Aromatase Inhibitor-Associated Bone Loss
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Aromatase Inhibitor-Associated Bone Loss Clinical Considerations Shubham Pant and Charles L. Shapiro The Comprehensive Breast Health Services, Arthur G. James Cancer Hospital and Richard J. Solve Research Institute, The Ohio State University Medical Center, Columbus, Ohio, USA
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2591 1. Mechanisms of Bone Loss and Estrogen Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2592 2. Aromatase Inhibitors (AIs) Cause Estrogen Deficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2592 3. AIs Increase Fracture Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2593 4. AI Effects on Bone Mineral Density and Fracture Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2594 5. Monitoring and Prevention of AI-Induced Bone Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2595 6. Bisphosphonates and Other Treatments to Prevent AI-Induced Bone Loss . . . . . . . . . . . . . . . . . . . . . 2596 7. Summary and Key Points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2597
Abstract
Aromatase inhibitors (AIs) are standard treatments for postmenopausal women with estrogen responsive breast cancers. The mechanism of AIs, inhibition of the aromatase enzyme that causes decreases in endogenous estrogens, is responsible for bone loss and increased fractures. Screening and prevention of AI-induced bone loss closely follows the standard recommendations for postmenopausal osteoporosis. Lifestyle changes such as increasing physical activity and weightbearing exercise, stopping smoking, and taking adequate amounts of daily calcium and vitamin D promote bone and overall health. Bisphosphonates are specific inhibitors of osteoclasts and reduce bone loss in women treated with AIs. The optimal dose administration schedule and duration of bisphosphonate treatment for AI-induced bone loss remains undefined.
The use of aromatase inhibitors (AIs) in the treatment of breast cancer has expanded with randomized trials showing that AIs are superior to tamoxifen in the metastatic and adjuvant treatment settings in postmenopausal women. The current American Society of Clinical Oncology (ASCO) and International guidelines recommend either initial treatment with AIs or switching to AIs 2–3 years after tamoxifen in postmenopausal women with early stage
breast cancer.[1,2] AIs inhibit the cytochrome P450 (CYP) 19 isoenzyme[3] responsible for the peripheral conversion of androgens to estrogens.[4] Estrogens maintain bone mass and treatment with AIs result in bone loss as a result of estrogen deficiency.[
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