Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: Evidence of an age‐related intestinal resistance to 1,25‐dihydroxyvitamin D action

We studied the mechanism of impaired calcium absorption with aging in 51 healthy women whose ages ranged from 26 to 88 years. Serum concentrations of 1,25‐dihydroxyvitamin D [1,25‐(OH)₂D, mean of four measurements per subject] increased with age by 22% (P < 0.05) but, by split‐point analysis, plateaued or decreased slightly after age 65. In a subset of 20 subjects, [³H]1,25‐(OH)₂D₃ kinetic analysis showed that this increase with age resulted from both increased production and decreased metabolic clearance of 1,25‐(OH)₂D. Despite the increase in serum 1,25‐(OH)₂D concentration, true calcium absorption did not change with age. The expected inverse correlation between true fractional calcium absorption and dietary calcium intake, however, was easily demonstrated (r = 0.66, P < 0.001). Serum intact parathyroid hormone (PTH) increased with age by 35% (P < 0.02) and serum bone gla protein (BGP, osteocalcin) increased by 47% (P < 0.001); the increases in serum PTH and serum BGP were directly correlated (r = 0.32, P < 0.05). The data are consistent with the following hypothetical model: (1) intestinal resistance to 1,25‐(OH)₂D action accounts for the increase in serum 1,25‐(OH)₂D concentrations with aging with no change in true calcium absorption; (2) this results in a compensatory increase in PTH secretion and in 1,25‐(OH)₂D production that prevents true calcium absorption from decreasing; (3) the previously described defect in 25‐hydroxyvitamin D (25‐OHD) 1α‐hydroxylase activity in aging animals and humans acccounts for the leveling off in serum 1,25‐(OH)₂D concentration after age 65 years; and (4) the secondary hyperparathyroidism leads to increased bone turnover and thus contributes to age‐related bone loss.