1 / 27

Androgen Deprivation Therapy and Bone Loss in Men With Prostate Cancer

Androgen Deprivation Therapy and Bone Loss in Men With Prostate Cancer. William K. Oh, MD Associate Professor of Medicine Harvard Medical School Clinical Director, Lank Center for GU Oncology Dana-Farber Cancer Institute Boston, Massachusetts. Osteoporosis.

oriole
Download Presentation

Androgen Deprivation Therapy and Bone Loss in Men With Prostate Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Androgen Deprivation Therapy and Bone Loss in Men With Prostate Cancer • William K. Oh, MD • Associate Professor of Medicine • Harvard Medical School • Clinical Director, Lank Center for GU Oncology • Dana-Farber Cancer Institute • Boston, Massachusetts

  2. Osteoporosis National Institutes of Health Consensus Definition • “Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture.” • Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus • Statement Online. 2000 March 27-29;17[27-29;17:1-36].

  3. Osteoporosis in Men in the United States • 2 million men with osteoporosis • 8 million men with osteopenia • 1 in 4 lifetime fracture risk for men over the age of 50 years • Disease Statistics: Fast Facts. Washington, DC: National • Osteoporosis Foundation.

  4. Diagnosis of Bone Loss • Bone mineral density (BMD) testing • DEXA (dual-energy x-ray absorptiometry) scan • Quantitative CT (computed tomography) scan or ultrasound • WHO-defined T-score (SD below normal) • Normal: +1 < T ≤ -1 • Osteopenia: -1 < T < -2.5 • Osteoporosis: T ≤ -2.5

  5. Causes of Acquired Osteoporosis in Men • Older age • Smoking • Alcohol abuse • Inactive lifestyle • Chronic glucocorticoid therapy • Hypogonadism • Low testosterone and estrogen • Disease Statistics: Fast Facts. Washington, DC: National • Osteoporosis Foundation.

  6. Increasing Androgen Deprivation Therapy (ADT) Use • Barry MJ, et al. BJU Int. 2006;98:973-978.

  7. Hot flashes Loss of libido Weight gain Decreased muscle mass Accelerated osteoporosis Increased bone fractures Decreased cognitive function Increased diabetes mellitus Altered lipid profile Increased cardiovascular risk ADT Toxicity Is Significant

  8. 2 1 0 -1 -2 -3 -4 -5 LHRH Agonists Decrease BMD in Men With Prostate Cancer % Change in Bone Mineral Density Control LHRHAgonist P < .001 for each comparison 12-month data Lumbar Spine Total Hip • Mittan D, et al. J Clin Endocrinol Metab. 2002;87:3656-3661.

  9. Relationship Between BMD and Rates of Vertebral Fracture • Eastell R. N Engl J Med. 1998;338:736-746.

  10. Proportion of Men With Fractures1-5 Years After Cancer Diagnosis +6.8%; P < .001 21 ADT (n = 6650) 18 No ADT (n = 20,035) 19.4 15 12 12.6 Frequency (%) +2.8%; P < .001 9 6 5.2 3 2.4 0 Any Fracture Fracture Resulting in Hospitalization • Shahinian VB, et al. N Engl J Med. 2005;352:154-164.

  11. 100 90 80 70 60 50 40 1 2 3 4 5 6 7 8 9 10 Fracture-Free Survival Decreases With Cumulative ADT Exposure No androgen deprivation (n = 32,931) LHRH agonist, 1-4 doses (n = 3763) Unadjusted Fracture-Free Survival (%) LHRH agonist,5-8 doses(n = 2171) LHRH agonist,≥ 9 doses(n = 5061) Orchiectomy(n = 3399) Years After Diagnosis • Shahinian VB, et al. N Engl J Med. 2005;352:154-164.

  12. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 20 40 60 80 100 120 140 160 180 200 Fractures and Increased Mortality in Patients With Prostate Cancer Overall Survival N = 195 Cumulative Proportion Surviving No history of fracture (P = .04, log rank) History of fracture Months • Oefelein MG, et al. J Urol. 2002;168:1005-1007.

