Thiazides and seasonal bone change in healthy postmenopausal women

Abstract

Thiazide diuretic use has been associated with reduced rates of bone loss and bone density has been found to fluctuate with time of year. Here we examine associations between thiazide use, calcium regulating hormones, and the pattern of bone change during the 6-month intervals of summer/fall when bone density increases and winter/spring when bone density declines. Of the 246 postmenopausal women who completed a 1-year calcium and vitamin D supplement trial, 25 used a thiazide diuretic. In the winter/spring, bone loss was reduced in the thiazide users (for L2-4: 0.46 +/- 0.59 (SE)% for thiazide users vs. -1.02 +/- 0.17% for non-users, P = 0.017; for whole-body: -0.13 +/- 0.25% vs. -0.67 +/- 0.08, P = 0.043). The benefit at the whole body was dose related. Increases in bone density were similar in the two groups in the summer/fall. Associations between thiazide use and net spinal change and between thiazide dose and net whole-body bone change were positive. Thiazide users had lower serum levels of PTH (26.2 +/- 7.6 (SD) ng/l vs. 31.0 +/- 11.7 ng/l, P = 0.009) and 1,25-dihydroxyvitamin D (60.8 +/- 16.2 pmol/l vs. 77.0 +/- 18.7 pmol/l, P < 0.001) in the winter/spring and, in the subset measured, reduced levels of osteocalcin year round (summer/fall: 2.89 +/- 0.82 micrograms/l, n = 10, vs. 3.65 +/- 1.02, n = 82, P = 0.019; winter/spring: 2.54 +/- 0.80 micrograms/l vs. 3.47 +/- 1.07 micrograms/l, P = 0.005). Sodium excretion in the two groups did not differ in the winter/spring. In conclusion, beneficial bone effects of thiazide diuretics occur in the winter/spring and they may result from a decrease in PTH-stimulated bone resorption and an associated reduction in the bone turnover rate.