Pathophysiology of Bone Metastases in Prostate Cancer Per-Anders Abrahamsson  European Urology Supplements  Volume 3, Issue 5, Pages 3-9 (November 2004) DOI: 10.1016/j.eursup.2004.09.001 Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 1 Pathophysiology of bone metastases. (A) In osteolytic bone disease, (1) metastatic tumor cells release humoral factors that stimulate osteoclastic recruitment and differentiation. (2) Osteoclasts begin to break down bone. (3) Bone resorption results in the release of growth factors that stimulate tumor-cell growth. (4) As the tumor proliferates, it produces substances that increase osteoclast-mediated bone resorption. (B) In osteoblastic bone disease, (1) metastatic tumor cells release growth factors that stimulate the activity of osteoclasts. (2) Tumor cells also secrete growth factors that stimulate the activity of osteoblasts. (3) Excessive new bone formation occurs around tumor-cell deposits. (4) Osteoclastic activity releases growth factors that stimulate tumor-cell growth. (5) Osteoblastic activation releases unidentified osteoblastic growth factors that also stimulate tumor-cell growth. PTHrP = Parathyroid hormone-related protein; IL-6 = Interleukin-6; TGF-β = Transforming growth factor-beta; BMP = Bone morphogenetic protein; IGF = Insulin-like growth factor; FGF = Fibroblast growth factor. Adapted from European Urology, Vol. 45, Saad F, Schulman CC, Role of bisphosphonates in prostate cancer, pages 26–34, copyright 2004, with permission from the European Association of Urology [29]. European Urology Supplements 2004 3, 3-9DOI: (10.1016/j.eursup.2004.09.001) Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 2 Bone marker levels in patients with bone metastases were significantly higher in osteoblastic disease than in either osteolytic or mixed disease. (A) Urinary levels of N-telopeptide, a marker of bone resorption, and (B) serum levels of bone-specific alkaline phosphatase, a marker of bone formation, in 77 patients with osteoblastic, osteolytic, or mixed bone lesions. BCE = Bone collagen equivalents; Cr = Creatinine. Adapted from Demers et al., Cancer, Vol. 88, No. 12 (suppl), 2000, pages 2919–2926. Copyright © 2000 American Cancer Society. Reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc. [44]. European Urology Supplements 2004 3, 3-9DOI: (10.1016/j.eursup.2004.09.001) Copyright © 2004 Elsevier B.V. Terms and Conditions

Fig. 3 Bone marker levels in patients with bone metastases were higher in patients with prostate cancer than in patients with either breast cancer or gastrointestinal (GI) cancer. (A) Urinary levels of N-telopeptide, and (B) serum levels of bone-specific alkaline phosphatase, in 97 patients with breast, prostate, or GI cancer with bone metastases. BCE = Bone collagen equivalents; Cr = Creatinine. Adapted with permission from Demers LM, Costa L, Lipton A, Biochemical markers and skeletal metastases, Clinical Orthopaedics and Related Research, Vol. 415, special issue, pages S138–S147 [45]. European Urology Supplements 2004 3, 3-9DOI: (10.1016/j.eursup.2004.09.001) Copyright © 2004 Elsevier B.V. Terms and Conditions