Strategies for the prevention of treatment-related bone loss in women receiving adjuvant hormonal therapy.

More than 220,000 women will be diagnosed with breast cancer this year, and approximately 75% of these women will be long-term survivors of this disease. Survival has improved largely because of advances in adjuvant hormone therapy and chemotherapy, as well as early detection strategies. Because most women will receive adjuvant treatment, and the majority will survive cancer, it is increasingly important to understand the resultant toxicities and to devise monitoring and treatment strategies to avoid adverse long-term effects. Loss of bone mineral density leading to osteoporosis and increased risk of fracture as well as other morbidities is a well known complication of estrogen suppression associated with use of aromatase inhibitors (AIs) in postmenopausal women, and ovarian suppression with GnRH agonists or chemotherapy in premenopausal women. Hormone receptor positivity is increasingly frequent with increasing patient age, so that a large number of women already at risk for osteopenia associated with menopause are at risk for further bone loss caused by adjuvant hormone therapy with AIs. This article will review data on bone mineral density loss and risk of fracture in the large, randomized phase III trials comparing tamoxifen to AIs using the upfront, switching or extended hormone therapy approach. Data from prophylactic bisphosphonate intervention trials in both post- and premenopausal women will be discussed. Ongoing trials are described.