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Bone Metabolism in Cancer

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Central Nervous System Metastases

Abstract

Bone metastases require a multidisciplinary treatment approach to provide optimal care for affected patients. Once metastasized to bone, cancer cells disturb the balance of bone formation and resorption, resulting in either predominantly osteolytic or sclerotic bone lesions. While the complex underlying pathophysiology of bone and cancer interactions is increasingly understood, pharmacological treatment approaches are currently limited to antiresorptive strategies. Antiresorptive treatment with bisphosphonates or the receptor activator of nuclear factor kappa-Β ligand (RANKL) antibody denosumab has proven efficacy in reducing skeletal-related events and positively affecting the patients’ quality of life. The following chapter gives a concise overview of the underlying pathophysiology of bone metastases and data on pharmacological treatment options.

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References

  1. Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep. 2014;3:1–10.

    CAS  Google Scholar 

  2. Walsh JS. Normal bone physiology, remodelling and its hormonal regulation. Surgery. 2014;33:1–6.

    Google Scholar 

  3. Crockett JC, Rogers MJ, Coxon FP, Hocking LJ, Helfrich MH. Bone remodelling at a glance. J Cell Sci. 2011;124:991–8.

    Article  CAS  PubMed  Google Scholar 

  4. Almeida M, Laurent MR, Dubois V, Claessens F, Brien CAO, Bouillon R, et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol Rev. 2017;97:135–87.

    Article  PubMed  Google Scholar 

  5. Rachner TD, Khosla S, Hofb LC. Osteoporosis: now and the future. Lancet. 2011;377:1276–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lips P, Van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011;25:585–91.

    Article  CAS  PubMed  Google Scholar 

  7. Bassett JHD, Williams GR. Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev. 2016;37:135–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schett G. Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur J Clin Investig. 2011;41:1361–6.

    Article  CAS  Google Scholar 

  9. Smolen JS, Redlich K, Zwerina J, Aletaha D, Steiner G, Schett G. Pro-inflammatory cytokines in rheumatoid arthritis pathogenetic and therapeutic aspects. Clin Rev Allergy Immunol. 2005;28:239–48.

    Article  CAS  PubMed  Google Scholar 

  10. Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2:584–93.

    Article  CAS  PubMed  Google Scholar 

  11. Paget S. The distribution of secondary growths in cancer of the breast. Lancet. 1889;133:571–3.

    Article  Google Scholar 

  12. Hofbauer LC, Rachner T, Singh SK. Fatal attraction: why breast cancer cells home to bone. Breast Cancer Res. 2008;10:101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655–64.

    Article  CAS  PubMed  Google Scholar 

  14. Guise TA, Mohammad KS, Clines G, Stebbins EG, Wong DH, Higgins LS, et al. Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res. 2006;12:6213–7.

    Article  Google Scholar 

  15. Weilbaecher KN, Guise TA, LK MC. Cancer to bone: a fatal attraction. Nat Rev Cancer. 2011;11:411–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rachner TD, Göbel A, Benad-Mehner P, Hofbauer LC, Rauner M. Dickkopf-1 as a mediator and novel target in malignant bone disease. Cancer Lett. 2014;346:172–7.

    Article  CAS  PubMed  Google Scholar 

  17. Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015;143:471–8.

    Article  PubMed  Google Scholar 

  18. Hernandez RK, Wade SW, Reich A, Pirolli M, Liede A, Lyman GH. Incidence of bone metastases in patients with solid tumors: analysis of oncology electronic medical records in the United States. BMC Cancer. 2018;18:1–11.

    Article  Google Scholar 

  19. Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13(4):581–9.

    Article  CAS  PubMed  Google Scholar 

  20. Polascik T, Mouraviev V. Zoledronic acid in the management of metastatic bone disease. Ther Clin Risk Manag. 2008;4:261–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Petrut B, Simmons C, Broom R, Trinkaus M. Pharmacotherapy of bone metastases in in breast cancer patients. Expert Opin Pharmacother. 2008;6566:937–45.

    Article  CAS  Google Scholar 

  22. Ross JR, Saunders Y, Edmonds PM, Patel S, Broadley KE, Johnston SRD. Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer. BMJ. 2003;327:1–6.

    Article  Google Scholar 

  23. Jagdev S, Purohit P, Herling C, Coleman R. Comparison of the effects of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease. Ann Oncol. 2001;12:1433–8.

    Article  CAS  PubMed  Google Scholar 

  24. Rosen LS, Gordon DH, Dugan W, Major P, Eisenberg PD, Provencher L, et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer. 2003;100:36–43.

    Article  CAS  Google Scholar 

  25. Pavlakis N, Rl S. Bisphosphonates for breast cancer (review). Cochrane Database Syst Rev. 2005;3:1–49.

    Google Scholar 

  26. O’Carrigan B, Wong M, Willson M, Stockler M, Pavlakis N, Goodwin A. Bisphosphonates and other bone agents for breast cancer (review). Cochrane Database Syst Rev. 2017;10:CD003474.

    Google Scholar 

  27. Hadji P, Aapro MS, Body J, Gnant M, Luisa M, Yves J, et al. Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG. J Bone Oncol. 2017;7:1–12.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rachner T, Coleman R, Hadji P, Hofbauer L. Bone health during endocrine therapy for cancer. Lancet Diabetes Endocrinol. 2018;6(11):901–10.

