Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in young versus elderly women: evidence for age-related intestinal resistance to 1,25(OH)2D action.
Intestinal calcium absorption decreases with aging, but it is unclear whether this is attributable to an age-related intestinal resistance to 1,25-dihydroxyvitamin D [1,25(OH)2D] action. Thus, we assessed the in vivo dose response of active intestinal calcium absorption to a broad range of circulating 1,25(OH)2D levels in elderly [age (mean +/- SD), 72.5+/-3.0 yr] vs. young women (age, 28.7+/-5.3 yr; n = 20 per group), who were stratified into 5 subgroups: group 1 was given a high calcium intake of 75 mmol/day, suppressing 1,25(OH)2D levels; group 2 was given a normal calcium diet of 15-30 mmol/day, representing basal 1,25(OH)2D levels; group 3 was given a low-calcium diet of 5 mmol/day to stimulate endogenous 1,25(OH)2D production; group 4 was given the low-calcium diet plus 1 microg/day 1,25(OH)2D; and group 5 was given a low-calcium diet plus 2 microg/day 1,25(OH)2D. After 7 days of diet and/or 1,25(OH)2D treatment, fasting fractional calcium absorption (FCA) was assessed by a double-tracer method using stable calcium isotopes. Serum 1,25(OH)2D and vitamin D-binding protein levels were measured concurrently, and the free 1,25(OH)2D index [molar ratio of 1,25(OH)2D to DBP] was calculated. FCA was significantly correlated with the free 1,25(OH)2D index in the young (R = 0.63, P = 0.003) but not in the elderly women (R = 0.27, P = 0.25). Moreover, the slope of the relationship between FCA and free 1,25(OH)2D index (representing intestinal sensitivity to 1,25(OH)2D) was significantly greater in the young (compared with the elderly) women [mean +/- SEM, 0.15+/-0.04 (young) vs. 0.03+/-0.02, elderly, P = 0.03]. Thus, using an experimental design that allowed us to assess FCA over a wide range of 1,25(OH)2D levels, we demonstrate that elderly women have a resistance to 1,25(OH)2D action that may contribute to their negative calcium balance, secondary hyperparathyroidism, and bone loss.
Pattanaungkul
S
S
Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Riggs
B L
BL
Yergey
A L
AL
Vieira
N E
NE
O'Fallon
W M
WM
Khosla
S
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000493:pharmacokinetics*; D002136:Calcium, Dietary; D005215:Fasting; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D012044:Regression Analysis
D002136:Calcium, Dietary; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium