Managing bone loss and bone metastases in prostate cancer patients: a focus on bisphosphonate therapy.

Androgen deprivation therapy (ADT) and bone metastases are the most important risk factors for developing skeletal complications (eg, bone loss, pathologic fractures) in prostate cancer (PC) patients with locally advanced and metastatic disease. Bisphosphonates, which inhibit excessive osteoclast activity caused by ADT and bone metastases, have proven to be safe and effective in preventing skeletal complications and presently are the standard of care in patients with metastatic disease. Bisphosphonates should be considered for use in all PC patients with locally advanced disease initiating ADT for an intended duration of at least 1 year, especially those with a low baseline bone mineral density.

Managing bone loss in men with locally advanced prostate cancer receiving androgen deprivation therapy.

PURPOSE: We reviewed the pathogenesis, diagnosis, prevalence, prevention and treatment of bone loss in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy. MATERIALS AND METHODS: Using PubMed we performed a comprehensive literature search to identify articles on bone mineral density loss in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy. Pertinent articles were reviewed and evaluated. RESULTS: Bone mineral density loss and related fractures were recently established as significant adverse events associated with androgen deprivation therapy. Patients with nonmetastatic prostate cancer receiving androgen deprivation therapy experience annual bone mineral density losses of 0.6% to 4.6% with the most significant loss within year 1 of therapy. In addition to calcium and vitamin D supplements, current treatment options for androgen deprivation therapy induced bone loss include synthetic estrogens, selective estrogen receptor modulators and bisphosphonates. Recent safety concerns have been identified, including renal dysfunction with intravenous bisphosphonates and osteonecrosis of the jaw with oral and intravenous bisphosphonates. However, minimal renal dysfunction and no cases of osteonecrosis of the jaw have been reported in this setting. CONCLUSIONS: Because the most significant bone mineral density loss occurs within year 1 of androgen deprivation therapy and most fractures in healthy men occur in those without osteoporosis, early intervention is warranted to prevent skeletal morbidity in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy. Although the majority of and the most compelling evidence supports the use of bisphosphonates for preventing and treating androgen deprivation therapy induced bone loss, further study is needed to define the optimal regimen, timing of initiation and duration of therapy as well as long-term efficacy and safety.

The effect of zoledronic acid on bone mineral density in patients undergoing androgen deprivation therapy.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of zoledronic acid compared with placebo in preventing bone mineral density (BMD) loss and suppressing bone markers when initiated during the first year of androgen deprivation therapy in patients with locally advanced prostate cancer. PATIENTS AND METHODS: Patients were randomized to receive zoledronic acid 4 mg or placebo intravenously every 3 months. Lumbar spine (LS) and total hip BMD was measured using dual-energy x-ray absorptiometry at baseline and at week 52. N-telopeptide (NTX) and bone-specific alkaline phosphatase (BSAP) were evaluated at baseline and every 12 weeks. Safety assessments were performed throughout the study. RESULTS: Efficacy analyses included 106 patients and 109 patients in the zoledronic acid and placebo groups, respectively. At week 52, the least squares mean BMD percentage differences were 6.7% for LS and 3.7% for total hip (P < 0.0001 for both). In the zoledronic acid group, decreases in NTX ((-)14% to (-)28%) and BSAP ((-)31% to (-)37%) levels were significant and sustained; changes in NTX levels and LS BMD (r = (-)0.25; P = 0.04) and in BSAP levels and hip BMD (r = (-)0.28; P = 0.02) were significantly correlated. Only traumatic fractures were reported for 2 and 3 patients receiving zoledronic acid and placebo, respectively. One patient in each group experienced acute renal failure. Osteonecrosis of the jaw was not reported. CONCLUSION: Zoledronic acid (4 mg intravenously every 3 months) was safe and effective in preventing bone loss and reducing bone turnover in patients with prostate cancer when initiated during the first year of androgen deprivation therapy; patients with low baseline BMD experienced the greatest benefit.