Messaggi chiave
- L’inibizione delle aromatasi (AI) associata a soppressione della funzione ovarica (OFS) migliora la sopravvivenza libera da malattia in pazienti in premenopausa con carcinoma mammario precoce (eBC) ER+, accelerando però la perdita ossea. Denosumab (DMAB) è un anticorpo monoclonale anti-RANKL che ha dimostrato di produrre una soppressione quasi completa del rimodellamento osseo AI-indotto nelle donne in postmenopausa.
- È stato condotto uno studio randomizzato, in doppio cieco, su DMAB rispetto a placebo in 68 donne in età premenopausale con eBC ER+ avviate ad AI + OFS. Nell’arco di 12 mesi, rispetto a placebo, DMAB ha prevenuto efficacemente e in modo statisticamente significativo la diminuzione della densità minerale ossea (BMD) (totale, corticale e trabecolare) a livello di tibia distale, come pure la rigidità stimata e il carico di rottura, con risultati simili per il radio distale. È stata inoltre prevenuta la riduzione della BMD a livello di rachide lombare, anca totale e collo femorale.
- Malgrado alcuni limiti, quali la breve durata del follow-up e le dimensioni limitate del campione, lo studio evidenzia come l’uso profilattico di DMAB sia in grado di preservare la BMD, la microarchitettura ossea e la forza stimata, con possibili effetti positivi sulla qualità della vita e sulla sopravvivenza libera da frattura.
Abstract
Purpose
- Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss.
- We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women.
Methods
- In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (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, and spine and hip BMD were measured using dual-energy X-ray absorptiometry at 0, 6, and 12 months.
- The primary end point and treatment effect was the mean adjusted between group difference (MAD; [95% CI]) in distal tibial total volumetric BMD over 12 months, with a single p value tested over all time points.
- The study is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; identifier: ACTRN12616001051437).
Results
- Intention-to-treat analysis included all 68 randomly assigned women.
- Over 12 months, compared with PBO, DMAB prevented the decrease in distal tibial total BMD (MAD, 20.8 mg HA/cm3 [95% CI, 17.3 to 24.2]), cortical BMD (42.9 mg HA/cm3 [95% CI, 32.1 to 53.9]), trabecular BMD (3.32 mg HA/cm3 [95% CI, 1.45 to 5.20], p = 0.004), estimated stiffness (11.6 kN/m [95% CI, 7.6 to 15.6]), and failure load (563 N [95% CI, 388 to 736]).
- Findings were similar at the distal radius.
- Decreases in BMD at the lumbar spine (MAD, 0.13 g/cm2 [95% CI, 0.11 to 0.15]), total hip (0.08 g/cm2 [95% CI, 0.07 to 0.09], and femoral neck (0.06 g/cm2 [95% CI, 0.05 to 0.07]) were also prevented.
- All p <0.001 unless otherwise noted.
Conclusions
- Treatment with DMAB at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.