Frequency of zoledronic acid to prevent further bone loss in osteoporotic patients undergoing androgen deprivation therapy for prostate cancer

OBJECTIVE To evaluate the efficacy of zoledronic acid (ZA) in osteoporotic patients with prostate cancer receiving either luteinizing hormone-releasing hormone agonists (LHRHA, which accelerate bone loss) or bicalutamide (which preserves bone mineral density, BMD) as androgen-deprivation therapy is the mainstay of treatment for advanced prostate cancer, and many patients are osteoporotic at presentation, with others becoming so on treatment. PATIENTS AND METHODS Fifty-eight osteoporotic men with non-metastatic prostate cancer were followed for 3 years. Patients were randomly assigned to receive either LHRHA (29) or bicalutamide (29). All received 4 mg ZA 3-monthly for 1 year. BMD was measured by dual energy X-ray absorptiometry at four times: 1 year before ZA; immediately before ZA; after five infusions; and 1 year afterwards. Bone turnover markers (BTMs) were measured at 3-monthly intervals on ZA and 1 year later. All patients had radiography of the thoracolumbar spine at baseline and after ZA. RESULTS Patients on LHRHA showed a 4.9% decrease in BMD before ZA, a 1.6% increase after ZA and a 3.0% decrease 1 year later, compared to 2.0% increase, 7.8% increase and 1.9% decrease, respectively, in those on bicalutamide. BTMs decreased significantly after ZA. Seven patients (12%) had vertebral fractures at baseline, with none deteriorating at 1 year; two (3.5%) developed mandibular osteonecrosis. CONCLUSION Before ZA, BMD decreased on LHRHA, but was maintained on bicalutamide. Treatment with 3-monthly ZA increased BMD and suppressed BTMs in osteoporotic patients both on LHRHA and bicalutamide, but to a greater extent in the latter. However, 1 year after the last infusion, BMD declined, suggesting that annual administration is inadequate in these patients. The optimum frequency might be related to BMD at time of bisphosphonate initiation.