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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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slide1

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

Kurt Miller

Charité, Berlin

slide2

Osteroporosis on the Rise*

Increase of osteroporotic fractures in Finnland

Incidence / 100 000

+192 %

* Kannus P, Osteoporos int 2000

slide3

Prostate Cancer Bone Problems

  • Osteoporosis
  • Castration
  • Metastases
slide4

Bone Density - Definitions

  • T-Score = Standard deviation from normal values
  • T-Score -1 bis – 2,5Osteopenia
  • T-Score < - 2,5Osteoporosis
risk factors for osteoporosis
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.

risk of osteoporosis after lhrh treatment
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.

changes in bmd during gnrh agonist treatment 12 month data
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.

slide9

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.

androgen deprivation therapy increases fracture risk

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.

risk of fracture after androgen deprivation for prostate cancer
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.

slide12

Risk of Fracture After Androgen Deprivation for Prostate Cancer

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

prostate cancer and bone loss
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
classes of bisphosphonates

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

slide16

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.

oral etidronate and adt induced bone loss
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.

slide18

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.

slide19

Pamidronate to Prevent Bone Loss During ADT

*P < .005.

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

slide20

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.

slide21

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.

slide22

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.

conclusions
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
bmd should be assessed to treat osteoporosis and prevent fractures
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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