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

Abstract

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 preclinical and observational studies, but 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 prespecified 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 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 = .02, and −452 g [−783 to −122], P = .03, respectively). Total fat mass and waist circumference were lower in the denosumab group but not significantly (−1792 g [−3346 to −240], P = .08 and (− 3.77 cm [−6.76 to −0.79], P = .06, respectively). No significant treatment effects were detected in lean mass, BMI, hip circumference, fasting glucose, HOMA-IR, or lipid profile. Conclusion 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.