Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer

Servitja, Sònia; Nogués, Xavier; Prieto-Alhambra, Daniel; Martinez-García, Maria; Garrigós, Laia; Peña, María J.; Ramón, Marta de; Díez-Pérez, Adolfo; Albanell, Joan; Tusquets, Ignasi

doi:10.1016/j.breast.2011.09.001

Cited by 44 publications

(26 citation statements)

References 35 publications

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“…While the association between vitamin D levels and breast cancer risk/prognosis is still controversial, the U-shaped relationship between 25-OH vitamin D levels and cancer or mortality risk observed in different studies suggests the need to avoid both deficient and too high levels [52,60,61]. A serum concentration of 25-OH vitamin D ≥40 ng/ml was associated with lower incidence of arthralgia in a specific prospective cohort study specifically designed to establish optimal levels of vitamin D for the prevention of AI-induced arthralgia [62], while the risk of arthralgia in patients with low concentration of 25-OH vitamin D (≤30 ng/ml) was confirmed in a separate study [63]. A weekly dose of up to 10,000 IU may thus be recommended in women with breast cancer based on recent international guidelines [64].…”

Section: Calcium and Vitamin D Supplementationmentioning

confidence: 99%

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper

et al. 2012

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Summary Aromatase inhibitors (AIs) are widely used in women with breast cancer, but they are known to increase bone loss and risk of fractures. Based on available evidence and recommendations, an ESCEO working group proposes specific guidance for the prevention of AIs-induced bone loss and fragility fractures. Introduction Aromatase inhibitors (AIs) are now the standard treatment for hormone receptor-positive breast cancer. However, deleterious effects of AIs on bone health have beenreported. An ESCEO working group proposes guidance for the prevention of bone loss and fragility fractures in postmenopausal women with breast cancer receiving AIs. Methods A panel of experts addressed the issue of skeletal effects of AIs and effectiveness of antifracture therapies for the prevention of AI-induced bone loss and fractures. Recommendations by national and international organizations, and experts' opinions on this topic were evaluated. Results All aromatase inhibitors are associated with negative effects on the skeleton, resulting in bone loss and increased risk of fragility fractures. Current guidelines suggest approaches that differ both in terms of drugs proposed for fracture prevention and duration of treatment. Conclusion The ESCEO working group recommends that all AI-treated women should be evaluated for fracture risk. Besides general recommendations, zoledronic acid 4 mg i.v. every 6 months, denosumab s.c., or possibly oral bisphosphonates should be administered for the entire period of AI treatment to all osteoporotic women (T-score hip/spine <−2.5 or ≥1 prevalent fragility fracture), to women aged ≥75 irrespective of BMD, and to patients with T-score <−1.5+≥1 clinical risk factor or T-score <−1.0+≥2 clinical risk factors. Alternatively, therapy could be considered in patients with a FRAX-determined 10-year hip fracture probability ≥3%.

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Section: Calcium and Vitamin D Supplementationmentioning

confidence: 99%

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper

et al. 2012

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“…Only 10% had normal 25(OH)D concentrations, as defined by > 30 ng/ml. Vitamin D insufficiency (concentrations < 30 ng/ml) was observed in 90% of the women (Figure 2) [Nogues et al 2010;Servitja et al 2012]. At baseline, 26% of the women had a normal BMD, 53.7% had osteopenia, and 19.4% had osteoporosis (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

“…In our department, the technique has an in vivo coefficient of variation of 1.0% for LS, 1.65% for FN, and 1.60% for TH measurements. BMD was assessed at baseline and will be repeated at 12 months and then annually, according to the study protocol [Nogues et al 2010;Servitja et al 2012].…”

Section: Measurementsmentioning

confidence: 99%

Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

et al. 2015

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Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables.

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“…It is noteworthy that the rates of BMD loss in LS were at all times higher than FN. In this regard, it is known that trabecular bone is weaker than the cortical in response to AI therapy 17 . Overall, the patients in the cohort B-ABLE lose less BMD compared to previously reported by FFS.…”

Section: Discussionmentioning

confidence: 99%

Evolución de la DMO durante el tratamiento con inhibidores de aromatasa y su relación con el gen CYP11A1: estudio prospectivo de la cohorte B-ABLE

Rodríguez-Sanz

Prieto‐Alhambra

Servitja

et al. 2015

Rev Osteoporos Metab Miner

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SummaryObjectives: The aim of this study was to analyze bone mineral density (BMD) changes throughout aromatase inhibitor (AI) treatment in clinical cases and also consider its association with the CYP11A1 gene and the BMD variation after treatment. Material and methods: The B-ABLE cohort is a prospective study of postmenopausal women with breast cancer, in AI treatment. BMD variation was analyzed during AI treatment, as well as the differences those patients who were treated and not treated previously with tamoxifen (TMX). Three polymorphisms (rs4077581, rs11632698 and rs900798) of the CYP11A1 gene were genotyped for their association with BMD variation. Results: TMX-treated patients presented more rapid BMD loss than those who did not undergo prior TMX treatment (60% less in spine and 46% in femur at 2 years and 70% less in the spine and 63% in the femur at 3 years). However, no significant BMD loss was detected after treatment in either group. The 3 CYP11A1 gene polymorphisms were significantly associated with BMD variation in the femur at the end of the treatment. Conclusions: BMD was reduced more rapidly in patients with prior TMX treatment than in those who only received AI, although no significant differences were detected after treatment. The 3 CYP11A1 gene polymorphisms were associated with BMD variation in response to AI treatment.

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Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer

Abstract: Low bone mass, prevalent fractures and vitamin D insufficiency were highly prevalent among candidates to adjuvant AI for EBC. Therefore, it is crucial to assess BMD, prevalent fractures and 25(OH)D concentrations before starting AI therapy and during follow-up.

Cited by 44 publications

References 35 publications

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper

Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

Evolución de la DMO durante el tratamiento con inhibidores de aromatasa y su relación con el gen CYP11A1: estudio prospectivo de la cohorte B-ABLE

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