Bisphosphonates are the standard therapy for osteoporosis. The primary example is alendronate (Fosamax), but also include clodronate (Bonefos), pamidronate (Aredia), zoledronic acid (Reclast), and ibandronate (Boniva). The drugs aid in reducing bone loss by inhibiting the formation of osteoclast cells from immature cells, or by stimulating apooptosis (cell death) in mature osteoclasts. Osteoclast are responsible for resorption (breakdown) of bone.
Bisphosphonates Decrease Bone Disorders Due to Breast Cancer Metastases
Breast cancer cells that have metastasized have a marked affinity for bone tissue. The cancer cells promote resorption of bone causing the release of growth factors and cytokines. These biological compounds result in an increased attraction and growth of cancer cells to bone. The primary resultant metabolic disorder is hypercalcemia, or excess calcium in the blood. As the disease progresses, pathological fractures and spinal cord compression may result.
Bisphosphonate treatment interferes with this adhesion of cancer cells to bone. ( Brown) Clodronate (given orally) and pamidronate (given intravenously) have been used clinically, but a considerable amount of research has been conducted on the use of zoledronic acid, which may be more potent, and is easier to administer.
Bisphosphonates Treat Cancer Apart from its Effects on Bone
Matrix metalloproteinase (MMP) enzymes digest tissue proteins such as basement membranes that are located between epithelial linings of tissues. Although MMP enzymes are active in normal body processes, cancer cells recruit stromal cells to secrete excess MMP. The breakdown of basement membranes permits cancer cells to invade adjacent tissues.
Recent studies have shown that bisposphonates inhibit the proteolytic activity of MMPs. Several studies found that the use of zoledronic acid in conjunction with chemotherapy had a synergistic effect (the combination had a greater effect than chemotherapy alone). A Korean study showed that zoledronic acid in combination with either chemotherapy or hormonal therapy improved survival time in hormone receptor-negative breast cancer patients.
Bisphosphonates May Prevent Metastatic Breast Cancer
Two long-term studies on women taking bisphosphonates for osterporosis were also evaluated for incidence of breast cancer. (Chustecka) The very large Women's Health Initiative study showed that the use of bisphosphonates resulted in a 34% reduction in invasive breast cancer. A smaller Israeli study found that the long-term use of bisphosphonates also resulted in a 34% reduction in breast cancer.
Bisphosphonates: An Important Adjunct for Breast Cancer Therapy
Bisphosphonates in combination with chemotherapy, radiation, or hormone therapy have been shown to reduce metastatic spread of breast cancer, to decrease bone complications, and to help prevent breast cancer.
Sources:
Brown J. and Coleman R. The Present and Future Role of Bisphosphonates in the Management of Patients With Breast Cancer. Breast Cancer Research. 2002;4:24-29.
Chustecka Z. Oral Bisphosphonates May Prevent Invasive Breast Cancer. Medscape.com. 2009 Dec 11.
Park H. et al. Potential Antitumor Effects of Nitrogen-Containing Bisphosphonate in Hormone Receptor Negative Breast Cancer Patients With Bone Metastasis. BMC Cancer. 2009;9:154-162.
Senaratne S. et al. The Role of Bisphonates in Breast Cancer: Direct Effects of Bisphosphonates on Breast Cancer Cells. Breast Cancer Research. 2002; 4: 18-23.
David Olle - I have been a freelance writer since 1995, specializing in medicine, science, and nutrition topics. I have been involved in the following ...
