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Table 2: Pharmaceutical Interventions for the Prevention of Bone Loss in Men with Prostate Cancer and No Bone Metastases Receiving
Conventional Androgen-deprivation Therapy
Mean Percentage Change in BMD
Drug Anti-bone-loss Therapy Lumbar Spine Total Hip Femoral Neck Reference(s)
Alendronate 70mg/wk PO 1 year 3.7 0.7 1.6 Greenspan, 2007,
versus Greenspan, 2008
placebo -1.4 -0.7 -0.7
(p<0.001) (p=0.002) (p<0.001)
Risedronate 6 months 4.9% NR No change Ishizaka, 2007
Pamidronate 60mg IV q 12 weeks 48 weeks No change No change No change Smith, 2001
control group -3.3 -1.8 No change
(p<0.001) (p=0.005) (p=0.56)
Zoledronic acid 4mg IV q 3 months 48 weeks–1 year 4.6–5.6 1.1–1.6 1.2–1.3 (NR in Israeli) Smith, 2003,
versus Ryan, 2006,
placebo -2.2 to -2.0 -2.8 to -2.1 -2.4 to -2.1 Isreali, 2007
(p<0.001) (p<0.001) (p<0.001)
Zoledronic acid 4mg IV x 1 dose 1 year 4 0.7 2 Michaelson, 2007
placebo -3.1 -1.9 -0.1
(p<0.001) (p=0.004) (p=0.06)
1 year NR NR -1.2% Eriksson, 1995
orchiectomy NR NR -9.6%
Raloxifene 60mg/day PO 1 year 1 1.1 0.3 Smith, 2004
control group -1 -2.6 -1.7
(p=0.07) (p<0.001) (p=0.06)
Toremifene 80mg/day PO 1 year 1.6 0.7 0.2 Smith, 2008
placebo -0.7 -1.3 -1.3
(p<0.001) (p=0.001) (p=0.009)
ADT = androgen-deprivation therapy, BMD = bone mineral density; NR = not reported. a = ADT consisted of GnRH agonist, GnRH agonist ± antiandrogen, estrogen, or orchiectomy; b = BMD
measured by dual-energy X-ray absorptiometry; c = p value provided for between-group comparison; d = polyestradiol phosphate 160mg intramuscularly q four weeks x three months then 80mg q
four weeks thereafter and ethinyl estradiol 1mg per oral (po) once-daily (qd) x two weeks followed by 0.15mg po qd either concomitantly or after three months of polyestradiol phosphate
appear to play a larger role in the AEs of ADT than testosterone conventional modalities may have less of a negative impact on BMD, and
Estrogen deficiencies cause osteoclast activation, decrease some may actually prevent bone loss (see Table 1).
osteoclast apoptosis, and possibly decrease osteoblast formation, Scherr and colleagues
found that markers of bone resorption
proliferation, and function.
Ultimately, the net result of this imbalance (N-telopeptide [NTX]) did not increase from baseline in prostate cancer
is bone loss. Although the greatest degree of bone loss tends to occur patients receiving diethylstilbesterol (DES) monotherapy compared with
during the first year of ADT, the prevalence of osteopenia/osteoporosis controls; in contrast, NTX levels increased in men who had undergone an
appears to increase with prolonged duration of ADT.
Results of one orchiectomy or were receiving GnRH monotherapy. Similarly, in another
study found that after only two years of GnRH agonist (± bicalutamide) study evaluating the bone effects of antiandrogen (bicalutamide)
therapy, approximately 40% of bone-metastases-free prostate cancer monotherapy, NTX and deoxypyridinoline (biochemical markers of
patients developed osteoporosis; this rate doubled to approximately 80% osteoclast activity) levels were significantly higher in men receiving a
after 10 years of therapy, and no patients had a normal BMD beyond GnRH agonist compared with patients receiving bicalutamide
Fracture risk also appears to increase with the duration of monotherapy.
Bone turnover marker levels were similar between the
ADT; however, studies evaluating the long-term incidence in patients hormone-naïve and bicalutamide groups.
These results suggest that
without bone metastases are needed.
antiandrogen monotherapy may prevent bone loss in men requiring
long-term ADT, likely as a result of uninhibited estrogen activity. Larger
Little is known about the extent to which other forms of ADT such as studies to confirm these results are needed. BMD loss may also be
estrogen and antiandrogen monotherapy, intermittent GnRH agonists minimized with intermittent GnRH agonist therapy, allowing for BMD
(± antiandrogen), GnRH antagonists, and ketoconazole affect bone stabilization to occur during the off-treatment period, although the
health. However, results of studies indicate that some of the less long-term effects of intermittent ADT on BMD are unknown.
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