title: The C-3α Epimer of 25-Hydroxycholecalciferol from Endogenous and Exogenous Sources Supports Normal Growth and Bone Mineral Density in Weanling Rats.
abstract: The C-3α epimer of 25-hydroxycholecalciferol [3-epi-25(OH)D3] is elevated in infants.
  
  
  
  We tested whether increasing cholecalciferol intake results in a dose-response in plasma 3-epi-25(OH)D3We also examined bone and mineral metabolism in response to 3-epi-25(OH)D3treatment.
  
  
  
  Sprague Dawley rats (4 wk old) were randomly assigned (n = 6/group of each sex) to AIN-93G diets with cholecalciferol at 1 (control), 2, or 4 IU/g diet for objective 1 and to diets with 3-epi-25(OH)D3at 0.5 or 1 IU/g diet or 25-hydroxycholecalciferol [25(OH)D3] at 0.5 IU/g diet for objective 2 for 8 wk. Measurements at weeks 0, 4, and 8 included body weight and length, plasma vitamin D metabolites, bone biomarkers, and bone mineral density determined by using dual-energy X-ray absorptiometry. Lumbar vertebra 3 (L3) geometry and volumetric bone mineral density (vBMD) were measured using microcomputed tomography. Differences between groups were identified for males and females separately.
  
  
  
  Weight and food intake were not different between groups. Elevated plasma 3-epi-25(OH)D3was observed only in females in the 4 IU cholecalciferol/g diet group (mean ± SD: 24.7 ± 17.1 ng/mL), compared with the control group (5.3 ± 1.4 ng/mL; P = 0.001). By week 8, both male and female rats in the 3-epi-25(OH)D3groups had >87% greater plasma 3-epi-25(OH)D3concentrations relative to the 25(OH)D3reference group (P < 0.0001). At week 8 in males only, parathyroid hormone was significantly lower (P = 0.019) in both 3-epi-25(OH)D3groups than in the 25(OH)D3group, and L3 total vBMD was higher (P = 0.004) in the 0.5 IU 3-epi-25(OH)D3group than in the 25(OH)D3group.
  
  
  
  Endogenously generated 3-epi-25(OH)D3is more prominent in female than in male rats. Exogenous 3-epi-25(OH)D3was as effective as 25(OH)D3in supporting bone mineral accretion in both sexes. It thus appears that 3-epi-25(OH)D3has biological activity and should be further explored.
authors.affiliation: School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Marija
authors.initials: M
authors.lastname: Djekic-Ivankovic
authors.affiliation: School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Paula
authors.initials: P
authors.lastname: Lavery
authors.affiliation: School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Sherry
authors.initials: S
authors.lastname: Agellon
authors.affiliation: School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada hope.weiler@mcgill.ca.
authors.forename: Hope A
authors.initials: HA
authors.lastname: Weiler
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects*; D002112:Calcifediol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002112:Calcifediol
keywords: bone; dose-response; epimer; parathyroid hormone; vitamin D; weanling rats