Multiple myeloma is characterized by the growth of plasma cells in the bone marrow and the development of osteolytic
bone disease. Myeloma cells are found closely associated with bone, and targeting this environment may therefore affect both the
bone disease and the growth of myeloma cells. We have investigated the effect of the potent
bisphosphonate,
zoledronic acid, on the development of
bone disease,
tumor burden, and disease-free survival in the 5T2MM model of myeloma. 5T2MM murine myeloma cells were injected intravenously into C57BL/KaLwRij mice. After 8 weeks, all animals had a
paraprotein. Animals were treated with
zoledronic acid (120 microg/kg, subcutaneously, twice weekly) or vehicle, from the time of
tumor cell injection or from
paraprotein detection for 12 or 4 weeks, respectively. All animals injected with
tumor cells developed osteolytic lesions, a decrease in cancellous bone volume, an increase in osteoclast perimeter, and a decrease in bone mineral density.
Zoledronic acid prevented the formation of lesions, prevented cancellous bone loss and loss of bone mineral density, and reduced osteoclast perimeter.
Zoledronic acid also decreased
paraprotein concentration, decreased
tumor burden, and reduced angiogenesis. In separate experiments, Kaplan-Meier analysis demonstrated a significant increase in survival
after treatment with
zoledronic acid when compared with control (47 vs. 35 days). A single dose of
zoledronic acid was also shown to be effective in preventing the development of osteolytic
bone disease. These data show that
zoledronic acid is able to prevent the development of osteolytic
bone disease, decrease
tumor burden in bone, and increase survival in a model of established myeloma.