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Effect of Denosumab on Glucose Homeostasis in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors: A Pilot Study.

Abstract：

Background:Aromatase inhibitors in women with breast cancer have been associated with cancer treatment-induced bone loss (CTIBL), increased fracture risk, and impairment of glucose metabolism. Denosumab (Dmab), a monoclonal antibody against RANKL, which is a key regulator of the osteoclast activity, is effective as an antiresorptive agent in the treatment of CTIBL. Since RANKL/RANK pathway may contribute to the pathogenesis of glucometabolic disorders, it has been suggested that Dmab may improve glucose homeostasis. Our pilot study evaluated the effect of a single administration of 60 mg Dmab on glucose metabolism in a cohort of women with breast cancer treated with aromatase inhibitors. Methods:Fifteen postmenopausal nondiabetic women were prospectively enrolled. Oral glucose tolerance test (OGTT) and metabolic parameters, including FGF21, were assessed at baseline and one month after Dmab injection. Midterm glucose control was evaluated by measuring glycated haemoglobin (HbA1c) levels 5 months after Dmab. Results:Parameters of glucose metabolism were not different one month after Dmab but circulating FGF21 levels significantly decreased (128.5 ± 46.8 versus 100.2 ± 48.8 pg/mL; p=0.016). Considering patients with insulin resistance at baseline (HOMA-IR > 2.5 and Matsuda Index < 2.5; n = 5), reduced mean fasting insulin levels (16.3 ± 4.9 versus 13.5 ± 3.5 mcU/mL; p=0.029) and increased insulin sensitivity index QUICKI (0.317 ± 0.013 versus 0.327 ± 0.009; p=0.025) were found. Nonetheless, HbA1c increased 5 months after Dmab (36.0 ± 2.3 versus 39.6 ± 3.1 mmol/mol; p=0.01). Conclusions:Although RANKL blockade induced a short-term positive effect on insulin sensitivity, particularly in insulin-resistant patients, a benefit on long-term glucose metabolism was not evident. In conclusion, Dmab is safe for glucose metabolism in aromatase inhibitor-treated women with breast cancer.

journal_name

Int J Endocrinol

journal_title

International journal of endocrinology

authors

Rossini A,Frigerio S,Dozio E,Trevisan R,Perseghin G,Corbetta S

doi

10.1155/2020/1809150

subject

Has Abstract

pub_date

2020-11-06 00:00:00

pages

1809150

eissn

1687-8337

issn

1687-8345

journal_volume

2020

pub_type

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Effect of Denosumab on Glucose Homeostasis in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors: A Pilot Study.