title: Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial.
abstract: A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20-29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10-19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baseline musculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. arastell@dom.wustl.edu
authors.forename: Antonella L
authors.initials: AL
authors.lastname: Rastelli
authors.forename: Marie E
authors.initials: ME
authors.lastname: Taylor
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Reina
authors.initials: R
authors.lastname: Armamento-Villareal
authors.forename: Shohreh
authors.initials: S
authors.lastname: Jamalabadi-Majidi
authors.forename: Nicola
authors.initials: N
authors.lastname: Napoli
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
mesh_terms: D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000652:urine; D004872:Ergocalciferols / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D009570:Nitriles / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000097:blood; D014230:Triazoles / Q000009:adverse effects*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D009570:Nitriles; D010281:Parathyroid Hormone; D014230:Triazoles; D014807:Vitamin D; D000077384:Anastrozole; C104450:25-hydroxyvitamin D; D002118:Calcium