Their effects are unclear, and long term trials are needed

Bisphosphonates are potent inhibitors of the osteoclastic bone resorption that is associated with skeletal metastases, with proved efficacy in reducing skeletal complications in metastatic cancer. Randomised clinical trials investigating the adjuvant use of bisphosphonates to prevent bone metastases in patients with breast cancer have yielded intriguing yet conflicting results. Defining the potential role of these agents in the treatment of breast cancer is of great clinical relevance.

The skeleton is the first site of recurrence in 25-40% of patients with metastatic breast cancer. The development of bone metastases entails complex interactions between cancer cells and the microenvironment of bones. In the early establishment of metastases, bone is destroyed by the osteoclast, which is activated by a variety of cytokines produced directly or indirectly by the tumour cell. As bone matrix is broken down, a rich supply of mitogenic factors is released, which in turn can lead to increased proliferation of cancer cells.

Bisphosphonates are effective in treating conditions in which excessive bone resorption and osteoclast activity prevail, including osteoporosis and Paget's disease of bone. Several randomised clinical trials in patients with breast cancer with bone metastases have shown the ability of bisphosphonates to reduce skeletal related events and symptoms, including pathological fractures, surgery, radiation, compression of the spinal cord, hypercalcaemia, and pain, although they …