1. Preventing Osteoporotic Fractures
in Men With Early-Stage Prostate
Cancer
Michael A. Carducci, MD
AEGON Professor in Prostate Cancer
Research
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland
This program is supported by an educational donation from

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Disclosure
Michael A. Carducci, MD, has disclosed that he has
received consulting fees from Amgen, Bristol-Myers Squibb,
and Novartis.

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Case 1
 68-yr-old retired truck driver
 High blood pressure; diabetes, noninsulin requiring
 BMI: 32 (obese); nonsmoker; alcohol intake: 2-3 beers/day
 Presents with PSA 50
 DRE clinical stage T3b
 TRUS: biopsies with Gleason 4 + 3 in 9 of 12 cores
 No detectable metastases by bone scan and CT
 After discussing options, patient decides on external beam
radiation therapy + 3 yrs of ADT

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Would you recommend additional therapy
to prevent bone loss/fractures?
A. No, since I did not get a baseline BMD
B. Yes, regardless of baseline BMD
C. Yes, but only if he is osteoporotic
D. Yes, if he is osteopenic or osteoporotic

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ADT-Associated Bone Loss
Healthy men[1] 0.5%
Late menopausal women[1] 1.0%
Early menopausal women[1] 2.0%
AI therapy in postmenopausal women[2] 2.6%
Bone marrow transplant[3] 3.3%
Androgen deprivation therapy[4] 4.6%
AI therapy + GnRH agonist[5] 7.0%
Ovarian failure 7.7%
secondary to chemotherapy[6]
0 2 4 6 8
Lumbar Spine BMD Loss at 1 Yr (%)
1. Kanis JA. Osteoporosis. Blackwell Healthcare Communications Ltd; 1997. 2. Eastell R, et al. J Bone
Mineral Res. 2002;17(suppl 2). Abstract 1170. 3. Lee WY, et al. J Clin Endocrinol Metab. 2002;87:329-
335. 4. Maillefert JF, et al. J Urol. 1999;161:1219-1222. 5. Gnant M. Breast Cancer Res Treat. 2002;
76(suppl 1):S31. Abstract 12. 6. Shapiro CL, et al. J Clin Oncol. 2001;19:3306-3311.

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Proportion of Patients With Fractures
1-5 Yrs After Cancer Diagnosis
+6.8%; P < .001
21 No ADT (n = 20,035)
ADT (n = 6650)
18
19.4
15
Frequency (%)
12 12.6
9
+2.8%; P < .001
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.

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Fractures Impact Mortality and Life
Expectancy
 Hip fracture
– Affects life expectancy dramatically[1,2]
– Aged 60-69 yrs: 11.5 yrs of decreased life expectancy
– Aged 0-79 yrs: 5.0 yrs of decreased life expectancy
 Vertebral facture
– Prevalence in men is high (20%)[3]
– Clinical consequences: pain, kyphosis, loss of height, respiratory problems [4,5]
– 4 x increased risk of subsequent fracture[6]
– Predict increased mortality in men with a 10-yr HR of 2.4
(95% CI: 1.6-3.9)[6,7]
1. Cree M, et al. J Am Geriatr Soc. 2000;48:283-288. 2. Center JR, et al. Lancet. 1999;353:878-882. 3. O’Neill TW, et al. J
Bone Miner Res. 1996;11:1010-1018. 4. Matthis C, et al. Osteoporosis Int. 1998;8: 364-372. 5. Francis RM, et al. QJM.
2004;97:63-74. 6. Johnell O, et al. Osteoporos Int. 2004;15:175-179. 7. Lau E, et al. J Bone Joint Surg Am. 2008;90:1479-
1486. 8. Hasserius R, et al. Osteoporos Int. 2003;14:61-68.

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Screening for Bone Loss in Men:
Who Is at Risk?
Demographic Factors 65 yrs of age or older
History Family history of osteoporotic fracture
Fragility fracture after 40 yrs of age
Significant height loss
Lifestyle and Dietary Factors Smoking
Excessive intake of alcohol or caffeine (> 4 cups/day)
Inadequate dietary calcium intake
Weight < 57 kg (or loss of > 10% of weight at 25 yrs of age)
Physical Findings Vertebral deformity (eg, kyphosis) or osteopenia evident on x-ray
Diseases Associated With Bone Loss Prostate cancer
COPD
Malabsorption syndrome
Hyperparathyroidism
Hyperthyroidism
Hypogonadism
Rheumatoid arthritis
Renal insufficiency
Vitamin D deficiency
Treatments Associated With Bone Loss ADT
Anticonvulsants
Heparin
Systemic glucocorticoids (duration > 3 mos)
Entries in bold are considered major risk factors.
Brown JP, et al. CMAJ. 2002;167:S1-S34. Greenspan SL. J Clin Endocrinol Metab. 2008;93:2-7.

