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Bone-Targeted Therapies in Adjuvant Setting

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Management of Bone Metastases

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Abstract

Improvement in the understanding of bone disease biology has led to the development of bone-targeted agents (BTAs). The most widely used BTAs are bisphosphonates, which are inhibitors of osteoclastogenesis and osteoclast activation, and the new bone-targeted therapy, which is denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand (RANKL).

Breast cancer and prostate cancer represent the most common cancers with a high incidence of bone metastasis in their disease clinical course and in which there are several trials investigating bone health in adjuvant setting. Furthermore, it has become clear that the bone homeostasis is fundamental for the optimal management of breast cancer and prostate cancer at any stages, to prevent skeletal fractures.

The routine clinical use of BTAs in adjuvant setting is still controversial, even though evidences showed that targeting bone-cell function can provide a potential additional approach to preventing systemic relapse as a component of standard adjuvant therapy.

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References

  1. Ibrahim T, Farolfi A, Mercatali L, Ricci M, Amadori D. Metastatic bone disease in the era of bone-targeted therapy: clinical impact. Tumori. 2013;99(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  2. Coleman RE. Risks and benefits of bisphosphonates. Br J Cancer. 2008;98(11):1736–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. D'Oronzo S, Stucci S, Tucci M, Silvestris F. Cancer treatment-induced bone loss (CTIBL): pathogenesis and clinical implications. Cancer Treat Rev. 2015;41(9):798–808.

    Article  CAS  PubMed  Google Scholar 

  4. Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M, Lee K-A, Zheng M, Hei Y-J, Coleman RE. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005;97:59–69.

    Article  CAS  PubMed  Google Scholar 

  5. Gnant M, Mlineritsch B, Stoeger H, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group trial 12. Ann Oncol. 2015;26:313–20.

    Article  CAS  PubMed  Google Scholar 

  6. Gnant M. Role of bisphosphonates in postmenopausal women with breast cancer. Cancer Treat Rev. 2014;40:476–84.

    Article  CAS  PubMed  Google Scholar 

  7. Yoneda T, Hiraga T. Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun. 2005;328(3):679–87.

    Article  CAS  PubMed  Google Scholar 

  8. Ibrahim T, Flamini E, Mercatali L, Sacanna E, Serra P, Amadori D. Pathogenesis of osteoblastic bone metastases from prostate cancer. Cancer. 2010;116(6):1406–18. Erratum in: Cancer. 2010 May 15;116(10):2503

    Article  CAS  PubMed  Google Scholar 

  9. Lories RJ, Luyten FP. Osteoprotegerin and osteoprotegerin-ligand balance: a new paradigm in bone metabolism providing new therapeutic targets. Clin Rheumatol. 2001;20:3–9.

    Article  CAS  PubMed  Google Scholar 

  10. Hofbauer LC, Neubader A, Heufelder AE. Receptor activator of nuclear factor-kb ligand and osteoprotegerin. Cancer. 2001;92:460–70.

    Article  CAS  PubMed  Google Scholar 

  11. Shapiro CL. Bisphosphonates in breast cancer patients with skeletal metastases. Hematol Oncol Clin North Am. 1994;8:153–63.

    Article  CAS  PubMed  Google Scholar 

  12. Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 2000;88:2961–78.

    Article  CAS  PubMed  Google Scholar 

  13. Roelofs AJ, Thompson K, Gordon S, Rogers MJ. Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res. 2006;12:6222s–30s.

    Article  CAS  PubMed  Google Scholar 

  14. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19:1059–66.

    Article  CAS  PubMed  Google Scholar 

  15. Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappa B ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res. 2006;12:1221–8.

    Article  CAS  PubMed  Google Scholar 

  16. Fromigue O, Lagneaux L, Body JJ. Bisphosphonates induce breast cancer cell death in vitro. J Bone Miner Res. 2000;15:2211–21.

    Article  CAS  PubMed  Google Scholar 

  17. Senaratne SG, Pirianov G, Mansi JL, Arnett TR, Colston KW. Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000;82:1459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Verdijk R, Franke HR, Wolbers F, Vermes I. Differential effects of bisphosphonates on breast cancer cell lines. Cancer Lett. 2007;246:308–12.

    Article  CAS  PubMed  Google Scholar 

  19. Mercatali L, Spadazzi C, Miserocchi G, Liverani C, De Vita A, Bongiovanni A, Recine F, Amadori D, Ibrahim T. The effect of everolimus in an in vitro model of triple negative breast cancer and osteoclasts. Int J Mol Sci. 2016;17(11):E1827.

