Androgen Ablation &Bone Metastasis

Androgen Ablation
Androgen deprivation therapy (ADT) is commonly used in the treatment of prostate cancer.53 Survival in men with nonmetastatic prostate cancer treated with ADT is long, with a median survival of greater than 7 years.54 Hence, long-term effects on bones are of particular concern. At least one study has also suggested skeletal fractures as an adverse predictor of overall survival in men with prostate cancer.55

Even at baseline, men with prostate cancer who have not received ADT have a higher incidence of osteoporosis than the general age-matched population.56 Effects of hormone treatment most likely compound the problem.21

A Danish case-control registry study compared more than 15,000 men aged older than 50 years who had fractures with 45,000 men who did not. The authors found that a diagnosis of prostate cancer was associated with an increased odds ratio (OR) for fracture of 1.8 (95% CI, 1.6-2.1) and ADT was associated with an increased OR of 1.7 (95% CI, 1.2-2.5). It was noted that the increased risk became apparent soon after diagnosis and persisted even in long-term survivors.57

Retrospective cohort studies of men who have survived prostate cancer for many years have demonstrated that ADT therapy is associated with an increase in fracture risk (Table 2).58-65 Shahinian et al performed a Surveillance, Epidemiology, and End Results (SEER) database study of 50,613 men who were diagnosed with prostate cancer between 1992 and 1997. Five years after starting treatment, 19.4% of survivors who received ADT developed a fracture at any site, whereas only 12.6% of survivors not receiving ADT developed a fracture.58 Dickman et al studied almost 18,000 men who were treated for prostate cancer with bilateral orchiectomy, and compared their fracture risk with that of approximately 360,000 healthy controls. The authors found that those who had undergone orchiectomy had a fracture risk over 10 years of 12% at the femoral neck alone, compared with 5% in the general population.60 Smith et al conducted a claims-based retrospective cohort study of 3887 men with nonmetastatic prostate cancer receiving GnRH agonists compared with 7774 who did not receive these agents. GnRH agonists were associated with an increased clinical fracture risk (7.88 clinical fractures per 100 person-years in the GnRH group vs 6.51 per 100 person-years in controls; relative risk [RR], 1.21; 95% CI, 1.14-1.29 [P < .001]).59 However, these studies are limited in that fractures were not designated as osteoporotic versus pathologic, and no relation with BMD was performed.