In an Australian single-center trial reported in the Journal of Clinical Oncology, Ramchand et al found that denosumab prevented bone loss vs placebo in premenopausal women with estrogen receptor–positive breast cancer receiving estradiol suppression therapy.
Study Details
In the double-blind trial, 68 women from Austin Health, University of Melbourne, who were initiating ovarian function suppression (gonadotropin-releasing hormone analog or bilateral oophorectomy) and an aromatase inhibitor were randomly assigned between August 2016 and March 2020 to receive denosumab at 60 mg (n = 34) or placebo (n = 34) at 0 and 6 months. Volumetric bone mineral density (BMD), microarchitecture, and estimated bone strength of the distal tibia and distal radius were measured using high-resolution peripheral quantitative computed tomography; spine and hip BMD were measured using dual-energy X-ray absorptiometry. The primary outcome measure was mean adjusted between-group difference (MAD) in distal tibial total volumetric BMD over 12 months.
Key Findings
Over 12 months, compared with placebo, denosumab treatment prevented (P < .001 for all comparisons, except as noted) the decrease in distal tibial total BMD (MAD = 20.8 mg hydroxyapatite [HA]/cm3, 95% confidence interval [CI] = 17.3–24.2 mg HA/cm3), cortical BMD (MAD = 42.9 mg HA/cm3, 95% CI = 32.1–53.9 mg HA/cm3), trabecular BMD (MAD = 3.32 mg HA/cm3, 95% CI = 1.45–5.20 mg HA/cm3; P = .004), estimated stiffness (11.6 kiloNewtons [kN]/m, 95% CI = 7.6–15.6 kN/m), and failure load (563 Newtons, 95% CI = 388–736). Similar findings were made in the distal radius.
Denosumab treatment also prevented (all P < .001) decreases in BMD at the lumbar spine (MAD = 0.13 g/cm2, 95% CI = 0.11–0.15 g/cm2), total hip (MAD = 0.08 g/cm2, 95% CI = 0.07–0.09 g/cm2), and femoral neck (MAD = 0.06 g/cm2, 95% CI = 0.05–0.07 g/cm2).
No fragility fractures or serious adverse events related to treatment were reported. The most common adverse events of any grade included joint pain (21%), back pain (9%), and increased blood pressure (9%) in the denosumab group, and joint pain (41%), back pain (15%), and nonspecific limb pain (12%) in the placebo group. Adverse events led to treatment discontinuation in three patients (9%) in the denosumab group and two patients (6%) in the placebo group.
The investigators concluded, “Treatment with [denosumab] at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.”
Sabashini K. Ramchand, MBBS, BMedSci, FRACP, of the Department of Medicine, Austin Health, University of Melbourne, Parkville, Australia, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Health and Medical Research Council and others. For full disclosures of the study authors, visit ascopubs.org.
