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13 - The place of bisphosphonates in the management of breast cancer
- Edited by Zenon Rayter, Bristol Royal Infirmary, Janine Mansi, St George's Hospital Medical School, University of London
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- Book:
- Medical Therapy of Breast Cancer
- Published online:
- 06 January 2010
- Print publication:
- 09 January 2003, pp 340-356
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- Chapter
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Summary
Introduction
Bone pain, fractures and hypercalcaemia are important causes of morbidity in patients with metastatic breast cancer despite recent advances in endocrine and cytotoxic therapy. These skeletal complications arise because of progressive focal or generalized osteolysis. Osteolysis occurs because of osteoclast activation, either directly by tumour products or by products secreted by nearby host cells in response to tumour cell products (Mundy et al., 1984). Since the osteoclast plays a central role in focal or generalized osteolysis, inhibitors of osteoclast function may lead to palliation and, in some cases, to prevention of osteolytic destruction and its complications (Taube et al., 1994). It is also possible that the growth and development of bone metastases may be inhibited in a proportion of patients and the bone loss associated with premature menopause induced by adjuvant chemotherapy may be prevented.
The clinical problem
Skeletal pain, fracture and hypercalcaemia are well recognized by oncologists as major causes of morbidity in patients with breast cancer. Vertebral fractures not only cause pain and disability, but may lead to spinal cord compression. In women, the problems of bone metastases are compounded by the propensity to osteoporosis. Women have a lower total bone mass than men and the threshold for developing fractures tends to be reached at an earlier age than in men. In addition, in premenopausal women with breast cancer, the increasing use of adjuvant cytotoxic chemotherapy or adjuvant LHRH analogues leads to earlier menopause with subsequent earlier accelerated loss of bone.
Normal and abnormal bone remodeling
Bone remodelling is a dynamic process occurring in response to poorly understood physical and chemical forces along lines of stress (Kaplan, 1987).