The Management of Bone Health in Prostate Cancer Rob Coleman Weston Park Hospital University of Shef

1
The Management of Bone Health in Prostate
CancerRob ColemanWeston Park
HospitalUniversity of Sheffield
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Osteoporosis in Prostate Cancer

• Duration of survival following diagnosis
  improving
• Earlier diagnosis
• Better treatments
• Increasing use of treatments inhibiting
  oestrogenic and androgenic beneficial effects on
  bone
• Possible direct effects of chemotherapy on
  skeletal health
• Effective interventions available

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Bone Remodeling
Marrow
Resorption
Reversal
Bone
Osteoclasts
Marrow
Formation
Quiescence
Bone
Osteoblasts
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Lifetime Changes in Bone Mass
BMD
Gain
Consolidation
Loss
Men
Women
Age
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Components of Bone Strength
Bone density
Bone quality

• Architecture
• Remodelling
• Accumulation of lesions (microfractures)
• Secondary mineralisation

aBMD g/cm2 vBMD g/cm3
NIH Consensus Development Panel. JAMA 2001 285
(6) 785-795
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What is Osteoporosis?

• A skeletal disorder characterized by compromised
  bone strength predisposing a person to an
  increased risk of fracture.

NIH Consensus Development Panel. JAMA 2001 285
(6) 785-795
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Osteoporotic Vertebral Fractures
Concave Wedge Crush
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Evaluation of Bone Mineral Density (BMD)

• DEXA of spine and hip is
• the gold standard
• Low energy X rays
• Relatively cheap
• Good QA of scanner and
• consistent operator essential
• Precision 2-3 between scans

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Typical BMD Result
Z score
T score
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Diagnosis of Osteoporosis
BMD T score
BMD young adult
Normal bone mass
-1.0
-1.0
Osteopenia
-2.5
-2.5
osteoporosis
Fracture Severe Osteoporosis
Adapted from Kanis, JA. Lancet 2002
359(9321)1929-36
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Risk of osteoporotic fracture

• 1SD decrease in BMD double the risk of fracture
  at this site (in women aged over 65).
• This relationship is strongest at the hip bone.

Relationship between BMD and relative risk of
fractures
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Endocrine Treatment Effects on Bone
Breast cancer
Prostate cancer

• Cytotoxic therapy
• - Aromatase inhibitors
• - GnRH agonists

• Cytotoxic therapy
• - Antiandrogens
• - GnRH agonists

Oestrogen depletion
Androgen depletion
BMD
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Bioavailable Oestradiol Concentrations
Aromatase Inhibitor Therapy
Adapted from Khosla et al. J Clin Endocrinol
Metab 2001863555-61
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CTIBL in Prostate Cancer

• A significant number of prostate cancer patients
  present with bone loss prior to androgen
  deprivation therapy
• Osteopenic patients given LHRH analogues are at
  significant risk of further bone loss
• BMD assessment during early months of treatment
  (baseline) and 12-24 months thereafter is
  recommended

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ADT Decreases BMD after 1 Year

• Change from
• Study N Treatment baseline BMD
• Eriksson et al1 11 Orchiectomy Hip
  -9.6 Radius -4.5
• Maillefert et al2 12 GnRH agonist Hip
  -3.9 L spine -4.6
• Daniell et al3 26 Orchiectomy or Hip -2.4
  GnRH agonist
• Berruti et al4 35 GnRH agonist Hip
  -0.6 L spine -2.3

ADT
1 Eriksson S, et al. Calcif Tissue Int. 1995
5797-99. 2 Maillefert JF, et al. J Urol.
19991611219-1222. 3 Daniell HW, et al. J
Urol. 2000163181-186. 4 Berruti A, et al. J
Urol. 20021672361-2367.
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Risk of Osteoporosis after LHRH Treatment
Plt0.001
In men osteopenic at baseline
Plt0.001
Weston R, Hussain A, Stephenson RN, George E,
Parr NJ. Presented at the British Association of
Urological Surgeons Annual Meeting June 23-27,
2003, in Manchester, UK.
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Fractures During GnRH Agonist Treatment
Shahinian et al (2005) NEJM 352154-164
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Pamidronate to Prevent Bone Loss During ADT
Plt0.005 for each comparison
N47
AP Spine
Total Hip
Smith et al (2001) NEJM 345948-955
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Zoledronic Acid Prevents Bone Loss During ADT
Plt0.001 for each comparison
N106
Lumbar spine
Total hip
Smith M et al (2003) Urology
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Clinical Scenario

• 73 year old generally fit man presents with
  locally advanced prostate cancer
• No risk factors for osteoporosis
• Radiotherapy to prostate
• Commenced on 3 monthly LHRH analogue
• Good biochemical remission
• DEXA scan performed
• Spine T score -1.4
• Hip T score -2.0

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Management Options

• Repeat BMD measurement in 12-18 months
• Commence calcium and vitamin D supplements
• Lifestyle advice
• Commence prophylactic oral bisphosphonate
• Commence prophylactic iv bisphosphonate
• Do nothing
• Other

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Management Options

• Repeat BMD measurement in 12-18 months
• Commence calcium and vitamin D supplements
• Lifestyle advice
• Commence prophylactic oral bisphosphonate
• Commence prophylactic iv bisphosphonate
• Do nothing
• Other

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Subsequent Progress

• Remained in biochemical remission
• Started walking 3-4 miles twice a week
• Took Calcichew D3 Forte daily
• BMD 18 months later showed annual loss of
• 6 at spine (T-2.3) and
• 5 at hip (T -2.8)
• Urinary NTX elevated at 120nmol/mmol creatinine

Subsequent management ?
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Management Options

• Continue current treatment and repeat BMD
  measurement in 12 months
• Commence prophylactic oral bisphosphonate
• Commence prophylactic iv bisphosphonate
• Commence low dose oestrogen
• Do nothing
• Other

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Management Options

• Continue current treatment and repeat BMD
  measurement in 12 months
• Commence prophylactic oral bisphosphonate
• Commence prophylactic iv bisphosphonate
• Commence low dose oestrogen
• Do nothing
• Other

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Subsequent Progress

• Started zoledronic acid 4mg iv every 6 months
• Continued Calcichew and exercise
• 3 months later NTX normal at 35nmol/mmol
  creatinine
• 12 months later BMD had improved by
• 7 at spine and
• 4 at hip

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Conclusions

• Cancer treatment induced bone loss (CTIBL) an
  increasingly important consequence of therapy
• CTIBL more rapid with ADT use
• National guidance on management required
• Effective prevention of CTIBL posssible with
  bisphosphonates