A defect in renal calcium conservation may contribute to the pathogenesis of postmenopausal osteoporosis

Although all postmenopausal women are estrogen deficient, women who have postmenopausal osteoporosis may have a defect, in addition to estrogen deficiency, that accounts for their higher rates of bone resorption and greater bone loss, relative to those who do not. To test the hypothesis that one defect is an impairment in renal calcium conservation, we measured renal calcium transport in 19 osteoporotic and 19 normal postmenopausal women, whose ages (median and 25th-75th percentile range) were 70 yr (range, 67-72) and 72 yr (range, 69-74), respectively. There was no difference between groups in values for serum ionized calcium and PTH concentrations or in renal filtered load of calcium. However, before PTH infusion, the osteoporotic women had lower (P = 0.0046) values for tubular reabsorption of calcium (TRCa) of 96.8% (range, 96.0-97.1) vs. 98.0% (range, 97.2-98.3) and higher (P = 0.0154) urinary calcium excretion of 0.194 mg/dL of glomerular filtrate (GF) (0.154-0.239) vs. 0.125 mg/dL of GF (0.103-0.173) than the normal women. After infusion of 200 U of synthetic PTH (synthetic 1-34 analog of human PTH), TRCa increased and calcium excretion decreased comparably in both groups, so that the differences between groups after intervention remained: for TRCa, 98.3% (97.7-98.6) vs. 98.9% (98.4-99.3; P = 0.0042); and for calcium excretion, 0.099 mg/dL of GF (0.080-0.138) vs. 0.066 mg/dL of GF, (0.045-0.097, P = 0.0180). In conclusion, postmenopausal women with osteoporosis have a PTH-independent defect in renal calcium conservation. This defect is of sufficient magnitude to contribute to the greater negative calcium balance in postmenopausal women with osteoporosis vs. their postmenopausal peers.