Reduction in intestinal calcium absorption by hydrochlorothiazide in postmenopausal osteoporosis

In six women with postmenopausal osteoporosis, most of whom responded to 50 micrograms/day 25-hydroxyvitamin D (25-OHD) therapy with a rise in intestinal calcium (Ca) absorption, 50 mg/day hydrochlorothiazide (TZ) were added to determine whether the resulting decline in urinary Ca would cause Ca retention in the skeleton. Urinary Ca decreased from 183 +/- 48 (SD) mg/day to 142 +/- 67 mg/day (P less than 0.05) when TZ was added. However, fractional Ca absorption also declined from 0.532 +/- 0.077 during 25-OHD treatment to 0.401 +/- 0.064 during combined 25-OHD and TZ therapy (P less than 0.0025). The above changes were accompanied by a significant decline in urinary cAMP from 4.29 +/- 1.64 to 3.19 +/- 1.44 mumol/g creatinine (P less than 0.05) and in serum 1,25-dihydroxyvitamin D from 41 +/- 14 to 22 +/- 11 pg/ml (P less than 0.01). The results suggest that TZ lowers urinary Ca, suppresses parathyroid function, inhibits 1,25-dihydroxyvitamin D synthesis, and thereby reduces intestinal Ca absorption. Thus, combined 25-OHD and TZ therapy probably does not improve Ca balance.