The Generation of C-3α Epimer of 25-Hydroxyvitamin D and Its Biological Effects on Bone Mineral Density in Adult Rodents

• Published in: Calcified tissue international Vol. 96; no. 5; pp. 453 - 464
• Main Authors: Bianchini, Christina, Lavery, Paula, Agellon, Sherry, Weiler, Hope A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.05.2015
• Subjects: Absorptiometry, Photon; Animals; Biochemistry; Biomedical and Life Sciences; Bone Density - drug effects; Cell Biology; Dietary Supplements; Endocrinology; Female; Life Sciences; Male; Original Research; Orthopedics; Rats; Rats, Sprague-Dawley; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D - chemistry; Vitamin D - pharmacology; Bone; Vitamin D; Cholecalciferol; Rodents; 3-epi-25(OH)D
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-015-9973-9

The source and function of C-3α epimer of 25(OH)D (C-3 epimer) is unknown. The objectives were to (1) establish if increasing doses of vitamin D (VD) results in a proportionate dose–response in C-3 epimer; and (2) determine the biological response of bone to C-3 epimer treatment. Sprague Dawley rats (12 weeks, n  = 36 female, n  = 36 male) were randomized to control AIN93-M diet (1 IU VD 3 /g diet) or an experimental diet for 8 weeks containing VD 3 at 2 or 4 IU/g diet, C-3 epimer at 0.5 or 1 IU/g diet or 25(OH)D (0.5 IU/g diet). BW and food consumption were measured weekly. Blood was sampled at week 0, 4, and 8 for assessment of VD metabolites and bone metabolism biomarkers. DXA (week 0, 4, and 8) and in vivo micro CT (μCT) (week 0 and 8) were performed in vivo plus ex vivo μCT imaging and bone biomechanics. Dietary intake and anthropometry did not differ among diet groups. The dose–response of VD generated significantly elevated C-3 epimer only in females with concentrations of 4 IU VD diet group [mean 84.6 (62.5) nmol/L] exceeding control [mean 21.4 (18.5) nmol/L, p  = 0.005]. Both sexes in the 25(OH)D group did not show significant increases in C-3 epimer, whereas 0.5 and 1 IU epimer groups exceeded 100 nmol/L of C-3 epimer by 8 weeks. These data suggest C-3 epimer is endogenously generated with higher intakes of VD. Endogenous and exogenous C-3 epimer accumulates in serum without impact upon bone health outcomes in a healthy young adult model over 8 weeks.