    Article  CAS  PubMed  Google Scholar 

  20. Associazione Italiana di Oncologia Medica (AIOM) guidelines 2016.

    Google Scholar 

  21. Body JJ, Bergmann P, Boonen S, et al. Management of cancer treatment-induced bone loss in early breast and prostate cancer—a consensus paper of the Belgian Bone Club. Osteoporos Int. 2007;18:1439–50.

    Article  CAS  PubMed  Google Scholar 

  22. Reid DM, Doughty J, Eastell R, et al. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Cancer Treat Rev. 2008;34(Suppl 1):S3–S18.

    Article  CAS  PubMed  Google Scholar 

  23. Lee CE, Leslie WD, Czaykowski P, et al. A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy. Curr Oncol. 2011;18:e163–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Coleman R, Body JJ, Aapro M, Hadji P, J. Herrstedt on behalf of the ESMO Guidelines Working Group Bone health in Cancer Patients. ESMO clinical practice guidelines. Ann Oncol. 2014;25(Supplement 3):iii124–37.

    Article  PubMed  Google Scholar 

  25. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  PubMed  Google Scholar 

  26. Brufsky A. Cancer treatment-induced bone loss: pathophysiology and clinical perspectives. Oncologist. 2008;13:187–95.

    Article  CAS  PubMed  Google Scholar 

  27. Gnant M, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy. Lancet Oncol. 2008;9:840–9.

    Article  CAS  PubMed  Google Scholar 

  28. Hirbe A, Morgan EA, Uluçkan Ö, Weilbaecher K. Skeletal complications of breast cancer therapies. Clin Cancer Res. 2006;12(20 Pt 2):6309s–14s.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cuzick J, Forbes J, Edwards R, et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet. 2002;360:817–24.

    Article  CAS  PubMed  Google Scholar 

  30. Cosman F. Selective estrogen-receptor modulators. Clin Geriatr Med. 2003;19:371–9.

    Article  PubMed  Google Scholar 

  31. Powles TJ, Hickish T, Kanis JA, Tidy A, Ashley S. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol. 1996;14:78–84.

    Article  CAS  PubMed  Google Scholar 

  32. Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med. 1992;326:852–6.

    Article  CAS  PubMed  Google Scholar 

  33. Kristensen B, Ejlertsen B, Dalgaard P, et al. Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study. J Clin Oncol. 1994;12:992–7.

    Article  CAS  PubMed  Google Scholar 

  34. Eastell R, Adams JE, Coleman RE, et al. Effect of anastrozole on bone mineral density: 5-year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol. 2008;26:1051–7.

    Article  CAS  PubMed  Google Scholar 

  35. Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98:1802–10.

    Article  CAS  PubMed  Google Scholar 

  36. Eastell R, Hannon RA, Cuzick J, et al. Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). J Bone Miner Res. 2006;21:1215–23.

    Article  CAS  PubMed  Google Scholar 

  37. Eastell R, Adams J. Results of the ‘Arimidex’ (anastrozole, A), Tamoxifen (T), Alone or in Combination (C) (ATAC) trial: Effects on bone mineral density (BMD) and bone turnover (ATAC Trialists’ Group). In: Presented at the 27th Congress of the European Society for Medical Oncology, Nice, 711, 18–22 Oct 2002.

    Google Scholar 

  38. Coleman RE, Body J-J, Gralow JR, Lipton A. Bone loss in patients with breast cancer receiving aromatase inhibitors and associated treatment strategies. Cancer Treat Rev. 2008;34(Suppl 1):S31–42.

    Article  CAS  PubMed  Google Scholar 

  39. Coombes RC, Hall E, Gibson L, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081–92.

    Article  CAS  PubMed  Google Scholar 

  40. Coombes RC, Hall E, Snowdon CF, Bliss JM. The Intergroup Exemestane Study: a randomized trial in postmenopausal patients with early breast cancer who remain disease-free after two to three years of tamoxifen-updated survival analysis. Breast Cancer Res Treat. 2004;88(suppl 1):S7.

    Google Scholar 

  41. Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007;369:559–70.

    Article  CAS  PubMed  Google Scholar 

  42. Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386:433–43.

    Article  CAS  PubMed  Google Scholar 

  43. Soiland H, Hagen KB, Gjerde J, Lende TH, Lien EA. Breaking away: high fracture rates may merit a new trial of adjuvant endocrine therapy in Scandinavian breast cancer patients. Acta Oncol. 2013;52:861–2.

