Transbøl I, Christensen M S, Jensen G F, Christiansen C, McNair P
Metabolism. 1982 Apr;31(4):383-6. doi: 10.1016/0026-0495(82)90115-9.
The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.
在一项为期3年的安慰剂对照临床试验中,研究了噻嗪类药物对正常绝经后妇女骨矿物质流失的影响。63名处于绝经早期的健康女性被随机分为两组,一组每天服用5毫克苄氟噻嗪进行治疗,另一组服用安慰剂,为期2年,而在试验的第三年两组均服用安慰剂。在整个36个月期间,所有参与者每天都补充0.5克钙。通过对前臂进行125I光子吸收测定法测定的骨矿物质含量(BMC),安慰剂组每年下降2%(p<0.001)。在噻嗪类药物组中,最初6个月内BMC未见下降,此后BMC以与安慰剂组相同的速率下降。在3年试验结束时,安慰剂组的BMC平均为94.1%,噻嗪类药物组为95.2%(p>0.05)。尽管每天补充0.5克钙,噻嗪类药物仍使尿钙排泄持续下降25%(p<0.001),而安慰剂组的钙补充剂使平均尿钙显著增加10%-20%(p<0.001)。停用噻嗪类药物后出现反弹效应,导致尿钙显著升高。停用钙补充剂1个月后,两组的尿钙排泄均恢复到初始水平。结论是,尽管噻嗪类药物有持续降低尿钙的作用,但对绝经后骨质流失的影响是短暂的。