Fracture incidence after 3 years of aromatase inhibitor therapy

Bouvard, Béatrice; Soulié, P; Hoppé, Emmanuel; Georgin-Mège, M.; Royer, Mary G.; Mesgouez-Nebout, N.; Lassalle, Christian; Cellier, P.; Jadaud, É.; Abadie‐Lacourtoisie, Sophie; Tuchais, C.; Vinchon-Petit, S.; Audran, Maurice; Chappard, Daniel; Legrand, Érick

doi:10.1093/annonc/mdu008

Cited by 36 publications

(16 citation statements)

References 20 publications

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Section: Introductionmentioning

confidence: 99%

“…In postmenopausal women, the only sources of estrogens are through the aromatase function in peripheral tissues and through steroid sulfatase activity (Reed et al 2005), which is also active in bone (Muir et al 2004). Therefore, the aromatase inhibition, especially at the bone tissue level, would cause a major BMD loss (Bouvard et al 2014). However, remnant estrogen levels after aromatase inhibition may modulate the degree of bone loss.…”

Section: Introductionmentioning

confidence: 99%

“…Several prospective studies and clinical trials have noted the need for assessment and treatment of these musculoskeletal adverse events (Reid et al 2008, Brufsky et al 2009, Servitja et al 2012. In particular, bone mineral density (BMD) reduction and fracture incidence associated with AI therapy can be significantly reduced by oral bisphosphonates (BP) treatment (Bouvard et al 2014).We are currently conducting a prospective, nonselected, observational, clinical cohort study (BarcelonaAromatase induced bone loss in early breast cancer (B-ABLE)) to investigate the musculoskeletal side effects of AI in postmenopausal women with early breast cancer. Previously, we reported a genetic association with AI-related arthralgia and therapy discontinuation in this cohort.…”

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confidence: 99%

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CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

Rodríguez-Sanz

Garcia-Giralt

Prieto-Alhambra

et al. 2015

Journal of Molecular Endocrinology

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Aromatase inhibitors (AIs) used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer cause diverse musculoskeletal side effects that include bone loss and its associated fracture. About half of the 391 patients treated with AIs in the Barcelona-Aromatase induced bone loss in early breast cancer cohort suffered a significant bone loss at lumbar spine (LS) and/or femoral neck (FN) after 2 years on AI-treatment. In contrast, up to one-third (19.6% LS, 38.6% FN) showed no decline or even increased bone density. The present study aimed to determine the genetic basis for this variability. SNPs in candidate genes involved in vitamin D and estrogen hormone-response pathways (CYP11A1, CYP17A1, HSD3B2, HSD17B3, CYP19A1, CYP2C19, CYP2C9, ESR1, DHCR7, GC, CYP2R1, CYP27B1, VDR and CYP24A1) were genotyped for association analysis with AI-related bone loss (AIBL). After multiple testing correction, 3 tag-SNPs (rs4077581, s11632698 and rs900798) located in the CYP11A1 gene were significantly associated (P!0.005) with FN AIBL at 2 years of treatment. Next, CYP11A1 expression in human fresh bone tissue and primary osteoblasts was demonstrated by RT-PCR. Both common isoforms of human cholesterol side-chain cleavage enzyme (encoded by CYP11A1 gene) were detected in osteoblasts by western blot. In conclusion, the genetic association of CYP11A1 gene with AIBL and its expression in bone tissue reveals a potential local function of this enzyme in bone metabolism regulation, offering a new vision of the steroidogenic ability of this tissue and new understanding of AI-induced bone loss. Journal of Molecular EndocrinologyResearch M RODRI´GUEZ-SANZ and others CYP11A1 is associated with AI-related bone loss 55:1 69-79http://jme.endocrinology-journals.org Ñ 2015 Society for Endocrinology DOI: 10.1530/JME-15-0079Printed in Great BritainPublished by Bioscientifica Ltd. IntroductionAromatase inhibitors (AIs) are commonly used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. Although AIs are generally well tolerated with few serious adverse events, a number of musculoskeletal side effects affecting quality of life have been noted and often lead to discontinuation of therapy (Eastell et al. 2006, Henry et al. 2008.The most common side effects reported with AIs are exacerbation of menopausal symptoms as a result of low estrogen levels; these include pain syndromes, bone loss and associated fracture , Laroche et al. 2014. Several prospective studies and clinical trials have noted the need for assessment and treatment of these musculoskeletal adverse events (Reid et al. 2008, Brufsky et al. 2009, Servitja et al. 2012. In particular, bone mineral density (BMD) reduction and fracture incidence associated with AI therapy can be significantly reduced by oral bisphosphonates (BP) treatment (Bouvard et al. 2014).We are currently conducting a prospective, nonselected, observational, clinical cohort study (BarcelonaAromatase induced bone loss in early breast cancer (B-ABLE...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

