Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment
Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment
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DOI：
10.1007/s00198-006-0189-8
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Krege, J. H.
中科院分区：
文献类型：
--
作者：
Miller, P. D.;Schwartz, E. N.;Krege, J. H.
骨质疏松症和肾功能损害的患病率随着年龄的增长而增加。方法利用骨折预防试验的数据，探讨特立帕肽[rhPTH(1-34)]治疗绝经后骨质疏松合并肾功能损害妇女的安全性和有效性。骨密度（BMD）和1型前胶原氨基末端延伸肽（PINP）分析要求患者血清肌酐浓度= 80 ml/min，肾功能轻度受损（GFR 50-79 ml/min）或中度受损（GFR 30-49 ml/min），骨折分析要求肾功能正常（GFR >= 80 ml/min）或肾功能受损（GFR < 80 ml/min）。结果与结论与肾功能正常患者相比，肾功能损害患者年龄大、身高矮、体重轻、绝经后时间长、腰椎和股骨颈基线骨密度低。与安慰剂相比，特立帕肽显著增加了各肾功能亚组的PINP、腰椎和股骨颈骨密度，没有证据表明肾功能不全改变了这些增加（各亚组治疗相互作用p < 0.05）。同样，特立帕肽介导的椎体和非椎体骨折风险降低相似，在肾功能正常或受损的患者之间没有显著差异（按亚组相互作用治疗p > 0.05）。在正常、轻度肾功能受损和中度肾功能受损亚组中，治疗后出现的不良事件和肾脏相关不良事件的发生率是一致的。特立帕肽诱导的平均GFR变化不受基线肾功能的影响（正常、轻度损害或中度损害亚组的治疗-肾功能相互作用p < 0.05）。与安慰剂相比，接受特立帕肽20或40 mcg治疗的所有肾功能类别患者在给药后4-6小时血清钙bb0的发生率增加10.6 mg/dl（正常上限）；然而，在任何肾功能类别中，特立帕肽20微克/天与给药后4-6小时血清钙bb0 11毫克/分升的发生率无显著增加相关。特立帕肽治疗与尿酸升高的发生率增加相关，在肾功能中度受损的患者和接受特立帕肽40微克/天的患者中，尿酸升高的发生率最高。即便如此，不良事件数据并未显示在特立帕肽治疗的正常、轻度或中度肾功能损害患者中痛风、关节痛或肾结石事件的发生率增加。
Introduction The prevalence of both osteoporosis and renal impairment increases with age.Methods Using data from the Fracture Prevention Trial, the safety and efficacy of teriparatide [rhPTH(1-34)] in postmenopausal women with osteoporosis and renal impairment were explored. Patients were required to have serum creatinine concentrations = 80 ml/min), mildly impaired (GFR 50-79 ml/min), or moderately impaired (GFR 30-49 ml/min) renal function for bone mineral density (BMD) and amino-terminal extension peptide of procollagen type 1 (PINP) analyses, and normal (GFR >= 80 ml/min) or impaired (GFR < 80 ml/min) renal function for fracture analyses.Results and conclusion Compared with patients with normal renal function, patients with renal impairment were older, shorter, weighed less, had been postmenopausal longer, and had lower baseline lumbar spine and femoral neck BMD. Compared with placebo, teriparatide significantly increased PINP and lumbar spine and femoral neck BMD within each renal function subgroup, and there was no evidence that these increases were altered by renal insufficiency (each treatment-by-subgroup interaction p > 0.05). Similarly, teriparatide-mediated vertebral and nonvertebral fracture risk reductions were similar and did not differ significantly between patients with normal or impaired renal function (treatment-by-subgroup interactions p > 0.05). The incidences of treatment-emergent and renal-related adverse events were consistent across treatment assignment in the normal, mildly impaired, and moderately impaired renal function subgroups. Teriparatide induced changes in mean GFR were unaffected by baseline renal function (treatment-by-renal function interaction p > 0.05 for normal, mildly impaired, or moderately impaired subgroups). Patients in all renal function categories treated with teriparatide 20 or 40 mcg had an increased incidence of 4-6-h postdose serum calcium > 10.6 mg/dl (the upper limit of normal) versus placebo; however, teriparatide 20 mcg/day was not associated with significantly increased incidence of 4-6-h postdose serum calcium > 11 mg/dl in any renal function category.Teriparatide therapy was associated with increased incidence of elevated uric acid, with the incidences being highest in patients with moderately impaired renal function and in those receiving teriparatide 40 mcg/day. Even so, adverse event data did not suggest an increased incidence of gout or arthralgia or of nephrolithiasis events in teriparatide-treated patients with normal, mild, or moderate renal impairment.