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, nonmetastatic only disease 34% had of those received with 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

DJD

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

Pain

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