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The Increasing Responsibility Of The Urologist In Maintaining Bone Health In Prostate Cancer Patients

The Increasing Responsibility Of The Urologist In Maintaining Bone Health In Prostate Cancer Patients. Kurt Miller Charité, Berlin. Osteroporosis on the Rise*. Increase of osteroporotic fractures in Finnland. Incidence / 100 000. +192 %. * Kannus P, Osteoporos int 2000.

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The Increasing Responsibility Of The Urologist In Maintaining Bone Health In Prostate Cancer Patients

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  1. The Increasing Responsibility Of The Urologist In Maintaining Bone Health In Prostate Cancer Patients Kurt Miller Charité, Berlin

  2. Osteroporosis on the Rise* Increase of osteroporotic fractures in Finnland Incidence / 100 000 +192 % * Kannus P, Osteoporos int 2000

  3. Prostate Cancer Bone Problems • Osteoporosis • Castration • Metastases

  4. Bone Density - Definitions • T-Score = Standard deviation from normal values • T-Score -1 bis – 2,5Osteopenia • T-Score < - 2,5Osteoporosis

  5. Bone Density - DXA

  6. Risk Factors for Osteoporosis • Study of 174 men with prostate cancer and 106 age-matched controls • Before receiving ADT, 73 (42%) patients were osteoporotic and 65 (37%) were osteopenic • Age correlated significantly with BMD • Smoking, family history of osteoporosis • Diagnosis of prostate cancer • Regardless of PSA, stage, grade Hussain SA, et al. BJU Int. 2003;92:690-694.

  7. Risk of Osteoporosis after LHRH Treatment In men osteopenic at baseline Weston R, et al. Presented at: British Association of Urological Surgeons Annual Meeting June 23-27, 2003; Manchester, UK.

  8. Changes in BMD During GnRH Agonist Treatment (12-Month Data) P < .001 Lumbar spine Total hip Mittan D, et al. J Clin Endocrinol Metab. 2002;87:3656-3661.

  9. ADT Decreases BMD after 1 Year Change from StudyNTreatment baseline BMD Eriksson et al111OrchiectomyHip: –9.6%Radius: –4.5% Maillefert et al212 GnRH agonist Hip: –3.9%L spine: –4.6% Daniell et al326 Orchiectomy or Hip: –2.4% GnRH agonist Berruti et al435 GnRH agonist Hip: –0.6%L spine: –2.3% 1Eriksson S, et al. Calcif Tissue Int. 1995; 57:97-99. 2Maillefert JF, et al. J Urol. 1999;161:1219-1222. 3Daniell HW, et al. J Urol. 2000;163:181-186.4Berruti A, et al. J Urol. 2002;167:2361-2367.

  10. Orchiectomy Control Androgen Deprivation Therapy Increases Fracture Risk 50 40 30 Cumulative fracture incidence (%) 20 10 0 0 1 2 3 4 5 6 7 8 9 Years Daniell HW. J Urol. 1997;157:439-444.

  11. Risk of Fracture After Androgen Deprivation for Prostate Cancer • Records of 50,613 men with prostate cancer between 1992 and 1997 • 19.4% of those who received ADT had a fracture compared with 12.6% of those not receiving ADT (P < .001) • Statistically significant relation between the number of doses of GNRH received and the subsequent risk of fracture ShahinianVB,etal.NEnglJMed.2005;352:154-164.

  12. Risk of Fracture After Androgen Deprivation for Prostate Cancer ReproducedwithpermissionfromShahinianVB,etal.NEnglJMed.2005;352:154-164.

  13. Prostate Cancer and Bone Loss • A significant number of prostate cancer patients present with bone loss prior to androgen deprivation therapy • Androgen deprivation results in a significant risk of further bone loss and increased fracture risk • BMD assessment prior to treatment and annually thereafter is recommended

  14. Can We Prevent Bone Loss Resulting From ADT?

  15. O H O P O H N O H O H O P O H Classes of Bisphosphonates etidronate pamidronate risedronate zoledronic acid alendronate clodronate tiludronate ibandronate

  16. pamidronate olpadronate alendronate risedronate ibandronate Zoledronicacid Potency of Bisphosphonates Potency relative to pamidronate in vivo(hypercalcaemic rat), linear scale1 1. Green J, et al. JBone Miner Res. 1994.

  17. Oral Etidronate and ADT-Induced Bone Loss N = 12 6 No etidronate Etidronate 4 2 0 Change in BMD (6 months) -2 –2.4* -4 -6 –6.5 -8 -10 Femoral neck DEXA *P = .02 Diamond T, et al. Cancer. 1998;83:1561-1566.

  18. Pamidronate in Patients with Prostate Cancer Receiving ADT Recurrent or locally advanced stage M0 prostate cancer (N = 47) Randomize GnRH agonist GnRH agonist + pamidronate Endpoints:Bone mineral density Biochemical markers of bone turnover Smith MR, et al. N Engl J Med. 2001;345:948-955.

  19. Pamidronate to Prevent Bone Loss During ADT *P < .005. Smith MR, et al. N Engl J Med. 2001;345:948-955.

  20. Zoledronic Acid in Patients with Prostate Cancer Receiving ADT US 705: Study Design Zoledronic acid 4 mg q 3 months R A N DO M I Z E D StartADT Placebo q 3 months < 30 days 12 months BaselineBMD End-of-study BMD Smith MR, et al. J Urol. 2003;169:2008-2012.

  21. Effect of Zoledronic Acid on Lumbar Spine BMD at 1 Year P < .001 8.4 7 P < .001 6.4 5.6 P < .001 4.4 3.9 LS mean percent change from baseline 2.4 0.4 -1.6 -1.9 -2.0 -2.7 -3.6 All GnRH GnRH + Antiandrogen Zoledronic acid Placebo Data from Smith MR, et al. J Urol. 2003;169:2008-2012.

  22. P < .001 Effect of Zoledronic Acid on Hip BMD at 1 Year P < .001 P < .001 Adapted with permission from Smith MR, et al. J Urol. 2003;169:2008-2012.

  23. Conclusions • A significant number of prostate cancer patients present with bone loss prior to androgen deprivation therapy • Osteopenic patients receiving ADT are at significant risk for further bone loss that may result in pathologic fracture • Bisphosphonates are effective at preserving BMD in patients receiving ADT

  24. BMD Should Be Assessed To Treat Osteoporosis and Prevent Fractures Any fracture after minimal trauma • Treatment of osteoporosis to prevent further fracture Ensure adequate calcium intake and correct vitamin status Confirm fracture on x-ray Suspected vertebral fracture • Assess BMD • DEXA • Hip • Radius • Lumbar spine • Quantitative CT • Lumbar spine T-score < –2.5 (osteoporosis) • Risk factors for fracture • ADT • Prior fracture Repeat BMDafter 6 to 12 months T-score 1.0 to –2.5 (osteopenia) T-score> 1.0 Repeat BMD after 2 years Adapted from Diamond TH, et al. Cancer. 2004;100:892-899.

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