Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS)

Abstract

Purpose To evaluate the efficacy and safety of vitamin D3 at 4,000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. Methods Single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stage I-IIIA breast cancer, taking AI and experiencing AIMSS (Breast Cancer Prevention Trial Symptom Scale-Musculoskeletal Subscale ≥1.5 (BCPT-MS)) were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n=56) or 4,000 IU D3 (n=57) daily for 6 months. The primary endpoint was change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general musculoskeletal pain; joint pain; muscle stiffness; range for each question: 0=not at all to 4=extremely). Results Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. Conclusions We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).

Management of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis

“…Out of 17 RCTs, only 11 could be adequately assessed for methodological quality, as the rest were only published in abstract form. Of the 11 assessable RCTs, eight studies had a high Jadad score ≥3 (26)(27)(28)(29)(30)(31)(32)(33). Three studies scored poorly on the Jadad scale for methodological quality (34)(35)(36).…”

Integrative medicine in cancer survivors

“…AIMSS was scored using the breast cancer prevention symptom scales-MS subscale. The scores were similar in the two groups (2.3 vs. 2.4) with no significant difference in score change after 6 months (2.0 vs. 1.9) [34]. These small studies of Vitamin D supplementation in cancer survivors should be seen only as hypothesis-generating given the confounding factors and that prior large RCTs have shown harm instead of benefit of single-substance supplementation [35].…”

Pain in cancer survivors; filling in the gaps

“…133 However a randomised trial looking at high and low doses of vitamin D supplementation did not show any significant differences in the incidence of AIA. 134 Imaging techniques may give insight not only into diagnosis but also aetiology. A relatively robust finding on ultrasound and MRI is the observation of fluid and frequent thickening in tendon sheaths.…”