The C-30α Epimer of 25-Hydroxycholecalciferol from Endogenous and Exogenous Sources Supports Normal Growth and Bone Mineral Density in Weanling Rats

Background: The C-3 alpha epimer of 25-hydroxycholecalciferol [3-epi-25(OH)D3] is elevated in infants. Objectives: We tested whether increasing cholecalciferol intake results in a dose-response in plasma 3-epi-25(OH)D-3. We also examined bone and mineral metabolism in response to 3-epi-25(OH)D-3 treatment. Methods: Sprague Dawley rats (14 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)D-3 at 0.5 or 1 IU/g diet or 25-hydroxycholecalciferol [25(OH)D-3] 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. Results: Weight and food intake were not different between groups. Elevated plasma 3-epi-25(OH)D-3 was 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)D-3 groups had >87% greater plasma 3-epi-25(OH)D-3 concentrations relative to the 25(OH)D-3 reference group (P < 0.0001). At week 8 in males only, parathyroid hormone was significantly lower (P= 0.019) in both 3-epi-25(OH)D-3 groups than in the 25(OH)D-3 group, and L3 total vBMD was higher (P = 0.004) in the 0.5 IU 3-epi-25(OH)D-3 group than in the 25(OH)D-3 group. Conclusions: Endogenously generated 3-epi-25(OH)D-3 is more prominent in female than in male rats. Exogenous 3-epi-25(OH)D-3 was as effective as 25(OH)D-3 in supporting bone mineral accretion in both sexes. It thus appears that 3-epi-25(OH)D-3 has biological activity and should be further explored.