Bone Metastases: An Overview

Filipa Macedo, Katia Ladeira, Filipa Pinho, Nadine Saraiva, Nuno Bonito, Luisa Pinto, Francisco Goncalves, Filipa Macedo, Katia Ladeira, Filipa Pinho, Nadine Saraiva, Nuno Bonito, Luisa Pinto, Francisco Goncalves

Abstract

Bone is a frequent site of metastases and typically indicates a short-term prognosis in cancer patients. Once cancer has spread to the bones it can rarely be cured, but often it can still be treated to slow its growth. The majority of skeletal metastases are due to breast and prostate cancer. Bone metastasis is actually much more common than primary bone cancers, especially in adults. The diagnosis is based on signs, symptoms and imaging. New classes of drugs and new interventions are given a better quality of life to these patients and improved the expectancy of life. It is necessary a multidisciplinary approach to treat patients with bone metastasis. In this paper we review the types, clinical approach and treatment of bone metastases.

Keywords: Bone metastasis; bisphosphonates; denosumab; fractures; radiotherapy.

References

    1. Chambers A, Naumov G, Varghese H, et al. Critical steps in hematogenous metastasis: an overview. Surg Oncol Clin N Am 2001;10:243-55.
    1. Luzzi KJ, MacDonald IC, Schmidt EE, et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 1998;153:865-73.
    1. Coleman R. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 2001;27:165-76.
    1. Cecchini M, Wetterwald A, Pluijm G, Thalmann G. Molecular and biological mechanisms of bone metastasis. EAU Update Series 2005;3:214-26.
    1. Selvaggi G, Scagliotti G. Management of bone metastases in cancer: a review. Clin Rev Oncol Hematol 2005;56:365-78.
    1. Taube T, Elomaa I, Blomqvist C. Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer. Bone 1994;15:161.
    1. Southby J, Kissin M, Danks J, et al. Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. Cancer Res 1990;50:7710-6.
    1. Kohno N, Kitazawa S, Fukase M, et al. The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases. Surg Today 1994;24:215-20.
    1. Dougall W, Glaccum M, Charrier K, et al. Rank is essential for osteoclast and lymph node development. Genes Dev 1999;13:2412-24.
    1. Keller E, Zhang J, Cooper C, et al. Prostate carcinoma skeletal metastases: cross-talk between tumor and bone. Cancer Metastasis Rev 2001;20:333-49.
    1. Iwamura M, Hellman J, Cockett A, et al. Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen. Urology 1996;48:317-25.
    1. Yang X, Karsenty G. Transcription factors in bone: developmental and pathological aspects. Trends Mol Med 2002;8:340-5.
    1. Coleman R, Seaman J. The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastasis. Semin Oncol 2001;28:11-6.
    1. Berrettoni B.A, Carter JR. Mechanisms of cancer metastasis to bone. J Bone Joint Surg Am 1986;68:308-12.
    1. Franks LM. The spread of prostatic carcinoma to the bones. J Pathol Bacteriol 1953;66:91-3.
    1. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994;76:301-14.
    1. Mazo IB, von Andrian UH. Adhesion and homing of blood-borne cells in bone marrow microvessels. J Leukoc Biol 1999;66:25-32.
    1. Sipkins DA, Wei X, Wu JW, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature 2005;435:969-73.
    1. Balkwill F. Cancer and the chemokine network. Nat Rev Cancer 2004;4:540-50.
    1. Guo W, Giancotti FG. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol 2004;5:816-26.
    1. Russel H, Hicks J, Okcu M, Nuchtern J. CXCR4 expression in neuroblastoma primary tumors is associated with clinical presentation of bone and bone marrow metastases. J Pediatr Surg 2004;39:1506-11.
    1. Jones D, Nakashima T, Sanchez O, et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature 2006;440:692-6.
    1. Papotti M, Kalebic T, Volante M, et al. Bone sialoprotein is predictive of bone metastases in resectable non-small-cell lung cancer: a retrospective case-control study. J Clin Oncol 2006;24:4818-24.
