Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis.

We investigated the parathyroid hormone-1,25-dihydroxyvitamin D3 (1,25(OH)2D) axis in osteoporosis by administering phosphate to 8 postmenopausal women with osteoporosis (49 to 78 years old) and to 10 normal women matched for age (50 to 74 years). All subjects responded with a similar increase in the serum phosphorus concentration (women with osteoporosis, 1.15 +/- 0.06 to 1.79 +/- 0.09 mmol per liter; controls, 1.14 +/- 0.05 to 1.73 +/- 0.08 mmol per liter) and a fall in the ionized calcium concentration (women with osteoporosis, 1.12 +/- 0.03 to 1.06 +/- 0.03 mmol per liter; controls, 1.17 +/- 0.01 to 1.11 +/- 0.02 mmol per liter). Parathyroid hormone levels rose 2.5-fold in the control group (15.4 +/- 2.2 to 37.9 +/- 6.1 pg per milliliter) but increased by only 43 percent in the group with osteoporosis (14.8 +/- 2.8 to 21.2 +/- 4.1 pg per milliliter), an increase similar to that previously reported in young normal subjects (53 percent). In healthy older and younger subjects, the levels of 1,25(OH)2D did not change; in the subjects with osteoporosis, however, they decreased significantly (50 percent). We conclude that older women require a greater parathyroid hormone stimulus than younger women to maintain vitamin D homeostasis, because of an age-related decline in the formation of 1,25(OH)2D in response to parathyroid hormone, and that in osteoporosis the age-appropriate parathyroid hormone response to the same hypocalcemic signal is diminished. Our results are consistent with the presence of an abnormality in parathyroid hormone secretory function in osteoporosis in addition to the universal decline in 1,25(OH)2D responsiveness associated with aging.