Increased bone remodeling due to ovariectomy dramatically increases tumoral growth in the 5T2 multiple myeloma mouse model

Abstract

Bone destruction is the main clinical consequence of multiple myeloma (MM). It is known that a “vicious circle” exists between bone and myeloma cells with plasma cells stimulating bone cells, which in return stimulate the neoplastic growth. We hypothesized that an accelerated bone remodeling induced by ovariectomy (OVX) could provide a more fertile environment for the myeloma cell growth. Ovariectomy performed on C57BL/KaLwRij mice resulted in reduced trabecular bone volume and increased osteoclast number. To test our hypothesis, we ovariectomized C57BL/KaLwRij mice one week before injection of 5T2MM myeloma cells. A non-OVX 5T2MM group was used as control. Ovariectomy increased the tumor growth and induced an earlier development of osteolytic lesions. OVX 5T2MM mice were euthanazied at 10 weeks, instead of 16 weeks, for the non-OVX 5T2MM, mice because of the accelerated development of disease in OVX animals. Treatment of OVX 5T2MM mice with pamidronate reduced osteolysis but had little effect on the time development of the tumor. This combined model (ovariectomy + 5T2MM) confirmed the interdependence of bone and myeloma cells and could explain the some sudden burden of indolent MM into aggressive MM in humans.