High-dose vitamin D2 (HDD) supplementation improved aromatase-induced musculoskeletal symptoms (AIMSS) and bone loss in women with early breast cancer taking adjuvant anastrozole in a randomized phase II trial.

Aromatase inhibitors, which are commonly prescribed to shrink estrogen-fueled breast tumors and prevent their recurrence, are less toxic than chemotherapy but cause severe musculoskeletal discomfort in approximately 50% of patients, including pain and stiffness in the hands, wrists, knees, hips, lower back, shoulders, and feet. After noticing that patients who experienced these problems found some relief with high doses of vitamin D, a team of researchers studied the effects of HDD supplementation in 60 women with early breast cancer and AIMSS brought on by adjuvant anastrozole therapy. 

Women with a baseline 25-hydroxy vitamin D (25OHD) level of 20 to 29 ng/mL received HDD capsules of 50,000 IU each week for 8 weeks and then monthly for 4 months, or placebo. Women with 25OHD levels of 10 to 19 ng/mL received HDD for 16 weeks and then monthly for 2 months, or placebo. Baseline characteristics were comparable between the groups.


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Bone mineral density (BMD) was measured at baseline and 6 months, and other health questionnaires were used to assess measures of discomfort at 2, 4, and 6 months. The researchers noted the following:

  • At the 2-month mark, pain scores improved more in the HDD groups than in the placebo groups.
  • The positive effect of HDD on AIMSS was stronger across all time points in the women who had the lower vitamin D levels at baseline.
  • Bone mineral density in the femoral neck decreased in the placebo users and did not change in the HDD patients.

“Weekly HDD improves AIMSS and may have a positive effect on bone health,” affirmed the researchers in their report for Breast Cancer Research and Treatment (2011;129[1]:107-116). “Vitamin D supplementation strategies for breast cancer patients on [aromatase inhibitor therapy] should be further investigated.”