Metabolic effects of thiazide and 1,25-(OH)2 vitamin D in postmenopausal osteoporosis

Abstract

It was previously shown that the stimulation of intestinal calcium absorption by exogenous 25-hydroxyvitamin D (25-OHD) in postmenopausal women 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 averted if exogenous 1,25-(OH)2D replaced 25-OHD, 10 women with postmenopausal osteoporosis participated in a three-phase study comprising control (pretreatment), treatment with 1,25-(OH)2D 0.5 microgram/day for 4 weeks, and combined 1,25-(OH)2D and trichlormethiazide (TZ) 2 mg/day for 4 weeks. The 1,25-(OH)2D treatment significantly increased serum 1,25-(OH)2D from 60 +/- 7.2 (SD) to 154 +/- 48 pmol/l, fractional intestinal calcium absorption (alpha) from 0.386 +/- 0.055 to 0.613 +/- 0.081, and urinary calcium from 3.7 +/- 0.8 to 6.6 +/- 1.9 mmol/day. Addition of TZ 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). Thus, estimated calcium balance (absorbed minus urinary calcium, increased marginally to +5.6 mmol/day on 1,25-(OH)2D alone (p = 0.028) and significantly 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 combined 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 stability of bone density of radial shaft, femoral neck, and lumbar spine.(ABSTRACT TRUNCATED AT 250 WORDS)