Yergey, Alfred L.

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51–76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51–79 years). 2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P < 0.001). 3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r= 0.61, P < 0.01). 4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. 5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.

Abstract True calcium absorption can only be measured by the time-consuming and expensive metabolic balance method and is not predicted well by measuring the fractional absorption (FA) of radiocalcium from a fixed calcium carrier. We describe here a 1 day method for measuring the actual fraction of calcium absorbed from the habitual diet (true fractional calcium absorption, TFCA) using stable isotopes of calcium. Oral and intravenous isotopes were administered with each of the three daily meals, and then the ratio of the two isotopes in the urine was measured by mass spectroscopy. In 12 subjects, TFCA determined from stable Ca correlated well with TFCA measured by the balance method (r = 0.71, P < 0.01), and the mean values were not different (0.26 and 0.26). In contrast, no significant correlation was found between FA and TFCA. The weak relationship between FA and TFCA underscores the importance of tracing dietary calcium rather than a fixed calcium carrier in tests of calcium absorption. Using the new method, TFCA was inversely related to dietary calcium (r = −0.45, P < 0.05), demonstrating that it could detect physiological changes in calcium absorption. Thus, this test has two important advantages: (1) it provides a simple way to measure TFCA and true fractional calcium absorption (the product of TFCA and dietary calcium), the physiologically relevant variables, and (2) because there is no radiation exposure, the test can be used in pregnant women and children, the isotopes can be prepared in advance, and several isotopes can be used simultaneously.

Abstract 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.