Bone
metastases are common in many advanced
cancers and are a clinically relevant source of skeletal morbidity. The bone
mineral matrix contains numerous
growth factors that are released during normal bone remodeling, providing a fertile microenvironment for
tumor cell colonization and proliferation.
Tumor cells then release a variety of
growth factors that promote
bone resorption and increase the risk of skeletal complications.
Bisphosphonates are potent inhibitors of osteoclast activity that have demonstrated efficacy in the treatment of bone
metastases.
Bisphosphonates bind avidly to the bone matrix, are released during
bone resorption, and are subsequently internalized by osteoclasts, where they interfere with biochemical pathways and induce osteoclast apoptosis.
Bisphosphonates also antagonize osteoclastogenesis and promote the differentiation of osteoblasts. As a result,
bisphosphonates inhibit
tumor-induced
osteolysis and reduce skeletal morbidity. Furthermore, preclinical studies suggest that
bisphosphonates possess antitumor activity and can inhibit proliferation and induce apoptosis of tumor cell lines. In addition,
zoledronic acid, a new-generation
bisphosphonate, appears to inhibit
tumor cell invasion of the extracellular matrix. These data suggest that
zoledronic acid and other
bisphosphonates may play a role in the reduction of skeletal
tumor burden and the prevention of bone
metastasis.