Bone mineral density changes in patients who receive androgenic deprivation therapy for prostate cancer
Keywords:
PROSTATIC NEOPLASMS, ANDROGEN ANTAGONISTS, OSTEOPOROSIS
Abstract
Introduction: prostate cancer is the most frequent malignant tumor in men in Uruguay. Androgenic deprivation therapy (ADT) is a valuable tool to treat this condition. In spite of it being highly effective, this treatment has several non-desirable effects, a reduction in bone mineral density being among them.
Material: we conducted a longitudinal, observational and prospective study whose objective was to determine whether there is a reduction in bone mineral density in patients who receive ADT for prostate cancer. Patients who were carriers of prostate cancer undergoing any stage who would start their ADT treatment at the Oncology Unit of the University Hospital of Montevideo from September 2012 through August 2013 were included in the study. All of them underwent a bone densitometry prior to the initiation of ADT (BD1) treatment and it was repeated six months after they received the first dose of hormone treatment (BD2). Measurements of bone density were compared for every region analysed in g/ cm2 in BD1 versus BD2.
Results: Ten patients with an average age of 77 years old were followed-up. A significant reduction in bone mineral density was observed in the L3-L4 spinal segment (L3: 1.268 g/cm2 at 1.225 g/cm2 p=0.01; L4: 1.247g/cm2 at 1.227g/cm2 p=0.005), whereas in the other points assessed (L1, L2, femoral neck and total hip) there was a reduction as well, although it did not represent any statistical significance.
Conclusions: we confirmed ADT reduces the bone mineral density in lumbar vertebrae L3 and L4 in a relatively short time (six minths). This negative effect needs to be timely assessed, identified and prevented to avoid greater complications.
References
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(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.
(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.
Published
2015-12-31
How to Cite
1.
Acuña Tapia S, Fresco R, Acosta Naranjo W. Bone mineral density changes in patients who receive androgenic deprivation therapy for prostate cancer. Rev. Méd. Urug. [Internet]. 2015Dec.31 [cited 2024Dec.18];31(4):249-58. Available from: https://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/191
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