Bone metastasis prevention with bisphosphonates Bisphosphonate prevention of bone metastasis is a very promising area of research at present. In a study presented at the 2004 ASCO Annual Meeting, 1079 patients with primary operable breast cancer were randomized to receive bisphosphonates or placebo for 2 years on top of standard adjuvant therapy. The results showed that there were significantly fewer cases of first bone metastases in the bisphosphonate group than in the placebo group at 2 years (P=0.016) and, more importantly, there were significantly fewer deaths in the bisphosphonate group than in the placebo group at 10 years of follow-up (P=0.048). Studies of Zeta as an adjuvant treatment for breast cancer to prevent bone metastasis are forthcoming, with two studies enrolling 6,000 and 3,300 cases, respectively. Li Dequan, Department of Breast Surgery, Cancer Hospital, Guangxi Medical University Bisphosphonates – clodronate, pamidronate and zoledronic acid are all effective in the treatment of metastatic bone disease caused by breast cancer and multiple myeloma. To date, zoledronic acid is the only bisphosphonate proven effective in treating prostate cancer, renal cell carcinoma, and other solid tumors in randomized controlled studies. It can reduce and delay the occurrence of bone complications, thereby improving patients’ quality of life and reducing the cost of palliative care. In addition to reducing SRE caused by bone metastases, zoledronic acid can prevent bone invasion at the primary site of the tumor. Therefore, zoledronic acid needs to be given in the early adjuvant phase of tumor treatment, but the ideal dose and treatment regimen need further investigation. Several large clinical studies are currently underway or planned to investigate the prevention of bone metastases with zoledronic acid, the prevention of tumor treatment-induced bone loss, and the exploratory use of zoledronic acid. Prevention of Bone Metastases The purpose of the AZURE study is to explore the effectiveness of adjuvant zoledronic acid in reducing recurrence in patients at high risk for stage II/III localized breast cancer. The expected duration of the study is 60 months and 3,300 patients are expected to be enrolled and subsequently randomized to receive standard therapy combined with zoledronic acid or placebo and observed for time to development of bone metastases and disease-free survival. To date, more than 1,200 patients have been enrolled, and preliminary results will be published in 2008. Another study conducted by the U.S. SWOG Study Group, which included 6,000 patients, compared disease-free survival rates for adjuvant treatment of primary breast cancer with zoledronic acid, clodronate, and ibandronate, with enrollment ending in 2009. Prevention of Cancer Therapy-Induced Bone Loss Preliminary results from the ongoing ABCSG-12 study showed that zoledronic acid was effective in preventing CTIBL in premenopausal breast cancer patients receiving endocrine therapy. the results suggest that the use of zoledronic acid to prevent cancer therapy-induced bone loss is feasible. Patients at high risk of bone loss (including those treated with long-term aromatase inhibitors) should have their BMD measured annually and should receive zoledronic acid for T values below -2.5 and calcium and vitamin D supplementation for T values between -1.5 and -2.5. The Z-FAST and ZO-FAST studies will answer the question of whether prophylactic application of bisphosphonates is preferable to therapeutic application. early data from the Z-FAST study showed that The CALGB 79809 study will evaluate the efficacy of daily calcium and vitamin D supplementation in combination with zoledronic acid once every 3 months in patients with stage I-III premenopausal breast cancer with ovarian failure due to adjuvant chemotherapy. In conclusion, the potential therapeutic role of bisphosphonates far exceeds their initial indications (malignant hypercalcemia and cancer-induced bone loss). Current evidence suggests that zoledronic acid is an effective bisphosphonate for the treatment of bone metastases and is the only bisphosphonate proven to be effective in solid tumors other than breast cancer; in addition, zoledronic acid is effective in preventing CTIBL, and a series of large ongoing studies will evaluate the efficacy of zoledronic acid in preventing bone metastases.