METABOLIC EFFECTS OF THIAZIDE AND 1,25-(OH)(2) VITAMIN-D IN POSTMENOPAUSAL OSTEOPOROSIS

It was previously shown that the stimulation of intestinal calcium abs orption by exogenous 25-hydroxyvitamin D (25-OHD) in postmenopausal wo men with osteoporosis was attenuated when thiazide was added, probably due to the suppression of endogenous synthesis of 1,25-(OH)2 vitamin D (1,25-(OH)2D). To test whether the above attenuation could be averte d if exogenous 1,25-(OH)2D replaced 25-OHD, 10 women with postmenopaus al osteoporosis participated in a three-phase study comprising control (pretreatment), treatment with 1,25-(OH)2D 0.5 mug/day for 4 weeks, a nd combined 1,25-(OH)2D and trichlormethiazide (TZ) 2 mg/day for 4 wee ks. The 1,25-(OH)2D treatment significantly increased serum 1,25-(OH)2 D from 60 +/- 7.2 (SD) to 154 +/- 48 pmol/l, fractional intestinal cal cium absorption (alpha) from 0.386 +/- 0.055 to 0.613 +/- 0.081, and u rinary calcium from 3.7 +/- 0.8 to 6.6 +/- 1.9 mmol/day. Addition of T Z significantly reduced urinary calcium from 6.6 +/- 1.9 to 4.8 +/- 1. 3 mmol/day, without changing alpha (0.613 +/- 0.081 to 0.584 +/- 0.070 ), serum calcium or 1,25-(OH)2D (154 +/- 48 to 154 +/- 38 pmol/l). Thu s, estimated calcium balance (absorbed minus urinary calcium, increase d marginally to +5.6 mmol/day on 1,25-(OH)2D alone (p = 0.028) and sig nificantly to +6.8 mmol/day on 1,25-(OH)2D+TZ, from the control value of +4.0 mmol/day. Seven patients who were treated long-term with combi ned 1,25-(OH)2D and TZ for 11-29 months maintained their alpha (0.593 +/-0.099) and a marginally more positive estimated calcium balance (+6 .4 mmol/day, p=0.025 from the control phase). Moreover, there was a st ability of bone density of radial shaft, femoral neck, and lumbar spin e. In conclusion, when exogenous 1,25-(OH)2D is provided, TZ does not lower serum 1,25-(OH)2D and alpha in patients with postmenopausal oste oporosis. Thus, the hypocalciuric action of TZ may lead to improved ca lcium balance and may potentially attenuate further bone loss.