Research Papers:

Can Denosumab be used in combination with Doxorubicin in Osteosarcoma?

Francesca Punzo _, Chiara Tortora, Maura Argenziano, Daniela Di Pinto, Elvira Pota, Martina Di Martino, Alessandra Di Paola and Francesca Rossi

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Oncotarget. 2020; 11:2763-2773. https://doi.org/10.18632/oncotarget.27669

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Francesca Punzo1,2, Chiara Tortora1, Maura Argenziano2, Daniela Di Pinto1, Elvira Pota1, Martina Di Martino1, Alessandra Di Paola2 and Francesca Rossi1

1 Department of Woman, Child and General and Specialist Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

2 Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy

Correspondence to:

Francesca Punzo,email: [email protected]

Keywords: osteosarcoma; Denosumab; Doxorubicin; RANK-L; bone mass loss

Received: April 08, 2020     Accepted: June 20, 2020     Published: July 14, 2020


Osteosarcoma is an aggressive bone tumor of the pediatric age. It is therefore important to improve conventional therapies (chemotherapy and surgery). Anticancer drugs often cause osteoporosis due to a misbalance of RANK/RANK-L/OPG pathway.

Denosumab is a monoclonal antibody with high affinity and specificity to RANK-L, the ligand released by osteoblasts that enhances osteoclasts differentiation and bone resorption. It is used in osteoporosis and in other conditions characterized by bone mass loss. Doxorubicin is a chemotherapic drug used in several kinds of tumors, and also patients treated with it often develop osteoporosis.

We investigated the effects of Denosumab alone and in combination with Doxorubicin, in two human osteosarcoma cell lines (MG63 and U-2 OS). We evaluated the effect of these treatments on apoptosis, cell cycle progression, invasion capacity and bone metabolism.

We observed for the first time an anti-invasive effect of Denosumab in OS cells and confirmed its anti-osteoporotic activity also in Osteosarcoma. On the other hand, we demonstrate that Denosumab not only does not affect apoptosis and cell cycle progression, but when used in combination with Doxorubicin, it causes an unexpected reduction of its activity. These results indicate that the presence of Denosumab might inhibit the efficacy of the chemotherapic drug.

In conclusion, while our results certainly support and confirm the efficacy of Denosumab in Osteoporosis, we discourage the use of Denosumab in addition to conventional chemotherapy in Osteosarcoma, even though, certainly further investigations are necessary to better clarify the clinical role of this monoclonal antibody in cancer.

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