Background   In premenopausal women with early oestrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition result in a precipitous decline in oestradiol production. The resulting unbalanced and rapid bone remodelling replaces older more mineralised bone with a smaller volume of less fully mineralised new bone. We hypothesised that these changes result in severe trabecular and cortical microstructural deterioration and reduced matrix mineralisation density.

Methods         This cross-sectional study included 27 premenopausal women, mean age 43.3 years (range 30.4 to 53.7) with early breast cancer (‘cases’) made oestradiol deficient for 17 months (range 6-120) by combined ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal controls and 35 healthy postmenopausal controls, mean age 62.6 years (range 60.2 to 65.5).  Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography. Cortical and trabecular microstructure were quantified using the StrAx1.0 algorithm.  

Results           Compared with premenopausal controls, cases had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume fraction (bone volume/tissue volume, BV/TV) due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher. Compared with postmenopausal controls 20 years older, cases had comparable or lower trabecular BV/TV and comparable cortical porosity. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower in cases than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar.

Conclusion     The longevity of premenopausal women with early breast cancer treated with endocrine therapy and the severe microstructural deterioration associated with oestradiol depletion provide a compelling rationale to investigate the efficacy of antiresorptive therapy given at the onset of oestradiol suppression.