    Article  PubMed  Google Scholar 

  44. Early Breast Cancer Trialists Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386:1341–52.

    Article  CAS  Google Scholar 

  45. Lester J, Dodwell D, McCloskey E, Coleman R. The causes and treatment of bone loss associated with carcinoma of the breast. Cancer Treat Rev. 2005;31:115–42.

    Article  PubMed  Google Scholar 

  46. Wilson C, Coleman R. Adjuvant bone-targeted therapies for postmenopausal breast cancer. JAMA Oncol. 2016;2(4):423–4.

    Article  PubMed  Google Scholar 

  47. Cheung AM, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. Lancet Oncol. 2012;13:275–84.

    Article  CAS  PubMed  Google Scholar 

  48. Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, Grampp S, Kaessmann H, Schmid M, Menzel C, Piswanger-Soelkner JC, Galid A, Mittlboeck M, Hausmaninger H, Jakesz R. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2007;25:820–8.

    Article  CAS  PubMed  Google Scholar 

  49. Lester JE, Dodwell D, Purohit O, Gutcher SA, Ellis SP, Thorpe R. Prevention of anastrozole-induced bone loss with oral monthly ibandronate during aromatase inhibitor therapy for breast cancer. Clin Cancer Res. 2008;14:6336–42.

    Article  CAS  PubMed  Google Scholar 

  50. Lester JE, Dodwell D, et al. Prevention of anastrozole induced bone loss with monthly oral ibandronate: final 5 year results from the ARIBON trial. J Bone Oncol. 2012;1(2):57–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Van Poznak C, Hannon RA, Clack G, Campone M, Mackey JR, Apffelstaedt J, Eastell R. The SABRE (Study of Anastrozole with the Bisphosphonate RisedronatE) study: 12 month analysis. Breast Cancer Res Treat. 2007;106(suppl 1):S37.

    Google Scholar 

  52. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–65.

    Article  CAS  PubMed  Google Scholar 

  53. Diel IJ, Jaschke A, Solomayer EF, et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow-a long-term follow-up. Ann Oncol. 2008;19:2007–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Powles TJ, Paterson A, McCloskey E, et al. Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer. Breast Cancer Res Treat. 2006;8:R13.

    Article  CAS  Google Scholar 

  55. Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009;360:679–91.

    Article  CAS  PubMed  Google Scholar 

  56. Coleman RE, Marshall H, Cameron D, AZURE Investigators, et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011;365(15):1396–405.

    Article  CAS  PubMed  Google Scholar 

  57. Brufsky AM, Bosserman LD, Caradonna RR, et al. Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results. Clin Breast Cancer. 2009;9:77–85.

    Article  CAS  PubMed  Google Scholar 

  58. Coleman R, de Boer R, Eidtmann H, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-fast study): final 60-month results. Ann Oncol. 2013;24:398–405.

    Article  CAS  PubMed  Google Scholar 

  59. von Minckwitz G, et al. German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer. J Clin Oncol. 2013;31:3531–9.

    Article  Google Scholar 

  60. Paterson AH, Anderson SJ, Lembersky BC, Fehrenbacher L, Falkson CI, King KM, Weir LM, Brufsky AM, Dakhil S, Lad T, Baez-Diaz L, Gralow JR, Robidoux A, Perez EA, Zheng P, Geyer CE Jr, Swain SM, Costantino JP, Mamounas EP, Wolmark N. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol. 2012;13(7):734–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). 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 

  62. Gralow JBW, Paterson AHG, Lew D, et al. Phase III trial of bisphosphonates as adjuvant therapy in primary breast cancer: SWOG/Alliance/ECOG-ACRIN/NCIC Clinical Trials Group/NRG oncology study S0307 [abstract 558]. J Clin Oncol. 2014;32(5(suppl)).

    Google Scholar 

  63. Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1941;1:293–7.

    CAS  Google Scholar 

  64. Heidenreich A, Pfister D, Ohlmann CH, Engelmann UH. Androgen deprivation for advanced prostate cancer. Urol A. 2008;47(3):270–83.

    Article  CAS  Google Scholar 

  65. Denis LJ, Keuppens F, Smith PH, EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center, et al. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. Eur Urol. 1998;33:144–51.

    Article  CAS  PubMed  Google Scholar 

  66. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. JAMA. 2005;294(2):238–44.

