Maturitas 66 (2010) 291–297
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Maturitas
journal homepage: www.elsevier.com/locate/maturitas
Vitamin D deficiency and bone mineral density in postmenopausal women
receiving aromatase inhibitors for early breast cancer
Xavier Nogues
a,∗,1
, Sonia Servitja
b,1
, Maria Jesus Pe ˜ na
a
, Daniel Prieto-Alhambra
a,c
, Rosa Nadal
b
,
Leonardo Mellibovsky
a
, Joan Albanell
b
, Adolfo Diez-Perez
a
, Ignasi Tusquets
b
a
Internal Medicine Department, URFOA-IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Passeig Maritim 25-29, 08003 Barcelona, Spain
b
Medical Oncology Department, Breast Cancer Unit, Molecular Therapeutics and Biomarkers in Breast Cancer, Cancer Research Program, IMIM-Hospital del Mar,
Autonomous University of Barcelona, Barcelona, Spain
c
Institut Catala de la Salut, IDIAP Jordi Gol, Primary Care Research Institute, Barcelona, Spain
article info
Article history:
Received 17 November 2009
Received in revised form 15 March 2010
Accepted 16 March 2010
Keywords:
Breast cancer
Aromatase inhibitors
Vitamin D
Osteoporosis
abstract
Objective: Aromatase inhibitors (AI) treatment leads to an increased risk of bone loss and fractures. In a
group of women with early breast cancer (EBC) and baseline Vitamin D deficiency (<30 ng/ml) who are
treated with AI, we aim to describe: serum levels of Vitamin D, bone mineral density (BMD), calcium
intake, and the increase of serum 25(OH)D accomplished in 3 months of treatment with Vitamin D
supplements.
Study design: Prospective, non-randomized clinical trial.
Methods: In 232 consecutively included women with EBC in treatment with AI, we assessed baseline
calcium intake, serum levels of 25(OH)D, BMD and, spine X-ray. All received Calcium and Vitamin D
supplements, and those with vitamin deficiency received 16,000 IU Vitamin D every 2 weeks. Serum
levels of 25(OH)D were newly assessed after treatment. All the baseline evaluation was performed before
starting AI treatment.
Results: Mean age at baseline (±SD) was 63.2 ± 8.8 years. In 150 (64.9%) cases, the women had been
treated previously with tamoxifen; 101 (43.7%) started exemestane, 119 (51.5%) letrozole, and 11 (4.8%)
anastrozole. The AI were initiated within 6 weeks after surgery or after the last cycle of chemotherapy.
At baseline, 88.1% had 25(OH)D levels <30 ng/ml, 21.2% had severe deficiency (<10 ng/ml), and 25% of
the participants had osteoporosis. Mean daily calcium intake was low (841 ± 338).
We found a significant association between 25(OH)D levels and BMD at baseline, which remained
significant in femoral neck BMD after multivariate adjustment.
Plasma 25(OH)D levels improved significantly at 3 months follow-up in those treated with high dose
Vitamin D supplements: mean increase 32.55 ng/ml (95%CI 28.06–37.03).
Conclusions: Our study suggests a high prevalence of commonly unrecognized Vitamin D deficiency in
women with EBC treated with AI, a known osteopenic agent. Our results support the need for a routine
assessment of 25(OH)D levels and, when necessary, supplementation in these patients.
© 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Breast cancer is the most prevalent type of cancer in women
and the second highest cancer-related cause of death in developed
countries [1]. Fortunately, the survival of breast cancer patients
has improved in recent years, and many patients are considered
long-term survivors. A major advance in recent years has been the
incorporation of aromatase inhibitors (AI) in the adjuvant hormonal
therapy of postmenopausal women with receptor-positive breast
∗
Corresponding author. Tel.: +34 93 248 31 47; fax: +34 93 248 32 57.
E-mail address: xnogues@hospitaldelmar.cat (X. Nogues).
1
These authors contributed equally to this work.
cancer [2]. This improvement has led to a review of quality of life
issues, particularly those related with adjuvant treatments.
Aromatase inhibitors (letrozole, anastrozole and exemes-
tane) massively deplete circulating estrogens in postmenopausal
women. Their use has been correlated with an increased risk of
bone loss and fractures in women receiving these drugs for 2–5
years as adjuvant treatment. Although practical guidelines have
been developed to help prevent and manage the bone loss asso-
ciated with the adjuvant use of AI, the value of routine assessment
of Vitamin D levels remains a topic of discussion.
Vitamin D plays an essential role in calcium homeostasis and
bone metabolism. The importance of optimal plasma concentration
of 25-hydroxyvitamin (25(OH) D) for several health outcomes is
addressed in a recent meta-analysis by Bischoff-Ferrari et al. [3],
0378-5122/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.maturitas.2010.03.012