New results from the use of bisphosphonates in cancer patients.
OBJECTIVE
Metastatic bone disease results from cancer-bone cell interactions in the bone marrow microenvironment rather than direct destruction by cancer cells. Additionally, cancer treatments may have adverse effects on bone health. Therefore, a clear rationale exists for bone-targeted therapies to prevent skeletal complications and potentially modify the underlying disease.


RESULTS
Studies in metastatic disease have focused on refining treatment, largely through the use of bone metabolism markers. Use of bisphosphonates in early cancer has become increasingly important to prevent bone loss. Recent results, notably with zoledronic acid, indicate that bone mineral density can be maintained and increased bone turnover normalized. Bisphosphonates are potent inhibitors of bone osteolysis and may impede both the development of bone metastases and survival of dormant cells in the marrow microenvironment. Additionally, bisphosphonates may have direct effects on tumour cells, especially in combination with chemotherapy. Clinical trial results in breast cancer with clodronate were inconclusive, but recent data with zoledronic acid suggest that bisphosphonates may indeed modify the course of the disease.


CONCLUSIONS
The roles of bisphosphonates in metastatic bone disease and the prevention of cancer treatment induced bone loss have been defined. However, results from ongoing metastasis prevention trials are required before routine adjuvant bisphosphonates can be recommended.
Coleman
Robert
R
Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, WhithamRoad, Sheffield S103LZ, UK. r.e.coleman@sheffield.ac.uk
Gnant
Michael
M
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary; D001862:Bone Resorption / Q000139:chemically induced* / Q000188:drug therapy / Q000517:prevention & control; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates