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Osteoporose beim Mann mit hormonablativer Therapie bei nicht-metastasiertem Prostatakarzinom

Osteoporosis in men receiving androgen deprivation therapy for non-metastatic prostate cancer

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Zusammenfassung

Die Osteoporose als ein systemischer Verlust des Knochenmineralgehaltes mit erhöhter Frakturinzidenz wurde bisher überwiegend bei Frauen untersucht. Sowohl das Auftreten von Wirbelkörper- und Schenkelhalsfrakturen als auch die damit verbundene Exzessmortalität ist bei Frauen und Männern nachgewiesenermaßen unterschiedlich. Ein der Menopause der Frau entsprechendes Syndrom mit Verlust des Serumtestosterons, „ADAM“ (androgen deficiency syndrome of the aging male) konnte bisher nicht schlüssig nachgewiesen werden. Demgegenüber führt der Verlust von Testosteron durch eine operative oder chemische Kastration bei Patienten mit Prostatakarzinom zu einer Abnahme des Knochenmineralgehaltes und einem erhöhten Frakturrisiko. Mehrere Therapieoptionen, wie z. B. Bisphosphonate, wurden in verschiedenen Interventionsstudien bei der Osteoporose unter hormonablativer Therapie erfolgreich eingesetzt und konnten die Knochendichte signifikant erhöhen. Als neue Therapieoptionen stehen Denosumab (monoklonaler Antikörper gegen RANK Ligand) und Toremifen (ein selektiver Östrogen-Rezeptor-Modulator) zur Verfügung. Beide konnten in kontrollierten Studien signifikant die Rate an Wirbelkörperfrakturen bei Patienten mit nicht-metastasiertem Prostatakarzinom unter einer jahrelangen hormonablativen Therapie reduzieren.

Summary

Osteoporosis is defined as a continuous loss of bone mineral density accompanied by an increased fracture risk in females and males. A fall of estrogen concentrations at the menopause and the consecutive rapid bone loss are an established pathogenic mechanism in female osteoporosis. Males do not have a menopause equivalent during which significant amounts of bone are lost. Several diseases, therapeutic strategies and nutritional deficiencies may also result in bone loss and reduced bone mineral density. Prostate cancer is the most common visceral malignancy in men. Suppression of endogenous androgen production as a therapeutic tool is commonly used in patients with non-metastatic prostate cancer and is associated with significant bone loss and an increased fracture risk.

Androgen deprivation therapy is prescribed both for men with locally advanced or high-risk non-metastatic prostate cancer. Osteoclast inhibition with any of several bisphosphonates improves bone mineral density and reduces fracture risk. Denosumab (a monoclonal antibody against RANK ligand) and toremifene (a selective estrogen receptor modulator) recently have been shown to be effective to reduce vertebral fractures in patients with non-metastatic prostate cancer receiving androgen-deprivation therapy. This overview focuses on cancer-treatment-induced bone loss in patients with non-metastatic prostate cancer.

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Literatur

  1. Kudlacek S, Resch H, Pietschmann P, et al. Hormones and osteoporosis in the aging male. Aging Male. 1999;2:145–50.

    Article  Google Scholar 

  2. Weitzmann MN, Pacifici R. Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest. 2006;116(5):1186–94.

    Article  PubMed  CAS  Google Scholar 

  3. Leidig-Bruckner G, Raue F, Frank-Raue K. Secondary osteoporosis – relevant clinical characteristics in diagnosis and therapy. Dtsch Med Wochenschr. 2012;137(7):326–32.

    Article  PubMed  CAS  Google Scholar 

  4. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000;343:604–10.

    Article  PubMed  CAS  Google Scholar 

  5. Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide Human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Miner Res. 2003;18:9–17.

    Article  PubMed  CAS  Google Scholar 

  6. Saad F, Adachi JD, Brown JP, et al. Cancer treatment-induced bone loss in breast and prostate cancer. J Clin Oncol. 2008;26:5465–76.

    Article  PubMed  Google Scholar 

  7. Stepan J, Lachmann M, Zverina J, et al. Castrated men exhibited bone loss. Effect of calcitonin treatment on biochemical indices of bone remodelling. J Clin Endocr. 1989;69:523–7.

    Article  PubMed  CAS  Google Scholar 

  8. Jeldres C, Isbarn H, Capitanio U, et al. A systematic analysis of the detrimental effect of orchiectomy on the skeletal condition of men with prostate cancer. J Urology. 2009;181:293–6.

    Article  Google Scholar 

  9. Shahinian V, Kuo Y, Freeman J, et al. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352:154–64.

    Article  PubMed  CAS  Google Scholar 

  10. Alibhai SM, Yun L, Cheung AM, et al. Screening for osteoporosis in men receiving androgen deprivation therapy. JAMA. 2012;307(3):255–6.

    Article  PubMed  CAS  Google Scholar 

  11. Pietschmann P, Gollob E, Brosch S, et al. The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism. Exp Gerontol. 2003;38:1119–27.

    Article  PubMed  CAS  Google Scholar 

  12. Kudlacek S, Schneider B, Woloszczuk W, et al. Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone. 2003;32:681–6.

    Article  PubMed  CAS  Google Scholar 

  13. Pietschmann P, Kudlacek S, Grisar J, et al. Bone turnover markers and sex hormones in men with idiopathic osteoporosis. Eur J Clin Invest. 2001;31:444–51.

