Elsevier

Bone

Volume 97, April 2017, Pages 147-152
Bone

Full Length Article
Morphometric vertebral fractures in breast cancer patients treated with adjuvant aromatase inhibitor therapy: A cross-sectional study

https://doi.org/10.1016/j.bone.2017.01.013Get rights and content

Highlights

  • High rate of vertebral fractures was found in aromatase inhibitor (AI)-treated women.

  • The rate of vertebral fractures was not associated with duration of AI therapy.

  • High prevalence of vertebral fractures was observed even in women with normal BMD.

  • Serum parathyroid levels increased during AI therapy notwithstanding normal vitamin D status.

Abstract

Background

The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear.

Objective

In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels.

Results

We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One-hundred-sixty-nine women were AI-naïve, and 94 were AI-treated. AI-treated patients had lower BMD at total hip (p = 0.01) and lumbar spine (p = 0.03), higher serum vitamin D (p < 0.001) and parathyroid hormone (p = 0.006) values as compared to AI-naïve patients. The prevalence of VFs was 18.9% in AI-naïve patients, and 31.2% in those assessed during AI therapy (odds ratio 1.90, 95% CI 1.1–3.5, p = 0.03). In AI-naïve patients, VFs were associated with older age (p = 0.002) and lower BMD values at femoral neck (p = 0.04) and total hip (p = 0.007), whereas VFs occurred without association with any parameter analyzed in AI-treated patients. In AI-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p = 0.31).

Conclusions

In women with early BC, AI therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of AI-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with AIs.

Introduction

Breast cancer (BC) is the most common invasive cancer and accounts for about 25% of all tumors in women. About 80% of BCs are hormone receptor-positive and can benefit from endocrine therapy. Aromatase inhibitors (AIs) are the most frequently used endocrine therapy in postmenopausal women with early stage BC [1]. Due to the reduction in circulating estrogen levels, AIs may compromise bone health [2]. Previous studies have clearly demonstrated a decrease in bone mineral density (BMD), an increase in bone turnover, and an increase in fracture risk during AI therapy [3], [4], [5], [6], [7], [8], [9]. However, almost all studies used questionnaires and databases to investigate the risk of clinical fractures in AI-treated women without providing reliable data on vertebral fractures (VFs) in this clinical setting. As a matter of fact, VFs are the most common complication of osteoporosis [10], and are associated with decreased survival [11], impaired quality of life [12], and an increased risk of future fractures in the general population [13]. Since only about one-third of VFs is clinically recognized [10], the radiological and morphometric approach has emerged as the method of choice for evaluating the true prevalence and incidence of these fractures in population and clinical studies [14].

The present single-center study was designed to explore the prevalence and determinants of VFs in a group of postmenopausal women with endocrine-sensitive early BC exposed to different periods of AI therapy compared with a group of AI-naïve patients.

Section snippets

Study design

This was a cross-sectional study conducted at Spedali Civili Hospital of Brescia. The local independent ethics committee approved the study protocol and informed consent forms.

Study population

Postmenopausal women with hormone receptor-positive early stage BC referred and followed up at the Medical Oncology Unit and Breast Unit were consecutively selected: 169 patients were studied before starting adjuvant AI therapy (AI-naïve group) and 94 patients were undergoing treatment with AI therapy (AI-treated group).

Results

Two-hundred-sixty-three patients were included in the study from September 2013 to July 2016. The characteristics of AI-naïve patients (169 patients) and those exposed to AIs (94 patients) are shown in Table 1. The two groups showed no statistically significant differences in age, body mass index (BMI), duration of postmenopausal period and prior chemotherapy (neoadjuvant or adjuvant).

At the study entry, 55 AI-treated patients (58.5%) were receiving vitamin D supplementation, and 22 patients

Discussion

In this study, women with BC undergoing treatment with AIs showed a higher prevalence of radiological VFs as compared to women with BC before starting AI therapy. Interestingly, VFs were shown to occur independently of BMD values and vitamin D status.

Endocrine therapy with AIs for five years represents the standard adjuvant therapy for early stage hormone receptor-positive postmenopausal BC [17]. Despite AIs availability in clinical practice for many years, their impact on fracture risk is not

Conflicts of interests

Rebecca Pedersini, Sara Monteverdi, Gherardo Mazziotti, Vito Amoroso, Elisa Roca, Filippo Maffezzoni, Lucia Vassalli, Filippo Rodella, Stefano Frara, Anna Maria Formenti, Roberto Maroldi, Alfredo Berruti, Edda Lucia Simoncini, and Andrea Giustina declare that they have no conflict of interest.

Funding

This work was partially supported by Fondazione Beretta (grant number 2016), Brescia, Italy.

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