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Updated: Jul 9, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Zoledronic acid inhibits osteosarcoma growth in an orthotopic model
Crispin R Dass1, Peter F M Choong
1Department of Orthopaedics, St. Vincent's Hospital Melbourne, P.O. Box 2900, Fitzroy 3065, Melbourne, Australia. crispin.dass@svhm.org.au
Abstract:
Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. Its efficacy in osteosarcoma has not been convincingly proved in a clinically relevant model for the disease. In vitro, ZOL decreased osteosarcoma cell proliferation, mainly due to an increase in apoptosis in a dose-dependent fashion. There was a decrease in cell migration at >or=10 micromol/L concentrations, but invasion was inhibited at a much lower dose of 0.1 micromol/L. Reverse transcription-PCR showed that ZOL overall caused an increased expression of osteocalcin and decreased expression of alkaline phosphatase, osteopontin, osteonectin, and vascular endothelial growth factor, with no change in expression of osteoprotegerin. ZOL administration s.c. twice weekly at 0.12 mg/kg to SaOS-2 tumor-bearing mice resulted in primary tumor growth inhibition, reduction in lung metastases, and dramatic decrease in osteolysis. Furthermore, in the ZOL cohort, there was a clear reduction in the number of osteoclasts in bone exposed to tumor and a lower tumor vessel density. These data point to the adjuvant potential of ZOL in the management of osteosarcoma not only for its antiosteolytic properties but also for its ability to directly halt tumor cell growth and metastasis via its effects on viability, invasion, differentiation, and angiogenesis.
Insights
Zoledronic acid (ZOL) effectively inhibits osteosarcoma growth, invasion, and metastasis in preclinical models. It also reduces osteolysis and tumor angiogenesis, suggesting its potential as an adjuvant therapy.
Area of Science:
- Oncology
- Pharmacology
- Bone Biology
Background:
- Osteosarcoma is a primary bone cancer with significant metastatic potential.
- Osteolysis, bone destruction, is a hallmark of bone metastasis and can exacerbate disease progression.
- Zoledronic acid (ZOL) is a bisphosphonate known to inhibit osteoclast activity and reduce bone resorption.
Purpose of the Study:
- To evaluate the efficacy of Zoledronic acid (ZOL) in a preclinical model of osteosarcoma.
- To investigate the direct effects of ZOL on osteosarcoma cell behavior, including proliferation, migration, and invasion.
- To assess the impact of ZOL on osteolysis, metastasis, and angiogenesis in vivo.
Main Methods:
- In vitro studies assessed ZOL's effects on osteosarcoma cell proliferation, apoptosis, migration, and invasion.
- Reverse transcription-PCR analyzed gene expression changes in response to ZOL.
- In vivo studies involved administering ZOL to SaOS-2 tumor-bearing mice to evaluate tumor growth, metastasis, osteolysis, osteoclast number, and tumor vessel density.
Main Results:
- Zoledronic acid (ZOL) decreased osteosarcoma cell proliferation and increased apoptosis in vitro.
- ZOL inhibited cell invasion at low concentrations (0.1 µmol/L) and migration at higher concentrations (≥10 µmol/L).
- In vivo, ZOL reduced primary tumor growth, lung metastases, osteolysis, osteoclast numbers, and tumor angiogenesis, while altering expression of key bone remodeling and angiogenesis genes.
Conclusions:
- Zoledronic acid (ZOL) demonstrates significant anti-tumor and anti-metastatic effects in osteosarcoma preclinical models.
- ZOL exhibits direct anti-proliferative and anti-invasive properties against osteosarcoma cells.
- These findings support the potential of Zoledronic acid (ZOL) as an adjuvant therapy for osteosarcoma, targeting both tumor progression and bone destruction.
