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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
Egerdie B, Saad F. Can Urol Assoc J. 2010 Apr;4(2):129-35
Egerdie B, Saad F. Can Urol Assoc J. 2010 Apr;4(2):129-35
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.
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.
Prevalence of osteopenia and osteoporosis among men
with non-metastic prostate cancer: effect of ADT.
Morote J, et al. Urology 2007;69:500
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)
Prevalence of fractures in men with prostate cancer
Shahinian et al. N Engl J Med. 2005;352(2):154-64
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 2007;22:1305-10.
Impact of zoledronate on SREs in men with prostate cancer
Saad F, et al. JNCI. 2002;94(19):1458-68
Impact of zoledronate on bone turnover in men with
prostate cancer
Saad F, et al. JNCI. 2002;94(19):1458-68
Annual Zoledronic Acid to Prevent GnRH Agonist–
Induced Bone Loss in Men With Prostate Cancer
serum N-telopeptide
serum bone alkaline phosphatase
Michaelson, et al. J Clin Oncol. 2007;25(9):1038-42
Denosumab in men receiving androgen-deprivation
therapy for prostate cancer
Lumbar Spine
Total Hip
Smith, et al. N Engl J Med. 2009;361(8):745-55
Denosumab in men receiving androgen-deprivation
therapy for prostate cancer
Smith, et al. N Engl J Med. 2009;361(8):745-55
Effects of denosumab on bone mineral density in men
receiving ADT for prostate cancer.
Smith, et al. J Urol. 2009 Dec;182(6):2670-5
Effects of denosumab on bone turnover
Fizazi et al. JCO 2009;27(10):1564-71
Effects of denosumab on fracture risk
Fizazi et al. JCO 2009;27(10):1564-71
Higano, Nature Clin Pract Urol, 2008
Pain
DJD
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Migratory
Improves over time
Responds to NSIADS
Improves with activity
Meds work as needed
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Cancer-related
Stationary
Unremitting
Responds to NSAIDS
Can inhibit activity
May need to maintain
schedule of regular
analgesics
Options
• Bone-seeking radiopharmaceuticals:
Quadramet (samarium-153)
• Radiotherapy
• Clinical trials: Algeta (Radium)
• Bis phosphonates
• Physical therapy
• Combination analgesics
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