Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemicalbone markers in postmenopausal women

Background Thiazide diuretics (TD) reduce urinary calcium, bone loss and fr acture risk. Loop diuretics (LD) may have opposite effects. These effects c ould depend on induced rhythmic changes in bone and calcium homeostasis. Design After a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms of plasma levels of calcium, phosphate, parathyroid hor mone (PTH), 1,25-dihydroxyvitamin D and osteocalcin, as well as renal excre tions rates of calcium, phosphate, and cross-linked N-terminal telopeptide of type 1 collagen (NTx) in 50 postmenopausal women randomized to treatment with either a thiazide diuretic (TD; bendroflumethiazide, n = 14), a loop diuretic (LD; bumetanide, n = 13), LD plus TD (bendroflumethiazide plus bum etanide, n = 11), or placebo (n = 12). Results In all four groups, all measured quantities showed a diurnal variat ion. LD caused a steep increase, with a subsequent decrease, in urinary cal cium and plasma PTH. The mean 24 h plasma PTH concentration was increased ( 8.5 +/- 0.9 mmol L-1) compared with placebo (4.4 +/- 0.4 mmol L-1), whereas net 24 h renal calcium excretion did not differ from that of the placebo g roup due to a rebound hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and osteocalcin were changed with an increase during d aytime and a decrease during the night. TD, did not alter the diurnal rhyth m of any of the measured quantities. However, the 24-h renal calcium excret ion decreased, whereas the 7 mean 24-h plasma calcium, concentration increa sed without PTH suppression. LD plus TD caused changes similar to those obs erved with LD alone. Conclusion One daily dose of LD increases parathyroid activity with a Itera tions in the diurnal pattern of osteocalcin. This could indicate a potentia l anabolic effect of LD.