Negative Impact of Aromatase Inhibitors on Proximal Femoral Bone Mass and Geometry in Postmenopausal Women with Breast Cancer

Abstract

Aromatase inhibitors (AIs), the standard therapy for estrogen receptor- or progesterone receptor-positive breast cancer in postmenopausal women, lead to increased hip fractures in breast cancer patients. To investigate the mechanism of increased incidence of hip fractures in breast cancer patients treated with AIs, we evaluated bone mineral density (BMD) in the cortical and trabecular compartments and assessed femoral geometry using quantitative computed tomography (QCT) in breast cancer patients. In total, 249 early breast cancer patients who underwent QCT in their fifties (mean age 54.3 years) were retrospectively analyzed. Proximal femoral BMD and geometrical parameters were compared. In all regions of the proximal femur, cortical areal BMDs were lower in the AI group than in the non-AI group (p < 0.05). Cortical thickness of the femoral neck, trochanter, and total hip was significantly lower in the AI group compared with the non-AI group (p < 0.05). Analysis of the narrowest section of the femoral neck showed significantly thinner cortical bone and smaller cortical area in the AI group than in the non-AI group (p < 0.05), especially in the superoposterior quadrant. Bone strength parameters in the femoral neck, such as the section modulus and cross-sectional moment of inertia, were significantly lower in the AI group than in the non-AI group (p < 0.05). In conclusion, AI treatment in breast cancer patients is associated with deterioration of femoral cortical BMD and geometry, which could contribute in site-specific weakened bone strength and increased incidence of hip fractures.

The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions

“…HR-pQCT has been used in other disorders such as celiac disease, COPD, carcinoid syndrome, hemophilia, Gaucher and Pompe disease, hypophosphatasia, and X-linked hypophosphatasia [119][120][121][122][123][124][125][126]. In addition, HR-pQCT has been used to evaluate the impact of medications known to have a deleterious effect on bone, such as aromatase inhibitors or androgen deprivation therapy [127,128]. Altogether, these studies demonstrate the potential of HR-pQCT to assess underlying structural defects in these rare bone disorders and in non-skeletal conditions and treatments that impact the skeletal system.…”

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

“…However, aromatase inhibitors (AI) have now replaced tamoxifen as the treatment of choice for hormone-responsive breast cancer in most postmenopausal women because of both better efficacy and fewer serious side effects such as induction of uterine cancers and thromboembolic events [6], [7], [10], [11]. However, because AIs prevent peripheral estrogen production, they suppress estrogen levels beyond that attained from a natural menopause, thereby leading to accelerated bone loss and an increased fracture risk [12], [13], [14], [15].…”

“…AI-associated bone loss (AIBL) leads to a marked increase of bone resorption, with a 2–4 fold increased bone loss compared to physiologic postmenopausal BMD loss [12], [15], [17], [18], [19], [20], [21], [22], [23], [24]. As a result, women receiving adjuvant AI therapy for breast cancer are at increased risk for fractures [25], [26], [27], [28], which leads to increased morbidity and mortality [29].…”

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview

“…In contrast to GCs, AIs predominantly affect cortical bone that composes 80% of bone tissue and mostly determines bone strength. AI-associated bone loss (AIBL) leads to a marked increase of bone resorption, with a 2to 4-fold increased bone loss compared to physiologic postmenopausal BMD loss (133). Fractures occur at younger ages and higher BMD than expected for patients in this age group without breast cancer.…”