Long‐term changes in bone mineral density and predicted fracture risk in patients receiving androgen‐deprivation therapy for prostate cancer, with stratification of treatment based on presenting values

Abstract

To study the long-term effects of androgen-deprivation therapy (ADT) using luteinizing hormone-releasing hormone (LHRH) agonists or antiandrogen therapy with bicalutamide on bone mineral density (BMD) of selected groups of patients with newly diagnosed advanced prostate cancer, stratified by BMD at presentation and to predict alterations in fracture risk. In all, 618 men with a mean (sd, range) age of 73 (7.1, 49-94) years, initiating ADT for prostate cancer were prospectively recruited and followed from October 1999 to January 2007. BMD was measured by forearm dual-energy X-ray absorptiometry (DEXA) before ADT and repeated annually. Patients with osteoporosis (T-score < or =-2.5) were commenced on bicalutamide; patients with osteopenia (T-score between -1.0 and -2.5) and normal BMD (T-score > -1.0) were commenced on an LHRH agonist. Patients with osteopenia and osteoporosis received calcium and vitamin D supplements. Over 7 years, 1690 DEXA scans were performed. In all, 41% of patients with newly diagnosed prostate cancer were osteoporotic, 39% were osteopenic and 20% had normal BMD. In the normal group, treated with an LHRH agonist, there were significant decreases in BMD (1 year 1.2%; 2 year 3.7%; 3 year 6.5%; 4 year 8.9%; 5 year 9.9%; 6 year 12.7%), which also occurred in the patients with osteopenia with 60% developing osteoporosis after 2 years (1 year 1.8%; 2 year 5.1%; 3 year 8.0%; 4 year 8.2%; 5 year 11.5%; 6 year 14.1%). By contrast, the osteoporotic group maintained BMD (1 year 0.5%; 2 year 0%; 3 year +1.2%; 4 year 0.5%; 5 year 1.7%; 6 year 2.2%). Patients treated with an LHRH agonist have significant and sustained decreases in BMD, whereas bicalutamide maintains BMD. We advocate routine assessment of BMD before ADT, with surveillance thereafter.