    Article  CAS  Google Scholar 

  29. Early Breast Cancer Trialists’ Collaborative Group E. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015;386:1353–61.

    Article  CAS  Google Scholar 

  30. Saad F, Gleason DM, Murray R, Venner P, Lacombe L, Chin JL, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone- refractory prostate cancer for the zoledronic acid prostate cancer study group. J Natl Cancer Inst. 2004;96:879–82.

    Article  CAS  PubMed  Google Scholar 

  31. Hoskin P, Sundar S, Reczko K, Forsyth S, Mithal N, Sizer B, et al. A multicenter randomized trial of ibandronate compared with single-dose radiotherapy for localized metastatic bone pain in prostate cancer. J Natl Cancer Inst. 2015;107:1–9.

    Article  CAS  Google Scholar 

  32. van Driel M, van Leeuwen JPTM. Cancer and bone: a complex complex. Arch Biochem Biophys. 2014;561:159–66.

    Article  PubMed  CAS  Google Scholar 

  33. Lahtinen R, Laakso M, Palva I, Virkkunen P, Elomaa I. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Lancet. 1992;340:1049–52.

    Article  CAS  PubMed  Google Scholar 

  34. McCloskey E, MacLennan I, Drayson M, Chapman C, Dunn J, Kanis J. A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. Br J Haematol. 1998;100:317–25.

    Article  CAS  PubMed  Google Scholar 

  35. McCloskey EV, Dunn JA, Kanis JA, MacLennan ICM, Drayson MT. Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma. Br J Haematol. 2001;113:1035–43.

    Article  CAS  PubMed  Google Scholar 

  36. Brincker H, Westin J, Abildgaard N, Gimsing P, Turesson I, Hedenus M, et al. Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Br J Haematol. 1998;101:280–6.

    Article  CAS  PubMed  Google Scholar 

  37. Berenson J, Lichtenstein A, Porter L, Dimopoulos M, Bordoni R, George S, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N Engl J Med. 1996;334:488–93.

    Article  CAS  PubMed  Google Scholar 

  38. Rosen L, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J. 2001;7:377–87.

    CAS  PubMed  Google Scholar 

  39. Morgan GJ, Child JA, Gregory WM, Szubert AJ, Cocks K, Bell SE, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12:743–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mhaskar R, Redzepovic J, Wheatley K, Oac C, Miladinovic B, Glasmacher A, et al. Bisphosphonates in multiple myeloma: a network meta- analysis (review). Cochrane Database Syst Rev. 2012;5:1–99.

    Google Scholar 

  41. Terpos E, Morgan G, Dimopoulos MA, Drake MT, Lentzsch S, Shimizu K, et al. International myeloma working group recommendations for the treatment of multiple myeloma – related bone disease. J Clin Oncol. 2013;31:2347–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood. 2000;96:384–92.

    Article  CAS  PubMed  Google Scholar 

  43. Reyes C, Hitz M, Prieto-alhambra D, Abrahamsen B. Risks and benefits of bisphosphonate therapies. J Cell Mol Med. 2016;28:20–8.

    Google Scholar 

  44. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stopeck AT, Lipton A, Body J-J, Steger GG, Tonkin K, de Boer RH, 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.

    Article  CAS  PubMed  Google Scholar 

  46. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, 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.

    Article  CAS  PubMed  Google Scholar 

  47. Raje N, Terpos E, Willenbacher W, Shimizu K, García-sanz R, Durie B, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19:370–81.

    Article  CAS  PubMed  Google Scholar 

  48. Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379:39–46.

    Article  CAS  PubMed  Google Scholar 

  49. Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;6736:1–11.

    Google Scholar 

  50. Coleman R, Finkelstein D, Barrios C, Martin M, Iwata H, Glaspy J, et al. Adjuvant denosumab in early breast cancer: first results from the international multicenter randomized phase III placebo controlled D-CARE study. J Clin Oncol. 2018;36:(suppl; abstr 501).

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine III, Division for Endocrinology, Diabetes and Bone Disorders, University Hospital “Carl Gustav Carus”, Dresden, Germany

    Tilman D. Rachner, Lorenz C. Hofbauer & Andy Göbel

Authors
  1. Tilman D. Rachner
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  2. Lorenz C. Hofbauer
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  3. Andy Göbel
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Corresponding author

Correspondence to Tilman D. Rachner .

Editor information

Editors and Affiliations

  1. Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medicine, Director - Brain Metastases Program, New York, NY, USA

    Rohan Ramakrishna

  2. Department of Neurology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA

    Rajiv S. Magge

  3. Department of Neurological Surgery, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA

    Ali A. Baaj

  4. Department of Radiation Oncology, NewYork-Presbyterian Hospital/Weill Cornell Medicine, New York, NY, USA

    Jonathan P.S. Knisely

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Rachner, T.D., Hofbauer, L.C., Göbel, A. (2020). Bone Metabolism in Cancer. In: Ramakrishna, R., Magge, R., Baaj, A., Knisely, J. (eds) Central Nervous System Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-42958-4_36

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  • DOI: https://doi.org/10.1007/978-3-030-42958-4_36

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-42957-7

  • Online ISBN: 978-3-030-42958-4

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