Bone-targeted treatments with
bisphosphonates and
denosumab, which reduce
bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant
bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of
growth factor and
cytokine signaling between
tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the
cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III)
breast cancer, treatment with the
bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with
goserelin, which suppresses ovarian function by inhibiting the production of ovarian
hormones. Additionally, in castrate-resistant
prostate cancer, treatment with
denosumab delays the development of bone
metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive
hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic)
cancers, survival benefits have been observed in patients with
multiple myeloma and in patients with other solid
tumors with rapid rates of bone destruction who received treatment with
zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.