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Richard L. Theriault

Breast cancer frequently metastasizes to bone. Metastases result in skeletal morbidity including pathologic fractures, the need for radiation or surgery to bone, spinal cord compression and hypercalcemia. The pathophysiology of bone destruction is related to activation of osteoclasts by tumor-derived and bone marrow microenvironmental factors. One prominent osteoclast–activating factor associated with breast cancer is parathyroid hormone-related peptide (PTHrP). Bisphosphonates have been shown to impair osteoclast activity by decreasing recruitment from the monocyte macrophage cell line, inhibiting osteoclast function at the bone site and causing osteoclasts to undergo apoptosis. Clinical studies with bisphosphonates show an improvement in the control of hypercalcemia and a reduction in skeletal related morbidity with administration of pamidronate and zoledronic acid. Bisphosphonates have become the standard of care for osteolytic metastases associated with breast cancer. Recent data with zoledronic acid found that skeletal related morbidity may be reduced regardless of the radiographic picture of skeletal metastases. Thus, zoledronic acid may be valuable in osteolytic and osteoblastic disease as well as in disease with an osteolytic or osteoblastic radiographic appearance. In breast cancer with osteolytic disease, zoledronic acid may be more effective than pamidronate in reducing skeletal morbidity and prolonging the time to first skeletal event.

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Noopur S. Raje, Andrew J. Yee and G. David Roodman

mineral phase of bone. They reduce osteoclast activity through inhibiting farnesyl pyrophosphate synthase. 16 Bisphosphonates have a well-established role in the treatment of osteoporosis 17 , 18 and metastatic bone involvement from solid tumors. 19 - 21

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Emma Gargus, Rebecca Deans, Antoinette Anazodo and Teresa K. Woodruff

, resulting in more bone resorption than formation. There is a net bone loss of 2% to 3% per year after menopause. Bone remodeling is reversible in the short-term, but with time, high osteoclast activity can result in permanent loss of bony microarchitecture

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Julie R. Gralow, J. Sybil Biermann, Azeez Farooki, Monica N. Fornier, Robert F. Gagel, Rashmi Kumar, Georgia Litsas, Rana McKay, Donald A. Podoloff, Sandy Srinivas and Catherine H. Van Poznak

survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity . J Thorac Oncol 2008 ; 3 : 228 – 236 . 257 Lipton A Theriault RL Hortobagyi GN . Pamidronate prevents skeletal complications and

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Robert W. Carlson, D. Craig Allred, Benjamin O. Anderson, Harold J. Burstein, W. Bradford Carter, Stephen B. Edge, John K. Erban, William B. Farrar, Andres Forero, Sharon Hermes Giordano, Lori J. Goldstein, William J. Gradishar, Daniel F. Hayes, Clifford A. Hudis, Britt-Marie Ljung, David A. Mankoff, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Lori J. Pierce, Elizabeth C. Reed, Jasgit Sachdev, Mary Lou Smith, George Somlo, John H. Ward, Antonio C. Wolff and Richard Zellars

section). These 2 patient subsets are then stratified further according to tumor hormone receptor and HER2 status (see page 154). Supportive Therapy for Bone Metastasis: Treatment targeting osteoclast activity is of value in patients with metastatic