Intestinal calium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P <0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P <0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH) 2D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH) 2D were positively correlated (r = 0.50, P <0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P <0.01) and with serum 1,25(OH) 2D (r= -0.5, P <0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH) 2D was significantly decreased in both osteoporotic patients and elderly normals (P <0.001). In osteoporotic patients, calcium absorption increased significantly (P <0.001) after 7 d administration of a small dose (0.4 μg/d) of synthetic 1,25(OH) 2D 3. In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH 2-terminal assay) relative to age-matched controls, and mean serum phosphate was increased. The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH) 2D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH) 2D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH) 2D, analagous to that seen in aging rats, cannot be excluded.
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