Rodríguez-Sanz

Garcia-Giralt

Prieto-Alhambra

et al. 2015

Journal of Molecular Endocrinology

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“…In this study, Bouvard and coworkers described BMD changes as well as observed incidence of fracture after 3 years of AI therapy reporting BMD decreases by 3.5% at the LS and 2.0% at the FN in BP-untreated patients (Bouvard et al 2014).…”

Section: Discussionmentioning

confidence: 60%

“…Similarly, in the ARIBON trial, BMD increases were reported at both the LS (5.5%) and the FN (3.0%) for patients treated with ibandronate (Lester et al 2008). By contrast, the recent prospective study of Bouvard and coworkers described no significant increases in BMD after 3 years (Bouvard et al 2014).…”

Section: :4mentioning

confidence: 90%

AI-related BMD variation in actual practice conditions: A prospective cohort study

Rodríguez-Sanz¹,

Prieto‐Alhambra²,

Servitja³

et al. 2016

Endocrine-Related Cancer

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The aim of the study was to evaluate the progression of bone mineral density (BMD) during 3 years of aromatase inhibitors (AI) therapy in actual practice conditions. This prospective, clinical cohort study of Barcelona-Aromatase induced Bone Loss in Early breast cancer (B-ABLE) assessed BMD changes during 3 years of AI treatment in women with breast cancer. Patients with osteoporosis (T score < −2.5 or T score ≤ −2.0) and a major risk factor and/or prevalent fragility fractures were treated with oral bisphosphonates (BPs). Of 685 women recruited, 179 (26.1%) received BP treatment. By the third year of AI therapy, this group exhibited increased BMD in the lumbar spine (LS; 2.59%) and femoral neck (FN; 2.50%), although the increase was significant only within the first year (LS: 1.99% and FN: 2.04%). Despite BP therapy, however, approximately 15% of these patients lost more than 3% of their baseline bone mass. At 3 years, patients without BP experienced BMD decreases in the LS (−3.10%) and FN (−2.79%). In this group, BMD changes occurred during the first (LS: −1.33% and FN: −1.25%), second (LS: −1.19% and FN: −0.82%), and third (LS: −0.57% and FN: −0.65%) years of AI treatment. Increased BMD (>3%) was observed in just 7.6% and 10.8% of these patients at the LS and FN, respectively. Our data confirm a clinically relevant bone loss associated with AI therapy amongst nonusers of preventative BPs. We further report on the importance of BMD monitoring as well as calcium and 25-hydroxy vitamin D supplementation in these patients.

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Effects on the Skeleton from Medications Used to Treat Nonskeletal Disorders

Watts

2018

Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism

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Fracture incidence after 3 years of aromatase inhibitor therapy

Cited by 36 publications

References 20 publications

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

CYP11A1 expression in bone is associated with aromatase inhibitor-related bone loss

AI-related BMD variation in actual practice conditions: A prospective cohort study

Effects on the Skeleton from Medications Used to Treat Nonskeletal Disorders

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