    Article  CAS  PubMed  Google Scholar 

  67. Bastiana PJ, Boorjian SA, Bossi A, et al. High-risk prostate cancer: from definition to contemporary management. Eur Urol. 2012;61(6):1096.

    Article  Google Scholar 

  68. D’Amico AV, Cote K, Loffredo M, et al. Determinants of prostate cancer specific survival after radiation therapy for patients with clinically localized prostate cancer. J Clin Oncol. 2002;20:4567–73.

    Article  PubMed  Google Scholar 

  69. Kattan MW, Eastham JA, Stapleton AM, Wheeler TM, Scardino PT. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst. 1998;90:766–71.

    Article  CAS  PubMed  Google Scholar 

  70. Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21(2):115–37.

    PubMed  CAS  Google Scholar 

  71. Higano CS. Bone loss and the evolving role of bisphosphonate therapy in prostate cancer. Urol Oncol. 2003;21(5):392–8.

    Article  CAS  PubMed  Google Scholar 

  72. Galvão DA, Spry NA, Taaffe DR, et al. Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int. 2008;102:44–7.

    Article  PubMed  Google Scholar 

  73. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999;353(9156):878–82.

    Article  CAS  PubMed  Google Scholar 

  74. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352(2):154–64.

    Article  CAS  PubMed  Google Scholar 

  75. Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW, Finkelstein JS. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med. 2001;345(13):948–55.

    Article  CAS  PubMed  Google Scholar 

  76. Lipton A, Small E, Saad F, et al. The new bisphosphonate, zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Investig. 2002;20(suppl 2):45–54.

    Article  CAS  Google Scholar 

  77. Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003;169(6):2008–12.

    Article  CAS  PubMed  Google Scholar 

  78. Dearnaley DP, Mason MD, Parmar MK, Sanders K, Sydes MR. Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials. Lancet Oncol. 2009;10(9):872–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Smith MR, Halabi S, Ryan CJ, et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014;32:1143–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wirth M, Tammela T, Cicalese V, Gomez Veiga F, Delaere K, Miller K, Tubaro A, Schulze M, Debruyne F, Huland H, Patel A, Lecouvet F, Caris C, Witjes W. Prevention of bone metastases in patients with high-risk nonmetastatic prostate cancer treated with zoledronic acid: efficacy and safety results of the Zometa European Study (ZEUS). Eur Urol. 2015;67(3):482–91.

    Article  CAS  PubMed  Google Scholar 

  82. Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C, Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chen Y, Sawyers CL, Scher HI. Targeting the androgen receptor pathway in prostate cancer. Curr Opin Pharmacol. 2008;8(4):440–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, Wynne C, Murray R, Zinner NR, Schulman C, Linnartz R, Zheng M, Goessl C, Hei YJ, Small EJ, Cook R, Higano CS. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918–25.

    Article  PubMed  Google Scholar 

  85. Smith MR, Saad F, Coleman R, 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 

  86. Ibrahim T, Barbanti F, Giorgio-Marrano G, et al. Osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: a retrospective study. Oncologist. 2008;13(3):330–6.

    Article  CAS  PubMed  Google Scholar 

  87. European Medicines Agency. Xgeva (denosumab) summary of product characteristics. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Product_Information/human/002173/WC500110381.pdf.

  88. Saad F, Brown JE, Van Poznak C, et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2012;23:1341–7.

    Article  CAS  PubMed  Google Scholar 

  89. Migliorati CA, Epstein JB, Abt E, Berenson JR. Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review. Nat Rev Endocrinol. 2011;7:34–42.

    Article  CAS  PubMed  Google Scholar 

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  1. Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura di Tumori (IRST) IRCCS, Meldola, Forlì-Cesena, Italy

    Toni Ibrahim & Federica Recine

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  1. Department of Orthopaedics and Trauma Surgery, University Campus Bio-Medico of Rome, Rome, Italy

    Vincenzo Denaro

  2. Department of Orthopaedics and Trauma Surgery, University Campus Bio-Medico of Rome, Rome, Italy

    Alberto Di Martino

  3. General Direction of Health Program, National Ministry of Health of Italy, Rome, Italy

    Andrea Piccioli

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Ibrahim, T., Recine, F. (2019). Bone-Targeted Therapies in Adjuvant Setting. In: Denaro, V., Di Martino, A., Piccioli, A. (eds) Management of Bone Metastases. Springer, Cham. https://doi.org/10.1007/978-3-319-73485-9_3

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