Cardiometabolic Effects of Denosumab in Premenopausal Women with Breast Cancer Receiving Estradiol Suppression: RCT

Sabashini K Ramchand; Rudolf Hoermann; Shane White; Belinda Yeo; Prudence A Francis; Cecilia L H Xu; Jeffrey D Zajac; Ego Seeman; Mathis Grossmann

doi:10.1210/clinem/dgae003

Cardiometabolic Effects of Denosumab in Premenopausal Women with Breast Cancer Receiving Estradiol Suppression: RCT

J Clin Endocrinol Metab. 2024 Jan 5:dgae003. doi: 10.1210/clinem/dgae003. Online ahead of print.

Authors

Sabashini K Ramchand^{1

2}, Rudolf Hoermann¹, Shane White^{1

3}, Belinda Yeo^{1

3}, Prudence A Francis⁴, Cecilia L H Xu¹, Jeffrey D Zajac^{1

5}, Ego Seeman^{1

5}, Mathis Grossmann^{1

5}

Affiliations

¹ Department of Medicine, Austin Health, University of Melbourne, Victoria, Australia.
² Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Massachusetts, United States.
³ Olivia Newton-John Cancer & Wellness Centre, Austin Health, Victoria, Australia.
⁴ Peter MacCallum Cancer Centre, Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia.
⁵ Department of Endocrinology, Austin Health, Victoria, Australia.

PMID: 38181438
DOI: 10.1210/clinem/dgae003

Abstract

Context: Menopause is associated with changes in musculoskeletal, body composition, and metabolic parameters that may be amplified in premenopausal women receiving estradiol suppression for breast cancer. Denosumab offsets deleterious skeletal effects of estradiol suppression and has been reported to have effects on body composition and metabolic parameters in pre-clinical and observational studies, though evidence from double-blind randomized controlled trials is limited.

Objective: To assess the effect of denosumab on body composition and metabolic parameters.

Methods: In a pre-specified secondary analysis of a 12-month randomized, double-blind, placebo-controlled trial, 68 premenopausal women with breast cancer initiating ovarian function suppression and aromatase inhibition were randomized to denosumab 60-mg or placebo administered at baseline and 6 months. Outcome measures were total and regional fat and lean mass (DXA), body mass index (BMI), waist and hip circumference, fasting glucose, HOMA-IR, and lipid profile. Using a mixed model, between-group mean adjusted differences, MAD, [95% confidence interval], over time are reported.

Results: Over 12 months, relative to placebo, android and gynoid fat mass decreased in the denosumab group (-266 g [95%CI -453 to -79], P = 0.02, and -452 g [95%CI -783 to -122], P = 0.03, respectively). Total fat mass and waist circumference were lower in the denosumab group but not significantly so (-1792g [95% CI -3346 to -240], P = 0.08 and (- 3.77 cm [95% CI -6.76 to -0.79], P = 0.06, respectively). No significant treatment effects were detected in lean mass, BMI, hip circumference, fasting glucose, HOMA-IR, or lipid profile.

Conclusions: In premenopausal women receiving estradiol suppression, denosumab decreases some measures of fat mass with no detectable effects on other measures of body composition or metabolic parameters.

Keywords: body composition; breast cancer; denosumab; estradiol suppression; glucose metabolism; lipids.