Bone metabolism and osteoporosis in elderly patients treated with hormonal therapies for prostate cancer

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Bone metabolism and osteoporosis in elderly
patients treated with hormonal therapies for
prostate cancer
Susan F. Slovin, MD, PhD Genitourinary Oncology
Service Sidney Kimmel Center for Prostate and
Urologic Cancers Memorial Sloan-Kettering Cancer
Center New York, NY
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Egerdie B, Saad F. Can Urol Assoc J. 2010
Apr4(2)129-35
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Egerdie B, Saad F. Can Urol Assoc J. 2010
Apr4(2)129-35
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Androgen deprivation therapy (ADT) is
increasingly being prescribed for men with
prostate cancer
- Metastatic disease - Locally advanced or
high-risk non-metastatic - Recurrent disease
(biochemical recurrence) - Primary ADT The
number of prostate cancer survivors in the United
States is estimated at 2 million, and
approximately one-third of them are currently
receiving ADT.
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Prostate cancer and osteopenia/osteoporosis
Before ADT In a cross-sectional study, 45.2 of
ADT-naïve patients without metastatic disease had
osteopenia and 35.4 had osteoporosis. After
ADT Prevalence increased with duration of
treatment until after 10 years no patient on ADT
had a BMD within the normal range. BMD
generally decreases significantly at the spine
and hip, particularly during the first year of
ADT reported BMD losses after only 1 year of ADT
range up to 4.8 at the lumbar spine and 3.8 at
total hip.
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Prevalence of osteopenia and osteoporosis among
men with non-metastic prostate cancer effect of
ADT.
Morote J, et al. Urology 200769500
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Prostate cancer and fracture risk
The 5-year risk of vertebral and hip fractures is
2.2-fold higher in orchiectomized prostate cancer
patients than in controls. In one retrospective
study, a history of fracture since the diagnosis
of prostate cancer decreased median overall
survival from 160 months to 121 months (p 0.04)
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Prevalence of fractures in men with prostate
cancer
Shahinian et al. N Engl J Med. 2005352(2)154-64
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Osteoporosis and osteopenia are greatly
underdiagnosed and undertreated in men with
prostate cancer
Among 174 veterans with prostate cancer receiving
ADT, only 34 of those with nonmetastatic disease
had received any recommended screening,
prophylaxis, or therapy for osteoporosis, and
only 13 had received a dual-energy x-ray
absorptiometry (DXA) scan. Yee EF, et al. J Gen
Intern Med 2007221305-10.
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Impact of zoledronate on SREs in men with
prostate cancer
Saad F, et al. JNCI. 200294(19)1458-68
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Impact of zoledronate on bone turnover in men
with prostate cancer
Saad F, et al. JNCI. 200294(19)1458-68
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Annual Zoledronic Acid to Prevent GnRH
AgonistInduced Bone Loss in Men With Prostate
Cancer
serum N-telopeptide serum bone alkaline
phosphatase
Michaelson, et al. J Clin Oncol.
200725(9)1038-42
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Denosumab in men receiving androgen-deprivation
therapy for prostate cancer
Lumbar Spine Total Hip
Smith, et al. N Engl J Med. 2009361(8)745-55
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Denosumab in men receiving androgen-deprivation
therapy for prostate cancer
Smith, et al. N Engl J Med. 2009361(8)745-55
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Effects of denosumab on bone mineral density in
men receiving ADT for prostate cancer.
Smith, et al. J Urol. 2009 Dec182(6)2670-5
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Effects of denosumab on bone turnover
Fizazi et al. JCO 200927(10)1564-71
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Effects of denosumab on fracture risk
Fizazi et al. JCO 200927(10)1564-71
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Higano, Nature Clin Pract Urol, 2008
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Pain

• DJD

• Cancer-related

• Migratory
• Improves over time
• Responds to NSIADS
• Improves with activity
• Meds work as needed

• Stationary
• Unremitting
• Responds to NSAIDS
• Can inhibit activity
• May need to maintain schedule of regular
  analgesics

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Options

• Bone-seeking radiopharmaceuticals Quadramet
  (samarium-153)
• Radiotherapy
• Clinical trials Algeta (Radium)
• Bis phosphonates
• Physical therapy
• Combination analgesics

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Conclusions

• Androgen ablation impacts on bone health
• Early intervention important
• Role of exercise, bis phosphonates for health
  maintenance
• Novel agents to improve QOL and improve pain