Impact of aromatase inhibitors on bone health in breast cancer patients

Following the implementation of the third generation aromatase inhibitors in the treatment algorithms for early breast cancer, special attention has been given to the influence of these drugs on bone health. Due to their potent estrogen suppression, the aromatase inhibitors anastrozole and letrozole, as well as the aromatase inactivator exemestane, enhance bone loss in postmenopausal women reflected in decreasing levels of bone mineral density. Moreover, all major phase III trials involving aromatase inhibitors in the adjuvant setting have reported increased fracture rates. All in all, there is no hard evidence to suggest major differences between the individual compounds concerning their side-effects on bone. The consequences of AI therapy on bone are in addition modified by a variety of factors like the BMD level prior to therapy, time since menopause, and vitamin D status. Strategies to avoid bone loss during AI therapy have shown promising results. Thus, bisphosphonates have been shown to prohibit bone loss during AI therapy if used upfront. Novel treatment strategies, like antibodies against RANKL have been developed and promising preliminary results have been published from early trials. Standardized guidelines to avoid or minimize bone loss during AI therapy have been developed, in most countries involving calcium and vitamin D supplementation, as well as BMD measurements to identify patient subgroups demanding bisphosphonate therapy.