJI NOZAKA
AU - TAKASHI KAWARAGI
AU - MANABU WATANABE
AU - YASUHITO ASAKA
AU - YO MORISHITA
AU - NAOHISA MIYAKOSHI
PY - 2026
DA - 2026/10/29
JO - In Vivo
DO - 10.21873/invivo.14479
UR - https://doi.org/10.21873/invivo.14479
AB - Background/Aim: Cancer treatment-induced bone loss (CTIBL) increases fracture risk and impairs quality of life, but little is known about CTIBL in soft-tissue sarcoma. This study aimed to investigate whether alendronate and alfacalcidol prevent doxorubicin-induced bone loss in a mouse model of soft-tissue sarcoma. Materials and Methods: Sarcoma S-180II cells were transplanted subcutaneously into 10-week-old female BALB/c mice using an air-pouch model. After tumor engraftment, mice received weekly intraperitoneal doxorubicin and were allocated to one of four groups: vehicle control, alendronate, alfacalcidol, and alendronate plus alfacalcidol. Alendronate was administered subcutaneously twice weekly, and alfacalcidol was administered orally three times weekly. Mice were euthanized 2 or 4 weeks after tumor transplantation. Body weight, tumor weight and volume, femoral microstructure by micro-computed tomography, histomorphometric indices by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin immunostaining, and receptor activator of nuclear factor-κB ligand (RANKL) and runt-related transcription factor 2 (RUNX2) expression were evaluated. Results: Body weight and tumor parameters did not differ among groups. At 2 weeks, combination therapy had significantly increased trabecular bone volume fraction, thickness, and number compared with the vehicle control. At 4 weeks, alendronate alone and combination therapy had preserved trabecular bone volume and number and reduced trabecular separation; combination therapy resulted in higher bone-volume fraction and trabecular number than alendronate alone. Cortical bone area and thickness were also greater in all drug-treated groups than in the control at 4 weeks. TRAP staining showed significant suppression of osteoclast-related indices in the alendronate- and combination-treated groups, whereas no significant differences were observed in osteocalcin, RANKL, or RUNX2 expression. Conclusion: Alendronate may prevent doxorubicin-associated bone loss in soft-tissue sarcoma, primarily by directly suppressing residual osteoclast activity in vivo.
SN - 0258-851X
SN - 1791-7549
ER -