    Article  PubMed  CAS  Google Scholar 

  14. Green CC, Hoeg Soerensen T, et al. Prevalence of low serum estradiol levels in male osteoporosis. Osteoporos Int. 2000;11:697–701.

    Article  Google Scholar 

  15. Smith M, Boyce S, Moyneur E, et al. Risk of clinical fractures after gonadotopin-releasing hormone agonist therapy for prostate cancer. J Urol. 2006;175:136–9.

    Article  PubMed  CAS  Google Scholar 

  16. Resch H, Gollob E, Kudlacek S, Pietschmann P. Osteoporosis in the man. Wien Med Wochenschr. 2001;151:457–63.

    PubMed  CAS  Google Scholar 

  17. Adler RA. Management of osteoporosis in men on androgen deprivation therapy. Maturitas. 2011;68:143–7.

    Article  PubMed  CAS  Google Scholar 

  18. Morgans AK, Hancock ML, Barnette KG, et al. Racial differences in bone mineral density and fractures in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2012;187:889–93.

    Article  PubMed  Google Scholar 

  19. Varsavsky M, Reyes-García R, Cortés-Berdonces M, García-Martin A, et al. Serum 25 OH vitamin D concentrations and calcium intake are low in patients with prostate cancer. Endocrinol Nutr. 2011;58(9):487–91.

    Article  PubMed  CAS  Google Scholar 

  20. Travis RC, Crowe FL, Allen NE, et al. Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Epidemiol. 2009;169(10):1223–32.

    Article  PubMed  Google Scholar 

  21. Sieber PR, Keiller DL, Kahnoski RJ, et al. Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol. 2004;171:2272–6.

    Article  PubMed  CAS  Google Scholar 

  22. Campbell SC, Bhoopalam N, Moritz TE, et al. The use of zoledronic acid in men receiving androgen deprivation therapy for prostate cancer with severe osteopenia or osteoporosis. Urology. 2010;75(5):1138–43.

    Article  PubMed  Google Scholar 

  23. Michaelson M, Kaufman D, Lee H, et al. Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol. 2007; 25(9):1038–42.

    Article  PubMed  CAS  Google Scholar 

  24. Greenspan S, Nelson J, Trump D, et al. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med. 2007;146(6):416–24.

    PubMed  Google Scholar 

  25. Planas J, Trilla E, Raventós C, Cecchini L, et al. Alendronate decreases the fracture risk in patients with prostate cancer on androgen-deprivation therapy and with severe osteopenia or osteoporosis. BJU Int. 2009;104(11):1637–40.

    Article  PubMed  CAS  Google Scholar 

  26. Izumi K, Mizokami A, Sugimoto K, et al. Risedronate prevents persistent bone loss in prostate cancer patients treated with androgen deprivation therapy: results of a 2-year follow-up study. Prostate Cancer Prostatic Dis. 2011;3:238–42.

    Article  Google Scholar 

  27. Body J, Bergmann P, Boonen S, et al. Management of cancer treatment – induced bone loss in early breast and prostate cancer – a consensus paper of Belgian Bone Club. Osteoporosis Int. 2007;18(11):1439–50.

    Article  CAS  Google Scholar 

  28. Maldonado-Gonzales E, Pietschmann P. An antibody against RANKL for the treatment of osteoporosis, inflammatory and malignant bone diseases. Wien Med Wochenschr. 2010;160(17–18):458–63.

    Article  PubMed  Google Scholar 

  29. Lee RJ, Saylor PJ, Smith MR. Treatment and prevention of bone complications from prostate cancer. Bone. 2011;48(1):88–95.

    Article  PubMed  CAS  Google Scholar 

  30. Baron R, Ferrari S, Russell R. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone. 2011;28(4): 677–92.

    Article  Google Scholar 

  31. Saylor PJ, Lee RJ, Smith MR. Emerging therapies to prevent skeletal morbidity in men with prostate cancer. J Clin Oncol. 2011;29(27):3705–14.

    Article  PubMed  Google Scholar 

  32. Smith MR, Egerdie B, Hernández Toriz N, et al. Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen-deprivation therapy of prostate cancer. N Engl J Med. 2009;36(1):745–55.

    Article  Google Scholar 

  33. Smith MR, Malkowicz SB, Brawer MK, et al. Toremifene decreases vertebral fractures in men younger than 80 years receiving androgen deprivation therapy for prostate cancer. J Urol. 2011;186(6):2239–44.

    Article  PubMed  CAS  Google Scholar 

  34. Orwoll E, Stubbe Teglbjaerg C, Langdahl B, et al. A phase 3 study of the efficacy and safety of denosumab in men with low bone mineral density: design of the ADAMO Trial. J Bone Mineral Res. 2011;26(Suppl 1). (#MO442).

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Die Autoren haben eine Unterstützung für ein Forschungsprojekt von der Firma Amgen erhalten.

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  1. Lehrkrankenhaus der Barmherzigen Brüder, Medizinische Abteilung, Johannes von Gott Platz 1, 1020, Wien, Österreich

    Stefan Kudlacek &  Thomas Puntus

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  1. Stefan Kudlacek
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Correspondence to Stefan Kudlacek.

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Kudlacek, S., Puntus, T. Osteoporose beim Mann mit hormonablativer Therapie bei nicht-metastasiertem Prostatakarzinom. Wien Med Wochenschr 162, 380–385 (2012). https://doi.org/10.1007/s10354-012-0106-z

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  • DOI: https://doi.org/10.1007/s10354-012-0106-z

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