De Vecchis Renato, Ariano Carmelina, Di Biase Giuseppina, Noutsias Michel
Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", via Cagnazzi 29, 80137 Napoli, Italy.
Division of Cardiology, Casa di Cura "Sollievo della Sofferenza", viale Cappuccini 2, 71013 San Giovanni Rotondo, Italy.
J Clin Med Res. 2017 Nov;9(11):943-949. doi: 10.14740/jocmr3193w. Epub 2017 Oct 2.
An alleged association of chronic use of thiazide diuretics with an increased risk of bone fragility fractures has been highlighted by a relatively recent prospective cohort study. However, the concept that thiazides exert a beneficial effect on osteoporosis is still a predominant view. This effect would be mediated by the decrease in renal clearance of calcium ions, a pharmacological feature recognized for a long time now to this class of drugs, as opposed to the increase in calcium urinary excretion attributed instead to loop diuretics, i.e. furosemide and similar drugs. The purpose of this retrospective study was to attempt to clarify whether regular use of thiazide diuretics as antihypertensive therapeutics is associated with a significantly increased risk of osteoporotic fractures in female patients aged 65 or over.
In this two-center retrospective study, we followed up a cohort of female patients with (n = 80) and without (n = 158) thiazide-induced hyponatremia.
A total of 48 osteoporotic fractures were recorded during a median follow-up period of 57.5 months. By means of univariate regression analysis, an association was found between thiazide-induced hyponatremia and increased risk of vertebral fractures (odds ratio (OR): 7.6; 95% confidence interval (CI): 3.755 - 15.39; P < 0.0001). Multivariate regression analysis, however, showed that age (OR: 1.823; 95% CI: 1.211 - 2.743) and body mass index (OR: 0.156; 95% CI: 0.038 - 0.645) were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatremia and risk of fracture was noticeable in the final model.
Because thiazide-induced hyponatremia was associated with spinal fractures in univariate but not multivariate analysis, a possible explanation is that hyponatremia may be a confounder of the relation between body mass and spinal fractures. Indeed, reduced body mass especially among elderly women with small body build may confer heightened risk of thiazide-induced hyponatremia because of decreased bone sodium available for exchange with the serum sodium. Thus, occurrence of hyponatremia could only serve as an indirect surrogate marker for osteoporosis risk.
最近一项前瞻性队列研究强调了长期使用噻嗪类利尿剂与骨脆性骨折风险增加之间所谓的关联。然而，噻嗪类药物对骨质疏松症具有有益作用这一观点仍然占主导地位。这种作用是由钙离子肾清除率降低介导的，这是这类药物长期以来公认的药理学特征，与之相反，袢利尿剂（即呋塞米及类似药物）会导致尿钙排泄增加。这项回顾性研究的目的是试图阐明，将噻嗪类利尿剂作为抗高血压药物常规使用，是否会使65岁及以上女性患者骨质疏松性骨折的风险显著增加。
在这项双中心回顾性研究中，我们对一组有（n = 80）和无（n = 158）噻嗪类药物引起的低钠血症的女性患者进行了随访。
在中位随访期57.5个月期间，共记录到48例骨质疏松性骨折。通过单因素回归分析，发现噻嗪类药物引起的低钠血症与椎体骨折风险增加之间存在关联（比值比（OR）：7.6；95%置信区间（CI）：3.755 - 15.39；P < 0.0001）。然而，多因素回归分析表明，年龄（OR：1.823；95% CI：1.211 - 2.743）和体重指数（OR：0.156；95% CI：0.038 - 0.645）是骨质疏松性骨折仅有的独立预测因素。在最终模型中，未发现噻嗪类药物引起的低钠血症病史与骨折风险之间存在关联。
由于噻嗪类药物引起的低钠血症在单因素分析中与脊柱骨折相关，而在多因素分析中不相关，一个可能的解释是低钠血症可能是体重与脊柱骨折之间关系的一个混杂因素。事实上，体重减轻，尤其是身材矮小的老年女性，可能会因可用于与血清钠交换的骨钠减少而增加噻嗪类药物引起低钠血症的风险。因此，低钠血症的发生只能作为骨质疏松症风险的一个间接替代指标。