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The FRAX® Index: Assessing Fracture Risk
Available at: http://www.sheffield.ac.uk/FRAX/. Image used with permission of the WHO Collaborating
Centre for Metabolic Bone Diseases, University of Sheffield. FRAX ® is registered to Professor JA Kanis,
University of Sheffield.

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Case 2
 80-yr-old male with biochemically recurrent, nonmetastatic
prostate cancer starting ADT for a PSA of 15
 5′9″ (175.3 cm), 158 lbs (72.1 kg)
 DEXA scan at baseline reveals T-score of -0.9 at the
femoral neck of the left hip and -0.2 at the spine
 Patient also has Crohn’s disease and frequently receives
steroid treatment
 Drinks 4 glasses of wine/day and is a 60 pack-yr cigarette
smoker
 No previous history of fracture

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In addition to lifestyle modification, would
you also recommend bone-targeted
therapy for this patient?
A. No
B. Yes, alendronate 70 mg/wk PO
C. Yes, denosumab 60 mg SC q6m
D. Yes, zoledronic acid 5 mg IV annually
E. Yes, zoledronic acid 4 mg IV annually
F. Yes, zoledronic acid 4 mg IV quarterly

13. Treatment Options

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Alendronate Increases BMD During
GnRH Agonist Therapy
5 12-Mo Data
4
BMD Percent Change
3
Placebo
2 Alendronate
1
0
-1
-2
-3
Lumbar Total
Spine Hip
Greenspan SL, et al. Ann Intern Med. 2007;146:416-424.

15. Maximizing Skeletal Integrity in Patients With Cancer
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Annual Zoledronic Acid Increases BMD
During GnRH Agonist Therapy
6 Final 12-Mo Data
P < .005 for each comparison
4
BMD Percent Change
2 Placebo
Zoledronic acid 4 mg/yr IV
0
-2
-4
-6
Lumbar Total
Spine Hip
Michaelson MD, et al. J Clin Oncol. 2007;25:1038-1042.

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Quarterly Zoledronic Acid Increases BMD
During GnRH Agonist Therapy
8 Final 12-Mo Data
P < .001 for each comparison
6
BMD Percent Change
4 Placebo
Zoledronic acid
2
0
-2
-4
Lumbar Total
Spine Hip
Smith MR, et al. J Urol. 2003;169:2008-2012.

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Denosumab Increased BMD at All Skeletal
Sites
10 A. Lumbar Spine 10 B. Total Hip
8 8
From Baseline (%)
From Baseline (%)
Change in BMD
Change in BMD
6 Denosumab 6
4 4 Denosumab
Difference at 24 mos,
2 6.7 percentage points 2 Difference at 24 mos,
0 0 4.8 percentage points
-2 Placebo -2
-4 -4 Placebo
-6 -6
01 3 6 12 24 36 01 3 6 12 24 36
Mos Mos
10 C. Femoral Neck 10 D. Distal Third of Radius
8 8
From Baseline (%)
From Baseline (%)
Change in BMD
Change in BMD
6 6
4 Denosumab 4
Denosumab
2 Difference at 24 mos,
2
0 3.9 percentage points 0 Difference at 24 mos,
5.5 percentage points
-2 -2
Placebo Placebo
-4 -4
-6 -6
01 3 6 12 24 36 01 3 6 12 24 36
Mos Mos
Smith MR, et al. N Engl J Med. 2009;361:745-755.

18. Maximizing Skeletal Integrity in Patients With Cancer
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Denosumab for Fracture Prevention
10 Denosumab
Placebo
New Vertebral Fracture (%)
8
P = .004 P = .004 P = .006
6
3.9
4 3.3
1.9
2 1.5
1.0
0.3
0
12 24 36
Patients Mos
at Risk, n 13 2 22 7 26 10
Smith MR, et al. N Engl J Med. 2009;361:745-755.

19. Maximizing Skeletal Integrity in Patients With Cancer
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Conclusions
 Osteoporosis and fractures are an important health
problem in older men
 ADT for prostate cancer increases risks for osteoporosis
and fractures
 Some but not all men require drug therapy to prevent
fractures during ADT
 Effective therapies are available
– Bisphosphonates increase BMD
– Denosumab increases BMD and decreases vertebral
fractures

20. Go Online for More Education
on Bone Health
Interactive Decision Support Tools: Experts make treatment
recommendations for patients with prostate or breast cancer
Optimizing Bone Health in Patients With Cancer: Proceedings of an
Independent Expert Panel
Downloadable slides
clinicaloptions.com/oncology