Cambios en la densidad mineral ósea en pacientes que reciben terapia de deprivación androgénica para el cáncer de próstata
Palabras clave:
NEOPLASIAS DE LA PRÓSTATA, ANTAGONISTAS DE ANDRÓGENOS, OSTEOPOROSISResumen
Introducción: el cáncer de próstata (CP) es el tumor maligno más frecuente en hombres en Uruguay. La terapia de deprivación androgénica (TDA) es una herramienta valiosa para su tratamiento. Si bien es altamente eficaz, este tratamiento tiene diversos efectos no deseados, entre los que se encuentra la disminución de la densidad mineral ósea.
Material y método: realizamos un estudio longitudinal, observacional y prospectivo cuyo objetivo fue determinar si existe disminución de la densidad mineral ósea en los pacientes que reciben TDA para el CP. Se incluyeron pacientes portadores de CP en cualquier estadio que iniciarían tratamiento con TDA en el Servicio de Oncología del Hospital de Clínicas de Montevideo, Uruguay, en el período setiembre de 2012 a agosto de 2013, en quienes se realizó una densitometría ósea (DMO) previo al inicio de la TDA (DMO1) y se repitió a los seis meses de recibir la primera dosis de tratamiento hormonal (DMO2). Para cada región analizada se compararon las medias de densidad ósea medida en g/cm2 en la DMO1 vs DMO2.
Resultados: se hizo seguimiento a diez pacientes con una edad mediana de 77 años. Se observó disminución significativa de la densidad mineral ósea en vértebras L3 y L4 (L3: 1.268 g/cm2 a 1.225 g/cm2 p=0,01; L4: 1.247 g/cm2 a 1.227g/cm2 p=0,005), mientras que en los otros puntos evaluados (L1, L2, cuello de fémur y cadera total) también hubo una disminución pero sin alcanzar significancia estadística.
Conclusiones: confirmamos que la TDA disminuye la densidad mineral ósea por lo menos en vértebras lumbares 3 y 4 en un relativamente corto plazo (seis meses). Este efecto adverso debe evaluarse, identificarse y prevenirse oportunamente para evitar complicaciones mayores.
Citas
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(34) Aldabe M. Márquez M. Primer encuesta nacional de consumo de lácteos en niños de 1º, 3º y 6º año de las escuelas públicas uruguayas. Montevideo: ANEP, 2006.
(35) Mendoza B. Deficiencia de Vitamina D: guías clínicas para su diagnóstico y tratamiento. Tendencias Med 2013; 21(42): 149-58.
(36) Uruguay. Universidad de la República. Facultad de Medicina. Hospital de Clínicas. Cátedra de Oncología Clínica. Servicio de Oncología Clínica. Pautas de oncologia médica para el diagnóstico, tratamiento sistémico y seguimiento. Montevideo: Facultad de Medicina, 2012.
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(38) Food and Drugs Administration. Food and Nutrition Board. Dietary reference intakes for calcium, phosphorous, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press, 2010.
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(40) Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96(7):1911-30.
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(42) Zheng Y, Zhu J, Zhou M, Cui L, Yao W, Liu Y. Meta-analysis of long-term vitamin D supplementation on overall mortality. PLoS One 2013; 8(12):e82109.
(43) Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001; 345(13):948-55.
(44) 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.
(2) Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al; European Association of Urology. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65(2):467-79.
(3) Arroyo J, Soto E, Muñoz M, Contreras J, Varela J. Bloqueo androgénico en cáncer de próstata: revisión de la literatura. Rev Mex Urol 2012; 72(4):182-96.
(4) Lee, R, Saylor P, Smith M. Treatment and prevention of bone complications from prostate. Bone 2011; 48(1):88-95.
(5) Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev 2007; 28(7):778-808.
(6) Guyton A, Hall J. Tratado de fisiología médica. 12 ed. Madrid: Elsevier, 2011:955-72.
(7) Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer 2001; 1(1):34-45.
(8) Chen Y, Sawyers CL, Scher HI. Targeting the androgen receptor pathway in prostate cancer. Curr Opin Pharmacol 2008; 8(4):440-8.
(9) Roach M 3rd, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 2008; 26(4):585-91.
(10) Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011; 365(2):107-18.
(11) Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360(9327):103-6.
(12) Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 2010; 11(11):1066-73.
(13) Chen Y, Clegg NJ, Scher HI. Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target. Lancet Oncol 2009; 10(10):981-91.
(14) Chillik C, Acosta A. The role of LHRH agonists and antagonists. Reprod Biomed Online 2001; 2(2):120-8.
(15) NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7-29, 2000: highlights of the conference. South Med J 2001; 94(6):569-73.
(16) Wirth MP, Hakenberg OW, Froehner M. Antiandrogens in the treatment of prostate cancer. Eur Urol 2007; 51(2):306-13.
(17) Al-Shamsi HO, Lau AN, Malik K, Alamri A, Ioannidis G, Corbett T, et al. The current practice of screening, prevention, and treatment of androgen-deprivation-therapy induced osteoporosis in patients with prostate cancer. J Oncol 2012; 2012:958596.