  13. Prevention of Bone Loss in Patients Receiving ADT • Men on ADT should take calcium 1200-1500 mg/day and vitamin D 800-1000 IU/day • A series of trials have shown that bisphosphonates can prevent bone loss associated with ADT use • Pamidronate • Zoledronic acid every 3 months and annually • Alendronate

  14. Pamidronate Prevents Bone Loss During LHRH Agonist Therapy N = 47 P < .005 for each comparison 12-month data Lumbar Spine Total Hip • Smith MR, et al. N Engl J Med. 2001;345:948-955.

  15. Quarterly Zoledronic AcidIncreases BMD During LHRH Agonist Therapy N = 106 P < .001 for each comparison Lumbar spine Total hip 12-month data • Smith MR, et al. J Urol. 2003;169:2008-2012.

  16. Annual Zoledronic Acid Increases BMD During LHRH Agonist Therapy N = 40 P < .005 for each comparison Lumbar spine Total hip 12-month data • Michaelson MD, et al. J Clin Oncol. 2006;25:1038-1042.

  17. Alendronate to Prevent Bone Loss During LHRH Agonist Therapy N = 112 P < .05 for each comparison Lumbar spine Total hip 12-month data • LHRH = luteinizing hormone-releasing hormone • Greenspan SL, et al. Ann Intern Med. 2008;146:416-424.

  18. Risks of Bisphosphonates • Flu-like symptoms (myalgias, fever) • Nausea • Fatigue • Renal toxicity • Osteonecrosis of the jaw

  19. Estrogens Regulate BMD • ADT causes severe estrogen deficiency • Lower estrogen levels lead to decreased BMD • Selective estrogen receptor modulators (SERMs) activate ER-alpha in bone and increase BMD in castrated men

  20. Raloxifene Increases BMD During LHRH Agonist Therapy P = .07 P < .001 N = 48 12-month data Lumbar spine Total hip • Smith MR, et al. J Clin Endocrinol Metab. 2004;89:3841-3846.

  21. Toremifene Fracture Prevention Study Toremifene daily for 2 years R A N D O M I Z E Current androgen deprivation therapy for prostate cancer; Age > 70 or low BMD (n = 1382) Placebo daily for 2 years Primary Endpoint:Incident vertebral fractures Secondary Endpoints: BMD, lipids, breast symptoms, hot flashes

  22. Toremifene 80 mg Increases Bone Mineral Density P < .001 P = .001 12-month data Lumbar spine Total hip • Smith MR, et al. J Urol. 2008;179:152-155.

  23. Toremifene Decreases Risk for New Vertebral Fractures Relative risk 0.46 (95% CI 0.22, 0.95) P = .032 Smith MR, et al. Proceedings of the 99th Annual Meeting of the AACR. Abstract LB-241.

  24. Increased Risk for Venous Thromboembolic Events (VTE) • Major risk factors include: > 80 years of age, history of VTE, recent surgery, recent bone fracture, and immobilization. • Minor risk factors include: megestrol acetate use, metastatic disease, hypertension, hypercholesterolemia, cigarette smoking, obesity, diabetes.

  25. Summary • ADT predisposes to loss of bone mineral density and fractures • Treatment with bisphosphonates and SERMs is effective in preventing bone loss and, in some studies, fractures • Optimal timing of therapy remains uncertain and requires taking into account baseline BMD, underlying risks, and planned duration of ADT

  26. Suggestions • Baseline DEXA in men initiating ADT • Calcium/vitamin D supplements • Exercise; alcohol and smoking cessation • Treat osteoporosis with bisphosphonates • Consider treating osteopenia if starting long-term ADT with fracture risks • Monitor BMD every 1-2 years

  27. Management of Bone Health in Patients on ADT Saad F, et al. J Clin Oncol. 2008;26:5465-5476.

More Related