Rejnmark L, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus, University Hospital, Aarhus, Denmark.
Eur J Clin Invest. 2001 Sep;31(9):764-72. doi: 10.1046/j.1365-2362.2001.00883.x.
Thiazide diuretics (TD) reduce urinary calcium, bone loss and fracture risk. Loop diuretics (LD) may have opposite effects. These effects could depend on induced rhythmic changes in bone and calcium homeostasis.
After a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms of plasma levels of calcium, phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D and osteocalcin, as well as renal excretions 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 bumetanide, n = 11), or placebo (n = 12).
In all four groups, all measured quantities showed a diurnal variation. LD caused a steep increase, with a subsequent decrease, in urinary calcium 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 group due to a rebound hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and osteocalcin were changed with an increase during daytime and a decrease during the night. TD did not alter the diurnal rhythm of any of the measured quantities. However, the 24-h renal calcium excretion decreased, whereas the mean 24-h plasma calcium concentration increased without PTH suppression. LD plus TD caused changes similar to those observed with LD alone.
One daily dose of LD increases parathyroid activity with alterations in the diurnal pattern of osteocalcin. This could indicate a potential anabolic effect of LD.
噻嗪类利尿剂（TD）可减少尿钙、骨质流失及骨折风险。袢利尿剂（LD）可能有相反作用。这些作用可能取决于骨骼和钙稳态中诱导的节律性变化。
在7天的导入期后，我们（采用析因设计）研究了50名绝经后女性血浆钙、磷、甲状旁腺激素（PTH）、1,25-二羟基维生素D和骨钙素水平的昼夜节律，以及钙、磷和1型胶原交联N端肽（NTx）的肾排泄率。这些女性被随机分为接受噻嗪类利尿剂（TD；苄氟噻嗪，n = 14）、袢利尿剂（LD；布美他尼，n = 13）、LD加TD（苄氟噻嗪加布美他尼，n = 11）或安慰剂（n = 12）治疗。
在所有四组中，所有测量量均呈现昼夜变化。LD导致尿钙和血浆PTH急剧升高，随后下降。与安慰剂组（4.4±0.4 mmol/L）相比，24小时血浆PTH平均浓度升高（8.5±0.9 mmol/L），而由于反弹性低钙尿，24小时净肾钙排泄与安慰剂组无差异。与安慰剂相比，血浆磷和骨钙素的昼夜节律发生改变，白天升高，夜间降低。TD未改变任何测量量的昼夜节律。然而，24小时肾钙排泄减少，而24小时血浆钙平均浓度升高，且无PTH抑制。LD加TD引起的变化与单独使用LD时观察到的变化相似。
每日一剂LD可增加甲状旁腺活性，并改变骨钙素的昼夜模式。这可能表明LD具有潜在的合成代谢作用。
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