    1. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889;1:571-3.
    1. Coleman R, Rubens R. The clinical course of bone metastases from breast cancer. Br J Cancer 1987;55:61-6.
    1. Coleman R, Smith P, Rubens R. Clinical course and prognostic factors following recurrence from breast cancer. Br J Cancer 1998;17:336-40.
    1. Robson M, Dawson N. How is androgen dependent metastatic prostate cancer best treated? Haematol Oncol Clinics North Am 1996;10:727-47.
    1. Maisano R, Pergolizzi S, Cascinu S. Novel therapeutic approaches to cancer patients with bone metastasis. Crit Rev Oncol Hematol 2001;40:239-50.
    1. Higinbotham N, Marcove R. The management of pathological fractures. J Trauma 1965;5:792-9.
    1. Nielson O, Munro A, Tannock I. Bone metastases: pathophysiology and management policy. J Clin Oncol 1991;9:509-24.
    1. Hadji P, Aapro M, Body J, et al. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol 2011;22:2546-55.
    1. Clohisy D, Mantyh P. Bone cancer pain. Cancer 2003;97:866.
    1. Coleman R, Body J, Aapro M, et al. Bone health in cancer patients: ESMO clinical practice guidelines. Ann Oncol 2014;25:124-37.
    1. Algra P, Bloem J, Tissing H, et al. Detection of vertebral metastases: comparison between MRI and bone scintigraphy. Radiographics 1991;11:219-32.
    1. Vinholes J, Coleman R, Eastell R. Effects of bone metastases on bone metabolism: implications for diagnosis, imaging and assessment of response to cancer treatment. Cancer Treat Rev 1996;22:289-31.
    1. Rosenthal D. Radiologic diagnosis of bone metastases. Cancer 1997;80:1595-607.
    1. Evans A, Robertson J. Magnetic resonance imaging versus radionuclide scintigraphy for screening in bone metastases. Clin Radiol 2000;55:653.
    1. Marom E, McAdams H, Erasmus J, et al. Staging non-small cell lung cancer with whole-body PET. Radiology 1999;212:803-9.
    1. Yang S, Liang J, Lin F, et al. Comparing whole-body 18FDG PET and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer. J Cancer Res Clin Oncol 2002;128:325-8.
    1. Schirrmeister H, Guhlmann A, Eisner K, et al. Sensitivity in detecting osseous lesions depends on anatomic localization: planar bone scintigraphy versus 18F PET. J Nucl Med 1999;40:1623-9.
    1. Shreve P, Grossman H, Gross M, Wahl R. Metastatic prostate cancer: initial findings of PET with 2-deoxy-2 (F-18) fluoro-d-glucose. Radiology 1996;199:751-5.
    1. Rogers M, Xiong X, Ji X, et al. Inhibition of growth of dictyostelium discoideum amoebae by bisphosphonates is dependent on cellular uptake. Pharmacol Res 1997;14:625-30.
    1. Rogers M, Watts D, Russel R. Overview of bisphosphonates. Cancer 1997;80:1652-60.
    1. Body J, Coleman R, Piccart M. Use of bisphosphonates in cancer patients. Cancer Treat Rev 1996;22:265-87.
    1. Vinholes J, Purohit O, Abbey M, et al. Relationships between biochemical and symptomatic response in double-blind trial of pamidronate for metastatic bone disease. Ann Oncol 1997;8:1243-50.
    1. Green JR, Rogers MJ. Pharmacologic profile of zoledronic acid: a highly potent inhibitor of bone resorption. Drug Dev Res 2002;55:210-24.
    1. Wellington K, Goa KL. Zoledronic acid. A review of its use in the management of bone metastases and hypercalcemia of malignancy. Drugs 2003;63:417-37.
    1. Guenther A, Gordon S, Tiemann M, et al. The bisphosphonate zoledronic acid has antimyeloma activity in vivo by inhibition of protein prenylation. Int J Cancer 2010;126:239-46.
    1. Rennert G, Pinchev M, Rennert H, Gruber S. Use of bisphosphonates and reduced risk of colorectal cancer. J Clin Oncol 2011;29:1146-50.
    1. Rennert G, Pinchev M, Rennert HS. Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 2010;28:3577-81.
    1. Chlebowski R, Chen Z, Cauley J, et al. Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 2010;28:3582-90.