(18) Yee EF, White RE, Murata GH, Handanos C, Hoffman RM. Osteoporosis management in prostate cancer patients treated with androgen deprivation therapy. J Gen Intern Med 2007; 22(9):1305-10.
(19) Sullivan S, Wagner J, Resnick NM, Nelson J, Perera SK, Greenspan SL. Vertebral fractures and the misclassification of osteoporosis in men with prostate cancer. J Clin Densitom 2011; 14(3):348-53.
(20) Drnovsek M, Echín M, Ercolano M, Rubín Z. Prevención y tratamiento de la osteoporosis en cáncer de próstata. Rev Argent Endocrinol Metab 2011; 48(4):225-34.
(21) Kabir S, Mancuso P, Rashid P. Androgen deprivation therapy—managing side effects. Aust Fam Physician 2008; 37(8):641-6.
(22) McLeod N, Huynh CC, Rashid P. Osteoporosis from androgen deprivation therapy in prostate cancer treatment. Aust Fam Physician 2006; 35(4):243-5.
(23) VanderWalde A, Hurria A. Aging and osteoporosis in breast and prostate cancer. CA Cancer J Clin 2011; 61(3): 139-56.
(24) Morote J, Planas J. Pérdida de masa ósea en pacientes con cáncer de próstata sometidos a deprivación androgénica. Actas Urol Esp 2011; 35(4):232-9.
(25) Abrahamsen B, Nielsen MF, Eskildsen P, Andersen JT, Walter S, Brixen K. Fracture risk in Danish men with prostate cancer: a nationwide register study. BJU Int 2007; 100(4):749-54.
(26) Wadhwa VK, Weston R, Mistry R, Parr NJ. Long-term changes in bone mineral density and predicted fracture risk in patients receiving androgen-deprivation therapy for prostate cancer, with stratification of treatment based on presenting values. BJU Int 2009; 104(6):800-5.
(27) Alibhai SM, Gogov S, Allibhai Z. Long-term side effects of androgen deprivation therapy in men with non-metastatic prostate cancer: a systematic literature review. Crit Rev Oncol Hematol 2006; 60(3):201-15.
(28) European Prospective Osteoporosis Study (EPOS) Group. Incidence of vertebral fracture in Europe: results from the European Prospective Osteoporosis Study (EPOS). J Bone Miner Res 2002; 17(4):716-24.
(29) 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.
(30) The International Society for Clinical Densitometry. 2015 ISCD Adult Official Positions. Middletown, CT: ISCD, 2015. Disponible en: http://www.iscd.org/official-positions/6th-iscd-position-development-conference-adult/. Consulta: 19 mayo 2015.
(31) Tenenhouse A, Joseph L, Kreiger N, Poliquin S, Murray TM, Blondeau L, et al; CaMos Research Group. Canadian Multicentre Osteoporosis Study. Estimation of the prevalence of low bone density in Canadian women and men using a population-specific DXA reference standard: the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 2000; 11(10):897-904.
(32) El-Desouki MI, Sulimani RA. High prevalence of osteoporosis in Saudi men. Saudi Med J 2007; 28(5):774-7.
(33) Jiang HX, Majumdar SR, Dick DA, Moreau M, Raso J, Otto DD, et al. Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J Bone Miner Res 2005; 20(3):494-500.
(34) Aldabe M. Márquez M. Primer encuesta nacional de consumo de lácteos en niños de 1º, 3º y 6º año de las escuelas públicas uruguayas. Montevideo: ANEP, 2006.
(35) Mendoza B. Deficiencia de Vitamina D: guías clínicas para su diagnóstico y tratamiento. Tendencias Med 2013; 21(42): 149-58.
(36) Uruguay. Universidad de la República. Facultad de Medicina. Hospital de Clínicas. Cátedra de Oncología Clínica. Servicio de Oncología Clínica. Pautas de oncologia médica para el diagnóstico, tratamiento sistémico y seguimiento. Montevideo: Facultad de Medicina, 2012.
(37) Kanis JA. World Health Organization Scientific Group. Assessment of osteoporosis at the primary health-care level: technical report. Geneva: WHO; 2007.
(38) Food and Drugs Administration. Food and Nutrition Board. Dietary reference intakes for calcium, phosphorous, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press, 2010.
(39) Michaëlsson K, Melhus H, Warensjö Lemming E, Wolk A, Byberg L. Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study. BMJ 2013; 346:f228.
(40) Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96(7):1911-30.
(41) Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293(18):2257-64.
(42) Zheng Y, Zhu J, Zhou M, Cui L, Yao W, Liu Y. Meta-analysis of long-term vitamin D supplementation on overall mortality. PLoS One 2013; 8(12):e82109.
(43) Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001; 345(13):948-55.
(44) 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.
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2015-12-31
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Acuña Tapia S, Fresco R, Acosta Naranjo W. Cambios en la densidad mineral ósea en pacientes que reciben terapia de deprivación androgénica para el cáncer de próstata. Rev. Méd. Urug. [Internet]. 31 de diciembre de 2015 [citado 23 de noviembre de 2024];31(4):249-58. Disponible en: https://revista.rmu.org.uy/index.php/rmu/article/view/191
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