Prochaska Megan, Taylor Eric, Vaidya Anand, Curhan Gary
Divisions of Renal Medicine and.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and.
Clin J Am Soc Nephrol. 2017 Aug 7;12(8):1284-1290. doi: 10.2215/CJN.01420217. Epub 2017 Jun 2.
Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use.
We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20).
Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion.
既往研究表明肾结石患者的骨密度较低，但尚无纵向研究评估骨密度低的个体发生肾结石的风险。随访时间短的小型研究报告称，使用双膦酸盐可使24小时尿钙排泄减少。我们研究了骨密度低和使用双膦酸盐的病史与新发肾结石风险以及与24小时钙排泄之间的关联。
设计、研究地点、参与者及测量方法：我们对护士健康研究II中的96,092名女性进行了前瞻性分析。我们使用Cox比例风险模型对年龄、体重指数、噻嗪类药物使用情况、液体摄入量、补充钙的使用情况和饮食因素进行校正。我们还对2294名参与者进行了横断面分析，使用多变量线性回归比较有和没有骨密度低病史的参与者之间的24小时尿钙排泄情况，以及在458名骨密度低的参与者中，使用和未使用双膦酸盐的参与者之间的24小时尿钙排泄情况。
在1,179,860人年的随访期间，我们共识别出2564例新发结石。与无骨密度低病史的参与者相比，有骨密度低病史的参与者发生肾结石的多变量校正相对风险为1.39（95%置信区间[95%CI]，1.20至1.62）。在骨密度低的参与者中，使用双膦酸盐的参与者发生肾结石的多变量校正相对风险为0.68（95%CI，0.48至0.98）。在对24小时尿钙排泄的横断面分析中，有骨密度低病史的参与者24小时钙的多变量校正平均差异高10mg/d（95%CI，1至19）。然而，在有骨密度低病史的参与者中，使用双膦酸盐与24小时钙之间无关联，24小时钙的多变量校正平均差异为-2mg/d（95%CI，-25至20）。
骨密度低是新发肾结石的独立危险因素，且与24小时尿钙排泄增加有关。在骨密度低的参与者中，使用双膦酸盐与新发肾结石风险较低有关，但与24小时尿钙排泄无独立关联。
