TY - JOUR
T1 - Biology of bone metastases
T2 - Causes and consequences
AU - Harvey, Harold A.
AU - Von Reyn Cream, Leah
N1 - Funding Information:
Dr Harvey has received research support from Pfizer, Novartis Oncology, AstraZeneca, Aventis, and Wyeth. He has also served as a paid consultant or been on the Advisory Board of Quintiles and GlaxoSmithKline and has been a member of the Speaker's Bureau for Lilly Oncology, Genentech BioOncology, and Novartis Oncology. Dr von Reyn Cream has no relevant relationships to disclose. This article includes discussion of investigational and/or unlabeled use of drugs, including the use of denosumab in patients with bone metastases; zoledronic acid, clodronate, and ibandronate in patients with early-stage breast cancer; and zoledronic acid in patients with prostate cancer but without any established bone metastases.
PY - 2007/7
Y1 - 2007/7
N2 - Breast cancer is a highly osteotropic neoplasm, and as many as 75% of patients with metastatic disease will have involvement of the bony skeleton. On radiologic examination, these metastases are predominantly osteolytic but can be osteoblastic or mixed. The mechanisms by which metastases are formed are complex, involving many steps that include angiogenesis, invasion, and proliferation in the bone microenvironment. Tumor cells in the bone microenvironment produce a large number of cytokines that stimulate osteoclastic activity. Increased osteoclastic activity, in turn, leads to production of a variety of lymphokines and growth factors that can increase tumor cell proliferation. Thus, a cytokine network is established, which results in an imbalance of the processes of bone formation and bone resorption. As tumor burden in bone increases, osteoclast-mediated bone resorption is accelerated, resulting in loss of bone strength, fractures, pain, and other morbidities. Tumor cells metastatic to bone can also secrete growth factors, leading to increased osteoblastic activity. Osteoblasts lay down an excess of new bone that is structurally weak. There is considerable crosstalk between osteoclasts, osteoblasts, macrophages, and other cellular elements within the bone environment. The increasing understanding of the biology of bone metastases has opened the door to improved management of this important clinical problem. Current treatment strategies include approaches to reduce tumor burden and developing treatments that directly inhibit osteoclast function. The bisphosphonates are a class of drugs that inhibit osteoclast recruitment and function. Several highly potent bisphosphonates are now available for clinical use and represent an important adjunct in the management of bone metastases from breast cancer, multiple myeloma, and several other types of malignancies. Some newer therapeutic approaches include agents designed to inhibit the osteoclast-osteoblast signaling interactions or alter processes of adhesion and invasion.
AB - Breast cancer is a highly osteotropic neoplasm, and as many as 75% of patients with metastatic disease will have involvement of the bony skeleton. On radiologic examination, these metastases are predominantly osteolytic but can be osteoblastic or mixed. The mechanisms by which metastases are formed are complex, involving many steps that include angiogenesis, invasion, and proliferation in the bone microenvironment. Tumor cells in the bone microenvironment produce a large number of cytokines that stimulate osteoclastic activity. Increased osteoclastic activity, in turn, leads to production of a variety of lymphokines and growth factors that can increase tumor cell proliferation. Thus, a cytokine network is established, which results in an imbalance of the processes of bone formation and bone resorption. As tumor burden in bone increases, osteoclast-mediated bone resorption is accelerated, resulting in loss of bone strength, fractures, pain, and other morbidities. Tumor cells metastatic to bone can also secrete growth factors, leading to increased osteoblastic activity. Osteoblasts lay down an excess of new bone that is structurally weak. There is considerable crosstalk between osteoclasts, osteoblasts, macrophages, and other cellular elements within the bone environment. The increasing understanding of the biology of bone metastases has opened the door to improved management of this important clinical problem. Current treatment strategies include approaches to reduce tumor burden and developing treatments that directly inhibit osteoclast function. The bisphosphonates are a class of drugs that inhibit osteoclast recruitment and function. Several highly potent bisphosphonates are now available for clinical use and represent an important adjunct in the management of bone metastases from breast cancer, multiple myeloma, and several other types of malignancies. Some newer therapeutic approaches include agents designed to inhibit the osteoclast-osteoblast signaling interactions or alter processes of adhesion and invasion.
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U2 - 10.3816/CBC.2007.s.001
DO - 10.3816/CBC.2007.s.001
M3 - Article
C2 - 17683652
AN - SCOPUS:34548262727
SN - 1526-8209
VL - 7
SP - S7-S13
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
IS - SUPPL. 1
ER -