title: Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Experts debate optimal 25-hydroxyvitamin D (25[OH]D) levels for musculoskeletal health.
  
  
  OBJECTIVE
  To compare the effects of placebo, low-dose cholecalciferol, and high-dose cholecalciferol on 1-year changes in total fractional calcium absorption, bone mineral density, Timed Up and Go and five sit-to-stand tests, and muscle mass in postmenopausal women with vitamin D insufficiency.
  
  
  METHODS
  This randomized, double-blind, placebo-controlled clinical trial was conducted at a single center in Madison, Wisconsin, from May 1, 2010, through July 31, 2013, and the final visit was completed on August 8, 2014. A total of 230 postmenopausal women 75 years or younger with baseline 25(OH)D levels of 14 through 27 ng/mL and no osteoporosis were studied.
  
  
  METHODS
  Three arms included daily white and twice monthly yellow placebo (n=76), daily 800 IU vitamin D3 and twice monthly yellow placebo (n=75), and daily white placebo and twice monthly 50,000 IU vitamin D3 (n=79). The high-dose vitamin D regimen achieved and maintained 25(OH)D levels≥30 ng/mL.
  
  
  METHODS
  Outcome measures were 1-year change in total fractional calcium absorption using 2 stable isotopes, bone mineral density and muscle mass using dual energy x-ray absorptiometry, Timed Up and Go and five sit-to-stand tests, functional status (Health Assessment Questionnaire), and physical activity (Physical Activity Scale for the Elderly), with Benjamini-Hochberg correction of P values to control for the false discovery rate.
  
  
  RESULTS
  After baseline absorption was controlled for, calcium absorption increased 1% (10 mg/d) in the high-dose arm but decreased 2% in the low-dose arm (P = .005 vs high-dose arm) and 1.3% in the placebo arm (P = .03 vs high-dose arm). We found no between-arm changes in spine, mean total-hip, mean femoral neck, or total-body bone mineral density, trabecular bone score, muscle mass, and Timed Up and Go or five sit-to-stand test scores. Likewise, we found no between-arm differences for numbers of falls, number of fallers, physical activity, or functional status.
  
  
  CONCLUSIONS
  High-dose cholecalciferol therapy increased calcium absorption, but the effect was small and did not translate into beneficial effects on bone mineral density, muscle function, muscle mass, or falls. We found no data to support experts' recommendations to maintain serum 25(OH)D levels of 30 ng/mL or higher in postmenopausal women. Instead, we found that low- and high-dose cholecalciferol were equivalent to placebo in their effects on bone and muscle outcomes in this cohort of postmenopausal women with 25(OH)D levels less than 30 ng/mL.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00933244.
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hansen
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison2Quality and Patient Safety Analysis, Saint Luke's Health System, Kansas City, Missouri.
authors.forename: R Erin
authors.initials: RE
authors.lastname: Johnson
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Kaitlin R
authors.initials: KR
authors.lastname: Chambers
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Johnson
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Christina C
authors.initials: CC
authors.lastname: Lemon
authors.affiliation: Department of Computing and Biometry, University of Wisconsin College of Agriculture and Life Sciences, Madison.
authors.forename: Tien Nguyen Thuy
authors.initials: TN
authors.lastname: Vo
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Sheeva
authors.initials: S
authors.lastname: Marvdashti
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D002132:Calcium Radioisotopes / Q000494:pharmacology; D002762:Cholecalciferol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010807:Physical Endurance / Q000187:drug effects; D017698:Postmenopause / Q000502:physiology*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D050071:Bone Density Conservation Agents; D002132:Calcium Radioisotopes; D019275:Radiopharmaceuticals; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D