Service of Nephrology, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.
J Clin Endocrinol Metab. 2011 Sep;96(9):E1482-5. doi: 10.1210/jc.2011-0373. Epub 2011 Jul 13.
Glitazones increase fracture risk in long-term users and in postmenopausal women. Studies have demonstrated deleterious effects of glitazones on bone metabolism. Glitazones also have direct renal tubular effects increasing sodium reabsorption. We hypothesized that glitazones may also regulate renal calcium excretion.
In this double-blind, randomized, placebo-controlled, four-way, crossover study, we examined the effects of pioglitazone (45 mg/d for 6 wk) or placebo on renal calcium and phosphate excretion and PTH levels during different sodium intakes in 16 individuals (eight with type 2 diabetes and eight with essential hypertension).
Pioglitazone had no effect on corrected plasma calcium and phosphate levels but decreased significantly the alkaline phosphatase and PTH levels. Pioglitazone induced on average a 45% increase in urinary calcium excretion. The fractional excretion of calcium rose to the same extent, suggesting a glomerular filtration rate-independent effect. Sodium intake did not influence the calciuric effect of pioglitazone. Changes in diurnal and nocturnal calciuria were similar. There was no effect of pioglitazone on phosphate excretion.
Pioglitazone decreases PTH levels and increases urinary calcium excretion, independently from changes in glomerular filtration rate and from the sodium load, suggesting an inhibitory effect of pioglitazone on the tubular reabsorption of calcium. These effects may contribute to the increased fracture risk with glitazone treatment.
吡格列酮会增加长期使用者和绝经后妇女的骨折风险。研究表明吡格列酮对骨代谢有不良影响。吡格列酮还具有直接的肾小管作用，增加钠的重吸收。我们假设吡格列酮也可能调节肾脏的钙排泄。
在这项双盲、随机、安慰剂对照、四向交叉研究中，我们检查了吡格列酮（45mg/d，持续 6 周）或安慰剂在不同钠摄入量下对 16 名个体（8 名 2 型糖尿病患者和 8 名原发性高血压患者）的肾脏钙和磷排泄以及甲状旁腺激素水平的影响。
吡格列酮对校正后的血浆钙和磷水平没有影响，但显著降低了碱性磷酸酶和甲状旁腺激素水平。吡格列酮平均使尿钙排泄增加 45%。钙的滤过分数增加到相同程度，提示肾小球滤过率独立的作用。钠摄入量不影响吡格列酮的排钙作用。昼夜尿钙排泄的变化相似。吡格列酮对磷排泄没有影响。
吡格列酮降低甲状旁腺激素水平并增加尿钙排泄，独立于肾小球滤过率的变化和钠负荷，提示吡格列酮抑制钙的肾小管重吸收。这些作用可能导致使用吡格列酮治疗时骨折风险增加。
