Bone-Related Adverse Effects of Anastrozole

Mechanism and Bone Loss

• Anastrozole causes rapid decline in circulating estrogen, leading to accelerated bone loss and increased bone resorption, as reported by the National Comprehensive Cancer Network 1, 2, 4
• Over 5 years of treatment, anastrozole causes significant BMD decreases: lumbar spine (-6.08%) and total hip (-7.24%), according to the National Comprehensive Cancer Network 2, 3
• This bone loss translates to increased fracture risk (2.93% annual incidence with anastrozole vs 1.9% with tamoxifen in the ATAC trial), as noted by the National Comprehensive Cancer Network 1, 2, 3

Clinical Significance and Fracture Risk

• In the ATAC trial, fracture incidence was 7.1% with anastrozole versus 4.1% with tamoxifen after mean 37 months follow-up (OR 1.34, 95% CI 1.22-1.57), as reported in the Journal of Clinical Oncology 5, 6
• Older age is associated with higher fracture risk in patients on aromatase inhibitors, according to the National Comprehensive Cancer Network 2, 3
• Importantly, fracture rates return to baseline after treatment cessation, suggesting the effect is treatment-related rather than permanent, as noted by the National Comprehensive Cancer Network 1, 2, 3

Management Approach

• Consider baseline and periodic bone mineral density testing, particularly in high-risk patients, as recommended by the National Comprehensive Cancer Network 1
• Bisphosphonates (risedronate, zoledronic acid) effectively preserve BMD in patients receiving anastrozole, according to the National Comprehensive Cancer Network 1, 3
• All patients should receive calcium (1200 mg/d) and vitamin D (400-600 mg) supplementation, as suggested by the Journal of Clinical Oncology 5, 8