Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG

Abstract

Background: Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL).

Patients and methods: A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety.

Results: Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL.

Conclusions: In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>-1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

Keywords: Bisphosphonate; Breast cancer; Denosumab; Endocrine treatment; Fracture; Osteoporosis.

Fig. 1

Recommended algorithm for managing bone health in women receiving aromatase inhibitor (AI) therapy for breast cancer. *If patients experience an annual decrease in bone mineral density (BMD) of ≥10% (using the same DXA absorptiometry machine), secondary causes of bone loss such as vitamin D deficiency should be evaluated and antiresorptive therapy initiated. Use lowest T-score from 3 sites. Abbreviations: AI, aromatase inhibitor; BMD, bone mineral density; BMI, body mass index.

Fig. 2

Effects of adjuvant bisphosphonates on disease recurrence (A), bone recurrence (B) and breast cancer mortality (C) in postmenopausal women. Data from the EBCTCG meta-analysis of randomized clinical trials .

Fig. 3

*If not clinically assessable i.e. hysterectomy/IUD then ensure serum FSH is in postmenopausal range. Ensure patient is not receiving concurrent therapies that can affect the HPG axis. δInclude vitamin D 1000-2000IU and calcium 1000 mg/day.