The Generation of C-3[alpha] 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; p. 453
• Main Authors: Bianchini, Christina, Lavery, Paula, Agellon, Sherry, Weiler, Hope A
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01.05.2015
• Subjects: Bone density; Nutrition; Rodents; Vitamin D
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/s00223-015-9973-9

The source and function of C-3[alpha] 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^sub 3^/g diet) or an experimental diet for 8 weeks containing VD^sub 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 ([mu]CT) (week 0 and 8) were performed in vivo plus ex vivo [mu]CT 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.