Aromatase inhibitor‐induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients

Yonehara, Yukie; Iwamoto, Ichiro; Kosha, Shoichiro; Rai, Yoshiaki; Sagara, Yoshiatsu; Douchi, Tsutomu

doi:10.1111/j.1447-0756.2007.00634.x

Cited by 16 publications

(3 citation statements)

References 21 publications

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“…In our study, BMD loss was observed in 62.0% of patients in the ANA alone group, while only 26.9% of patients had a BMD loss in the combination bisphosphonate group. The findings of AIinduced BMD loss and its prevention by bisphosphonates agree with previous reports [6,[15][16][17][18][19][20]. In postmenopausal women, there is an established concept that circulating estrogens, most of which are minimal and unmeasurable by conventional RIA methods, are derived from aromatization in peripheral adipose tissue [21].…”

Section: Discussionsupporting

confidence: 90%

Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients

Sagara¹,

Kosha

Baba³

et al. 2009

Breast Cancer

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Section: Discussionsupporting

confidence: 90%

Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients

Sagara¹,

Kosha

Baba³

et al. 2009

Breast Cancer

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“…An assessment of fracture risk based upon clinical risk factors, coupled with dual‐energy X‐ray absorptiometry (DXA) of the hip and lumbar spine is reasonable in older patients (>60 years) initiating AIs . Bisphosphonate therapy or denosumab could be considered in those assessed as being at high baseline fracture risk (e.g. women with established osteoporosis or FRAX‐determined 10‐year probability of major osteoporotic fracture >20%.…”

Section: Hormonal Treatmentsmentioning

confidence: 99%

Adverse skeletal effects of drugs – beyond Glucocorticoids

O'Sullivan

Grey

2014

Clinical Endocrinology

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SummaryOsteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management.

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“…In a study by Yonehara et al . [44], there was a significant increase in BMD in a group of women treated with bisphosphonate. The study, however, included only 17 patients.…”

Section: Treatment and Prophylactics Of The Aromatase Inhibitor‐inducmentioning

confidence: 99%

The Effect of Aromatase Inhibitors on Bone Metabolism

Folkestad

Bjarnason

Bjerregaard

et al. 2008

Basic Clin Pharma Tox

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Aromatase inhibitors increase the disease-free survival in patients with receptor-positive breast cancer. Aromatase is a cytochrome P450 enzyme complex catalysing the conversion of androgens to oestrogens. These properties cause a significant increase in bone loss. In this MiniReview , we present data from the aromatase inhibitor studies and the studies designed to investigate aromatase inhibitor effect on bone metabolism. At the cellular level, oestrogen has profound effects on both osteoblasts and osteoclasts. Oestrogen decreases the osteoblastic production of resorptive cytokines and simultaneously increases the production of antireceptive cytokines, which leads to increased osteoclastic apoptosis and increased osteoblastic activity. Aromatase inhibitors inhibit the endogenous production of oestrogen by 50 -90%. Studies designed to look at the effect of aromatase inhibitors on bone mineral density have shown a significant decrease in bone mineral density of the femoral neck in the aromatase inhibitor groups compared to placebo groups. Placebo-controlled studies lack statistical power to detect changes in fracture incidence; however, aromatase inhibitors increase the incidence of fractures in comparison with tamoxifen. We conclude that treatment with aromatase inhibitors leads to an increased bone loss and thus an increase in the risk of fractures in women with breast cancer.The survival from breast cancer has increased over the last decades due to improved surgery, radiotherapy and pharmacological therapy [1]. One of the major advances has been the introduction of aromatase inhibitors. Breast cancer tumours are oestrogen-sensitive in about two-thirds of all cases [2]. Tamoxifen has been the gold standard treatment for these tumours; however, some tumours develop resistance [3]. Aromatase inhibitors reduce the endogenous oestrogen synthesis by 50 -90% and increase the 5-year disease-free survival rate in post-menopausal women significantly alone or in sequence with tamoxifen [4 -8]. These studies also show that high-risk, receptor-positive patients treated with aromatase inhibitors had fewer side effects than those patients treated with tamoxifen [4][5][6][7][8]. Treatment for receptorpositive breast cancer varies and depends on whether the woman is pre-or post-menopausal, on tumour size and stage, and on the extension of metastases if such are present, but may consist of, for example, 2.5 years of tamoxifen followed by 2.5 years of aromatase inhibitors. Aromatase inhibitors are the drugs of choice for patients with receptorpositive tumours relapsing after their primary treatment. Ongoing studies compare 5 years of aromatase inhibitors with the current regime [the Breast International Group (BIG) 1-98, TEAM] [9]. While results from these trials are not yet published, they could potentially change standard therapy which will accentuate the question of the long-term side effects of aromatase inhibitor treatment. Osteoporosis is common in post-menopausal women. About 40-50% of these women will have at l...

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Aromatase inhibitor‐induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients

Abstract: AI carries a potential risk of bone mineral loss despite the short therapy duration. Bisphosphonate has a preventive effect on this loss.

Cited by 16 publications

References 21 publications

Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients

Adverse events and bone health during anastrozole therapy in postmenopausal Japanese breast cancer patients

Adverse skeletal effects of drugs – beyond Glucocorticoids

The Effect of Aromatase Inhibitors on Bone Metabolism

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