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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

Kurt Miller

Charité, Berlin


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Osteroporosis on the Rise* Maintaining Bone Health In Prostate Cancer Patients

Increase of osteroporotic fractures in Finnland

Incidence / 100 000

+192 %

* Kannus P, Osteoporos int 2000


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Prostate Cancer Bone Problems Maintaining Bone Health In Prostate Cancer Patients

  • Osteoporosis

  • Castration

  • Metastases


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Bone Density - Definitions Maintaining Bone Health In Prostate Cancer Patients

  • T-Score = Standard deviation from normal values

  • T-Score -1 bis – 2,5Osteopenia

  • T-Score < - 2,5Osteoporosis


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Bone Density - DXA Maintaining Bone Health In Prostate Cancer Patients


Risk factors for osteoporosis l.jpg
Risk Factors for Osteoporosis Maintaining Bone Health In Prostate Cancer Patients

  • 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.


Risk of osteoporosis after lhrh treatment l.jpg
Risk of Osteoporosis Maintaining Bone Health In Prostate Cancer Patientsafter 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.


Changes in bmd during gnrh agonist treatment 12 month data l.jpg
Changes in BMD During GnRH Agonist Treatment (12-Month Data) Maintaining Bone Health In Prostate Cancer Patients

P < .001

Lumbar spine

Total hip

Mittan D, et al. J Clin Endocrinol Metab. 2002;87:3656-3661.


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ADT Decreases BMD after 1 Year Maintaining Bone Health In Prostate Cancer Patients

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.


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Orchiectomy Maintaining Bone Health In Prostate Cancer Patients

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.


Risk of fracture after androgen deprivation for prostate cancer l.jpg
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.


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Risk of Fracture After Androgen Deprivation for Prostate Cancer

ReproducedwithpermissionfromShahinianVB,etal.NEnglJMed.2005;352:154-164.


Prostate cancer and bone loss l.jpg
Prostate Cancer and Bone Loss Cancer

  • 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


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Can We Prevent Bone Loss CancerResulting From ADT?


Classes of bisphosphonates l.jpg

O Cancer

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


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pamidronate Cancer

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.


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Oral Etidronate and CancerADT-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.


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Pamidronate in Patients with Prostate Cancer Receiving ADT Cancer

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.


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Pamidronate to Prevent CancerBone Loss During ADT

*P < .005.

Smith MR, et al. N Engl J Med. 2001;345:948-955.


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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.


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Effect of Zoledronic Acid on Lumbar Spine BMD at 1 Year ADT

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.


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P ADT < .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.


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Conclusions ADT

  • 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


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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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