A Double-Blind, Randomized, Placebo-Controlled Trial of High Dose Vitamin D Therapy on Musculoskeletal Pain and Bone Mineral Density in Anastrozole-Treated Breast Cancer Patients with Marginal Vitamin D Status.
Authors: Rastelli A. , Taylor M. , Villareal R. , Jamalabadi-Majidi S. , Gao F. , Ellis M. 
Published: December 2010

Abstract
Rationale: Musculoskeletal (MS)pain is a known adverse class effect of aromatase inhibitors. Previously we reported high prevalence of Vitamin D deficiency in breast cancer patients complaining of MS pain, and anecdotal improvement of MS pain with weekly supplementation of high dose Vitamin D (HDD) (1). Here we report on a randomized double-blind, placebo-controlled trial of weekly HDD (ergocalciferol 50,000 IU) versus placebo (PBO) in breast cancer patient receiving anastrozole, with new or worsening MS pain since initiation of treatment, and with marginal levels of 25-OH Vitamin D (25OHD). The secondary aim was to determine whether HDD supplementation protects from bone loss.Methods: Inclusion criteria: 1) Postmenopausal women with invasive breast cancer (stage I - IIIB) on Anastrozole for at least 8 weeks; 2) new or worsening MS pain; 3) serum 25OHD level between 10 and 29 ng/ml. Design: 2 strata: 1) if 25OHD levels between 20-29 ng/ml, patients received 8 weeks of HDD then monthly HDD until the end of study (6 months) or PBO; 2) if 25OHD levels between 10-19 ng/ml, patients received 16 weeks HDD followed by monthly HDD until the end of the study or PBO. In addition, all patients received calcium (1000 mg/day) and standard Vitamin D supplementation (400 IU/day). Pain was measured by validated questionnaires (BPI, HAQ, FIQ) at baseline, month 2, month 4 and month 6. Bone Mineral Density was measured at baseline and at 6 months using a Hologic densitometer.Results: Sixty patients were enrolled. Mean age was 61.5 years. HDD and PBO groups did not differ at baseline in pain scores and 25OHD levels.At 2 months the HDD group reported lower scores on pain-related questions on BPI (question #3) at 2 mo, p=0.01 and FIQ (question #15), at 2 mo p=0.02. There was also a trend for better scores for walking and climbing steps on the HAQ [Group x Time Chi-square=3.6; at 2 mo p=0.02; p=0.009 at 4 mo]. Preliminary analysis of bone density data show higher femoral neck values in the HDD group at 6 months [% change 0-6 mo: HDD=0.54±0.71, PBO= -1.43±0.66, p=0.05]. There were no significant toxicities.Conclusions: HDD is well tolerated in this study, improves MS pain in patients receiving anastrozole, and may help functional activity. The effect was limited to the 2 month interval when patients on the active arm were receiving weekly treatment. Improvements decreased at 4 and 6 months once patients switched to monthly supplements. HDD may have also a positive effect on bone health. Limits of this pilot randomized study include the small number of patients, and the difficulty of measuring pain using clinical questionnaires.1) Taylor ME, Rastelli A, et.al. Incidence of 25-OH vitamin D deficiency in patients with a history of breast cancer who have musculoskeletal symptomatology. San Antonio Breast Cancer Symposium, Poster # 3072, December 2004Supported by Astra-Zeneca
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 803.