Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels in young versus elderly women: Evidence for age-related intestinal resistance to 1,25(OH)(2)D action

Intestinal calcium absorption decreases with aging, but it is unclear wheth er this is attributable to an age-related intestinal resistance to 1,25-dih ydroxyvitamin D [1,25(OH)(2)D] action. Thus, we assessed the in vivo dose r esponse of active intestinal calcium absorption to a broad range of circula ting 1,25(OH)(2)D 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, s uppressing 1,25(OH)(2)D levels; group 2 was even a normal calcium diet of 1 5-30 mmol/day, representing basal 1,25(OH)(2)D levels; group 3 was given a low-calcium diet of 5 mmol/day to stimulate endogenous 1,25(OH)(2)D product ion; group 4 was given the low-calcium diet plus 1 mug/day 1,25(OH)(2)D; an d group 5 was given a low-calcium diet plus 2 mug/day 1,25(OH)(2)D. After 7 days of diet and/or 1,25(OH)(2)D treatment, fasting fractional calcium abs orption (FCA) was assessed by a double-tracer method using stable calcium i sotopes. Serum 1,25(OH)(2)D and vitamin D-binding protein levels were measu red concurrently, and the free 1,25(OH)(2)D index [molar ratio of 1,25(OH)( 2)D to DBP] was calculated. FCA was significantly correlated with the free 1,25(OH)(2)D index in the yo ung (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)(2)D index (representing intestinal sensitivity to 1,25(OH)(2)D) was significan tly 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)(2)D levels, we demonstrate that elderly women have a resistance to 1,2 5(OH)(2)D action that may contribute to their negative calcium balance, sec ondary hyperparathyroidism, and bone loss.