Increased bone mineral density in a population-based group of 70-year-old women on thiazide diuretics, independent of parathyroid hormone levels

Background. Several studies have shown greater bone mineral density (BMD) in people receiving thiazide diuretics compared with controls. Most researchers have related this association to the hypocalciuric effect of thiazides with subsequent rise in serum calcium and fall in parathyroid hormone (PTH) levels. Recent experimental evidence suggests, however, a direct effect of thiazides on osteoblast-like cells. Objective. To test the hypothesis that the association of thiazides and raised BMD is independent of PTH levels in humans. Subjects. A population-based group of 248 70-year-old Icelandic women, 51 receiving thiazide diuretics. 39 receiving other antihypertensive therapy and the rest acting as controls. Main outcome measures. The independent contribution of thiazide usage and PTH to BMD in a multivariate analysis. Results. The mean BMD was 9.6% greater in the lumbar spine (P < 0.01) and 5.4%, greater in the whole skeleton (P < 0.01) amongst thiazide users than in controls, reduced to 7.6%, (P < 0.02) and 4.5% (P < 0.01), respectively, when corrected for fat mass which was 5.8 kg greater in the thiazide group. In a multivariate analysis, corrected for body weight and body composition, serum calcium and In-PTH, thiazides remained a significant independent predictor of BMD in the total skeleton and lumbar spine, but not in the total hip or femoral neck. Thiazides explained about 3% of the variability in whole body and lumbar spine BMD. Conclusions. Thiazides augment or preserve BMD independent of PTH, implying other mechanisms.