Title:The Role of Mifamurtide in Chemotherapy-induced Osteoporosis of Children with Osteosarcoma
Volume: 17
Issue: 7
Author(s): Giulia Bellini, Daniela Di Pinto, Chiara Tortora, Iolanda Manzo, Francesca Punzo, Fiorina Casale and Francesca Rossi*
Affiliation:
- Department of Women, Child and General and Specialist Surgery, The Second University of Naples, via Luigi De Crecchio, 4 - 80138 Naples,Italy
Keywords:
Osteosarcoma-associated bone loss, resorption, osteoclast activation, tumor outcome, cancer associated disease,
osteosarcoma follow-up.
Abstract: Background: Osteosarcoma is the most frequent malignant bone tumor in childhood and
young adulthood. Long-term survivors of osteosarcoma patients show high prevalence of osteoporosis
and fractures. The immunomodulatory mifamurtide, which modulates macrophages activity, improves
disease outcome.
Objective: To evaluate the role of mifamurtide on macrophage component of bone, the osteoclasts,
during chemotherapy in children with osteosarcoma.
Method: Osteoclasts, obtained from peripheral blood cells of healthy donors were harvested in the
presence or not of mifamurtide. Moreover, osteoclast cultures were obtained from osteosarcoma patients,
at onset and during chemotherapy, alone or with mifamurtide. Pro-osteoporotic tartrateresistant
acid phosphatase (TRAP), phosphokinase-β-2 (PKCβ2), vanilloid receptor type 1 (TRPV1),
and anti-osteoporotic cannabinoid receptor type 2 (CB2) biomarkers were analyzed by bio-molecular
(qPCR), biochemical (Western Blotting), and morphological (TRAP assay) approaches.
Results: Osteoclasts from osteosarcoma patients show significant increase of TRAP and decrease of
CB2 with respect to osteoclasts from healthy donors. This osteoclast hyperactivity is more evident in
osteoclasts from osteosarcoma patients during chemotherapy. Mifamurtide reduces pro-osteoporotic
TRAP, PKCβ2, TRPV1 levels and increases CB2 in osteoclasts from healthy donors. Moreover,
chemotherapy-induced effects on bone resorption markers are fully reverted in osteoclasts derived
from osteosarcoma patients in chemotherapy plus mifamurtide.
Conclusion: Our data suggest a new therapeutic role for mifamurtide as possible anti-resorption agent
in chemotherapy-induced osteoporosis in children with osteosarcoma.
