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Aromatase Inhibitors and Fractures: Reducing the Risk

Dr. Eleonora Teplinsky, from Valley Health - The Icahn School of Medicine, Mount Sinai, presents during the 2022 Evolution Conference in Boston, MA.

At this year’s ‘Evolution’ breast cancer educational conference, Dr Eleonora Teplinsky, MD

discussed considerations for managing older (post-menopausal) patients with breast cancer, specifically bone health, which can be adversely impacted by the long-term use of aromatase inhibitors (AI). She noted that the AIs are known to cause an increase in markers of bone turnover such as urine N-telopeptide (NTX) and serum C-telopeptide (CTX) whereas such changes are not seen with drugs like tamoxifen in the postmenopausal population. As such, in postmenopausal patients, AI use is known to be associated with an increased risk for complications such as bone loss and fractures.

She noted that the major clinical trials of the AIs, including the ATAC study (Arimidex, Tamoxifen, Alone or in Combination) and the IES (Intergroup Exemestane Study) reported a loss of bone mineral density (BMD) for patients in the AI group, relative to those on tamoxifen. She also cited evidence for increased fracture risk with AI use (in one study, a 47% relative risk, and a 2.2% absolute fracture risk), for patients on AIs, as compared with tamoxifen. Some studies have also suggested that discontinuing AIs can reduce fracture risk.

Dr Teplinsky summarized the major clinical risk factors for bone fracture, which include advanced age, a prior fracture, smoking, excessive alcohol consumption, low body weight, and history of secondary osteoporosis. She also noted the availability of clinical assessment tools such as the FRAX which can help identify patients at higher risk of fracture while on AI therapy. Some of the non-pharmacologic methods for osteoporosis management include reducing/stopping smoking and reducing alcohol consumption. Adequate Vitamin D and calcium intake can also help to reduce bone loss and promote a positive calcium balance. Dr Teplinsky emphasized the current recommendations for 1200 mg elemental calcium and 800 or more IU of Vitamin D daily for her patients on AI therapy. Also critical in non-pharmacologic management is exercise, including balance, endurance, and strength training.

Pharmacologic management to treat and prevent bone loss with AIs is driven by the T-score from bone mineral density assessments. For example, for patients with a T-score of > -2.0, lifestyle changes and calcium/Vitamin D supplementation are indicated, whereas if T-score is < -2.0, additional anti-resorptive bone therapies such as denosumab or bisphosphonates should be added to the regimen. Dr Teplinsky noted the generally mild and manageable tolerability of the available anti-resorptive agents, and her preference for the intravenous (IV) therapies (e.g., denosumab, zoledronic acid) over oral therapies (e.g., clodronate, ibandronate) to ensure good patient compliance. There may, however, be some concerns with cost and coverage of these treatments for some patients.

Dr Teplinsky also briefly reviewed some of the data concerning the reduction in breast cancer recurrence that has been observed for patients taking bisphosphonate therapy (oral clodronate or ibandronate, or IV zoledronic acid) relative to those on placebo. One study of nearly 12,000 women showed significant reductions in recurrence, bone recurrence, and breast cancer mortality for patients on bisphosphonate therapy relative to those on placebo. Results have been less consistent for denosumab, although a recent update from the ABCSG18 study presented at ASCO 2022 showed a significant benefit in reducing recurrence and a trend toward better overall survival with denosumab relative to placebo. Bone is the most common site of metastasis for breast cancer, and Dr Teplinsky summarized some of the major complications of bone metastases, including pain, reduced performance status, skeletal-related events (SREs) and impaired quality of life (QoL). She emphasized that breast cancer patients with bone metastases should be treated with bone-modifying agents to prevent SREs, and there is also evidence for a modest pain control benefit with the therapy.

In summary, Dr Teplinsky highlighted the risk for bone loss and increased fracture risk for patients with breast cancer receiving AI therapy. Pharmacologic management should be used in these patients to reduce fracture risk, and may have the added benefit of reducing breast cancer recurrence; research to better identify which patients will benefit the most from this therapy is ongoing.

See more from the 2022 Evolution Conference here.

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