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Purpose: The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer. However, its use is associated with accelerated bone loss and an increase in fracture risk. The ARIBON trial is a double-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking anastrozole., Experimental Design: BMD was assessed in 131 postmenopausal, surgically treated women with early breast cancer at two U.K. centers. Of these, 50 patients had osteopenia (T score -1.0 to -2.5) at either the hip or lumbar spine. All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation. In addition, osteopenic patients were randomized to receive either treatment with ibandronate 150 mg orally every month or placebo., Results: After 2 years, osteopenic patients treated with ibandronate gained +2.98% (range -8.9, +19.9) and +0.60% (range -9.0, +6.9) at the lumbar spine and hip, respectively. Patients treated with placebo, however, lost -3.22% (range -16.0, +4.3) at the lumbar spine and -3.90% (range -12.3, +7.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (P < 0.01). At 12 months, urinary n-telopeptide, serum c-telopeptide, and serum bone-specific alkaline phosphatase levels declined in patients receiving ibandronate (30.9%, 26.3%, and 22.8%, respectively) and increased in those taking placebo (40.3%, 34.9%, and 37.0%, respectively)., Conclusions: Monthly oral ibandronate improves bone density and normalizes bone turnover in patients treated with anastrozole.

Purpose: Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment-induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration., Experimental Design: Sixty-six patients who were osteopenic at >1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay., Results: The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively (P < 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was approximately 58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively (P < 0.001)., Conclusions: A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption. Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.

Despite an increasing incidence, the outlook for women with early breast cancer has improved considerably over recent years with a steady fall in the death rate in most western countries. This is due, at least in part, to the widespread use of adjuvant systemic therapy. However, some of these treatments have adverse effects on bone metabolism with increased bone loss which may result in osteoporosis and associated fractures. Most of the effects on bone are mediated by endocrine changes, either induction of an early menopause by chemotherapy and ovarian ablation, or further suppression of postmenopausal circulating oestrogens by aromatase inhibitors. There may also be direct effects of chemotherapy on bone cell function. The pathophysiology of osteoporosis in breast cancer patients, the methods of assessment and treatment options are reviewed. Bone health is a highly topical issue in breast cancer with the emergence of data supporting the use of several years of treatment with aromatase inhibitors. Guidelines on who and how to screen for bone loss, and simple, safe strategies for treatment to prevent osteoporosis are presented.

Bisphosphonates will become increasingly important in the management of patients with breast cancer. Currently, bisphosphonates are used to treat bone metastasis because they effectively relieve pain, prevent pathological fractures and treat hypercalcaemia of malignancy. Recent advances in systemic adjuvant therapies for breast cancer are improving survival but many treatments are detrimental to bone and can increase the risk of fracture. The monitoring of breast cancer patients at risk of developing osteoporosis will become increasingly important as survival times improve and more potent treatments are developed. Bisphosphonates may also play a role as an adjuvant therapy for the prevention of bone metastasis in high-risk breast cancer patients.