A phase II RCT of high-dose vitamin D supplementation and exercise for cancer treatment-induced bone loss in breast cancer patients on aromatase inhibitors.

Abstract

11500 Background: Cancer-treatment-induced bone loss (CTIBL) is a side effect of aromatase inhibitors (AIs) and can result in osteoporotic fractures. Vitamin D (VITD) protects against postmenopausal bone loss but it is unclear if the recommended daily allowance (RDA: 600 IU/day) of VITD is sufficient to prevent CTIBL. This phase II RCT aimed to assess the feasibility, safety, and preliminary efficacy of high-dose VITD (with and without exercise) on bone mineral density (BMD) compared to the RDA. Methods: Non-metastatic breast cancer patients starting AIs with low VITD (<32 ng/ml) were randomized 1:1:1 into 3 arms: 1) placebo 2) high-dose VITD (50,000 IU/week) or 3) high-dose VITD + Exercise for Cancer Patients (EXCAP): a home-based, personalized walking and resistance band training program for 24 weeks. All subjects received the RDA of VITD 600 IU/day. Serum VITD and calcium levels were assessed at baseline, weeks 6, 12, 18, and 24. BMD was assessed at the hip via DXA at baseline and week 24. Results: Of the 116 subjects randomized (mean age = 60; 94% white; mean baseline VITD = 24.6 ng/mL), 90 provided fully evaluable data. Compliance (≥ 80% of instructed doses) exceeded 95% in all 3 arms with no between-group difference. ANCOVA showed significant differences between groups on final VITD levels (high-dose = 63.6 vs high-dose + EXCAP = 60.3 vs placebo = 32.0 ng/mL; p<0.001) without severe calcium toxicities, as indicated by final calcium level (high-dose = 9.4 vs high-dose + EXCAP = 9.5 vs placebo = 9.4 ng/mL; p = 0.78). The placebo group lost a significant amount of hip BMD (−1.7%; p < 0.01) while hip BMD was maintained in the high-dose (−0.1%; p = 0.77) and high-dose + EXCAP (−0.2%; p = 0.74) resulting in significant between-group differences for high-dose + EXCAP vs placebo (p = 0.04) and high-dose vs placebo (p = 0.05). Conclusions: This is one of the first studies to show our novel high-dose VITD intervention, with and without exercise, significantly reduced hip BMD loss in breast cancer patients on AIs. Moreover, high-dose VITD supplementation is safe and feasible in this population. A phase III RCT is needed to confirm these findings. Funding: K07CA168911. Clinical trial information: NCT01419730.