Aromatase Inhibitor Induced Bone Loss: Do International Guidelines Accurately Stratify Fracture Risk and Selection of Anti-Osteoporosis Treatment?

Abstract Introduction: Aromatase inhibitors (AI) are used for adjunctive treatment of estrogen receptor-positive (ER+) breast cancer. Aromatase converts androgens to estrogens in the ovaries and peripheral tissues such as adipose, liver, muscle, and breast. In breast, estrogens increase cell proliferation in both normal and ER+ malignant tissue. AIs globally suppress estrogen production, and thereby can decrease tumor progression. However, in bone, estrogens suppress osteoclast activity and decrease bone resorption so AI use results in increased bone resorption and decreased bone mineral density (BMD). Several guidelines exist to direct management of AI-associated bone loss, but it is unclear whether adherence to these guidelines translates to decreased fracture risk. The International Osteoporosis Foundation (IOF) et al 2017 guidelines for the prevention of osteoporotic fractures in patients treated with AI recommended BMD measurement at the onset of AI use and use of anti-osteoporosis therapy (anti-OP) in those who met T-score and clinical risk factor (CRF) criteria. Hypothesis: We explored application of these guidelines and whether they were able to stratify patients according to risk, initiation of treatment, and fracture outcomes. Methods: 1517 charts were extracted from the electronic medical record (EMR) of a tertiary academic medical center based on history of breast cancer and use of AIs between 2008 and 2017. Charts were retrospectively analyzed to determine baseline BMD, osteoporosis risk factors, duration of AI use, duration of anti-OP therapy, and fractures. The IOF criteria were applied to each patient to determine applicability of anti-OP therapy. Fracture rates were compared using chi square test or Fisher’s exact test. Results: 1517 patients were included in the analysis. Regardless of whether criteria were met for treatment based on baseline BMD and CRF, the fracture rate was significantly higher in the treated versus the untreated group, 13.78% (CI: 9.56–18.99) versus 2.24% (p < 0.0001, CI: 1.51–3.21). Similarly, among those that met criteria, the fracture rate was significantly higher in the treated versus the untreated group, 10.24% (CI: 5.56–16.87) versus 2.61% (p = 0.0005, CI: 1.20–4.89). There was no significant difference in fractures between those who did versus did not meet treatment criteria, 4.66% (CI: 2.94–6.97) versus 3.64% (p = 0.34, CI 2.59–4.96). Conclusions: This retrospective EMR analysis of 1517 breast cancer patients on AIs between 2008 and 2017 observed a higher fracture incidence in patients who received anti-OP treatment compared to those who did not, regardless of meeting criteria for treatment per the IOF guidelines. It is possible that patients who initiated anti-OP therapy had additional CRFs not captured in the EMR and not factored into our analyses.