Vouri Scott Martin, Alvarez Carlos A, Blaszczyk Amie Taggart
Saint Louis College of Pharmacy, St. Louis, Missouri, USA.
Am J Geriatr Pharmacother. 2012 Jun;10(3):178-84. doi: 10.1016/j.amjopharm.2012.04.001. Epub 2012 Apr 27.
Limited data exist on the use of bisphosphonates in patients with poor kidney function due to a contraindication derived from inadequate experience among patients with kidney failure, accounting for as much as 25% of nonprescribing when otherwise appropriate.
To determine whether bisphosphonate use in patients with decreased renal function, as outlined in the package insert (estimated creatinine clearance [eCrCl] <35 mL/min), would result in higher rates of hypocalcemia, as suggested in previous studies.
This was a retrospective cohort study of elderly veterans 65 years of age and older at the Veterans Affairs North Texas Health Care System in Dallas, Texas. We identified 3089 patients who started oral bisphosphonate therapy between August 1, 2003 and July 12, 2010. Of the 252 patients meeting the inclusion criteria, 25 and 227 patients had an eCrCl <35 mL/min and eCrCl ≥35 mL/min, respectively. Analyses of changes in serum calcium from baseline to the 1-year study end point were performed within and between each renal function group.
Among the veterans with an eCrCl <35 mL/min and eCrCl ≥35 mL/min, there were decreases in median serum calcium levels from baseline to study end point from 9.8 mg/dL (interquartile range [IQR], 9.4-10.2 mg/dL) to 9.3 mg/dL (IQR, 9.0-10.0 mg/dL; P = 0.028) and 9.6 mg/dL (IQR, 9.3-9.9 mg/dL) to 9.4 mg/dL (IQR, 9.1-9.8 mg/dL; P < 0.001), respectively. However, there was no difference in Δcalcium: -0.2 mg/dL (IQR, 0-0.6 mg/dL) and 0.2 mg/dL (IQR, -0.2 to 0.5 mg/dL; P = 0.547), respectively.
This exploratory assessment may suggest that, in elderly veterans, the initiation of oral bisphosphonate therapy contributed to a statistically significant decrease in serum calcium levels regardless of baseline renal function; however, the clinical impact of this change does not appear to be significant. Future studies should assess serum calcium in a larger population of patients to confirm the safety of oral bisphosphonates in poor kidney function.
由于肾衰竭患者经验不足导致存在禁忌证，关于肾功能不佳患者使用双膦酸盐的可用数据有限，在其他情况合适时，这一禁忌证导致高达25%的不处方情况。
如药品说明书所述（估计肌酐清除率[eCrCl]<35ml/min），确定肾功能下降患者使用双膦酸盐是否会像先前研究所暗示的那样导致更高的低钙血症发生率。
这是一项对德克萨斯州达拉斯退伍军人事务部北德克萨斯医疗系统65岁及以上老年退伍军人的回顾性队列研究。我们确定了2003年8月1日至2010年7月12日期间开始口服双膦酸盐治疗的3089名患者。在符合纳入标准的252名患者中，分别有25名和227名患者的eCrCl<35ml/min和eCrCl≥35ml/min。在每个肾功能组内及组间对从基线到1年研究终点的血清钙变化进行了分析。
在eCrCl<35ml/min和eCrCl≥35ml/min的退伍军人中，从基线到研究终点，血清钙中位数水平分别从9.8mg/dL（四分位间距[IQR]，9.4 - 10.2mg/dL）降至9.3mg/dL（IQR，9.0 - 10.0mg/dL；P = 0.028）和从9.6mg/dL（IQR，9.3 - 9.9mg/dL）降至9.4mg/dL（IQR，9.1 - 9.8mg/dL；P<0.001）。然而，钙变化量（Δ钙）无差异，分别为-0.2mg/dL（IQR，0 - 0.6mg/dL）和0.2mg/dL（IQR，-0.2至0.5mg/dL；P = 0.547）。
这项探索性评估可能表明，在老年退伍军人中，无论基线肾功能如何，开始口服双膦酸盐治疗都会导致血清钙水平出现统计学上的显著下降；然而，这一变化的临床影响似乎并不显著。未来的研究应在更多患者中评估血清钙，以确认口服双膦酸盐在肾功能不佳患者中的安全性。