    1. Dedes P, Gialeli C, Tsonis A, et al. Expression of matrix macromolecules and functional properties of breast cancer cells are modulated by the bisphosphonate zoledronic acid. Biochim Biophys Acta 2012;1820:1926-39.
    1. Iguchi K. Effect of bisphosphonates on anticancer activity in prostate cancer cells. Yakugaku Zasshi 2012;132:1025-30.
    1. Aapro M, Saad F. Bone-modifying agents in the treatment of bone metastases in patients with advanced genitourinary malignancies: a focus on zoledronic acid. Ther Adv Urol 2012;4:85-101.
    1. Mhaskar R, Redzepovic J, Wheatley K, et al. Bisphosphonates in multiple myeloma. Cochrane Database Syst Rev 2010;17:CD003188.
    1. Huang W, Huang C, Lui J, et al. Zoledronic acid as an adjuvant therapy in patients with breast cancer: a systematic review and meta-analysis. PLoS One 2012;7:e40783.
    1. Steger G, Bartsch R. Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion. Ther Adv Med Oncol 2011;3:233-43.
    1. Yee A, Raje N. Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients. Clin Interv Aging 2012;7:331-8.
    1. Migliorati C, Epstein J, Abt E, Berenson J. Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review. Nat Rev Endocrinol 2011;7:34-42.
    1. Baron R, Ferrari S, Russell R. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 2011;48:677-92.
    1. Stopeck A, Lipton A, Body J, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 2010;28:5132-9.
    1. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-22.
    1. Anastasilakis A, Toulis K, Goulis D, et al. Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis. Horm Metab Res 2009;41:721-9.
    1. Henry D, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011;29:1125-32.
    1. Janjan N. Radiation of bone metastases: conventional techniques and the role of systemic radiopharmaceuticals. Cancer 1997;80:1628-45.
    1. Tong C, Gillick L, Hendrickson F. The palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group. Cancer 1982;50:893-9.
    1. Salazar O, Rubin P, Hendrickson F, et al. Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors: final Radiation Therapy Oncology Group report. Cancer 1986;58:29-36.
    1. Poulter C, Cosmatos D, Rubin P, et al. A report of RTOG 8206: a phase III study of whether the addition of single dose hemi-body irradiation to standard fractionated local field irradiation is more effective than local field irradiation alone in the treatment of symptomatic osseous metastases. Int J Radiat Oncol Biol Phys 1992;23:207-14.
    1. Robinson R, Preston D, Baxter K, et al. Clinical experience with strontium89 in prostatic and breast cancer patients. Semin Oncol 1993;20:44-8.
    1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter Radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;18:213-23.
    1. American Cancer Society. Bone metastasis. Available from:
    1. Saliken J, McKinnon J, Gray R. CT for monitoring cryotherapy. AJR Am J Roentgenol 1996;166:853-5.
    1. Thacker P, Callstrom M, Curry T, et al. Palliation of painful metastatic disease involving bone with image-guided treatment: comparison of patients immediate response to radiofrequency ablation and cryoablation. AJR Am J Roentgenol 2011;197:510-5.
    1. Callstrom M, Dupuy D, Solomon S, et al. Percutaneous image-guided cryoablation of painful metastases involving bone: multicenter trial. Cancer 2013;119:1033-41.
    1. Lee R, Saylor P, Michaelson M, et al. A dose-ranging study of cabozantinib in men with castration-resistant prostate cancer and bone metastases. Clin Cancer Res 2013;19:3088-94.
    1. Jhaveri P, Teh B, Bloch C, et al. Stereotactic body radiotherapy in the management of painful bone metastases. Oncology 2008;22:782-8.
    1. Sohn S, Chung C. The role of stereotactic radiosurgery in metastasis to the spine. J Korean Neurosurg Soc 2012;51:1-7.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe