Abstract

Summary

Hypocalcemia was reported at low rates (0.05–1.7%) in denosumab-treated postmenopausal women with osteoporosis. This real-life study shows a 7.4% rate of denosumab-induced hypocalcemia in community-dwelling osteoporotic men and women. Pretreatment serum calcium and creatinine levels are major predictors for this complication. Serum-calcium monitoring may help to identify and prevent severe hypocalcemia.

Purpose

RCTs have reported a 0.05–1.7% rate of hypocalcemia in denosumab-treated postmenopausal women with osteoporosis, but long-term real-life data are lacking. We assessed the rate of hypocalcemia in osteoporotic community-dwelling patients treated with denosumab.

Methods

A retrospective analysis was conducted based on medical records (2010–2018) from a large HMO. An albumin-adjusted serum calcium concentration lower than 8.5 mg/dL was defined as hypocalcemia.

Results

We included 2005 patients (93% women, mean age 76 ± 9 years). Hypocalcemia developed during treatment in 149 patients (7.4%; 1% less than 8 mg/dL): in 66 after 0.5–1 years; 48 after 1–2 years; 35 after > 2 years. On comparison of the hypocalcemic and normocalcemic patients, the strongest predictors of hypocalcemia were pretreatment levels of albumin-adjusted serum calcium (9.1 ± 0.4 vs. 9.4 ± 0.5 mg/dL, respectively; p < 0.05) and creatinine (0.9 ± 0.5 vs. 0.8 ± 0.3 mg/dL, respectively; p < 0.05). The hypocalcemia rate increased in parallel to a decrease in eGFR (p = 0.032 for the difference between eGFR ranges). Baseline calcium level ≤ 9.31 mg/dL predicted hypocalcemia with a sensitivity of 77% and specificity of 56%. A model of (− 2)*calcium + creatinine predicted hypocalcemia (3.7% when lower and 17.1% when higher than − 17.4). Gender, age, 25-hydroxyvitamin-D, parathyroid hormone, alkaline phosphatase, and whether denosumab was given as first or advanced line of osteoporotic therapy had no predictive value.

Conclusion

Real-life rates of denosumab-induced hypocalcemia are higher than previously reported. Hypocalcemia might develop after each dose of denosumab in ongoing treatment. Adequate calcium and vitamin D supplementation are needed. Serum calcium monitoring is advised in high-risk patients for early detection of severe hypocalcemia.

中文翻译：

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地诺单抗引起的骨质疏松症患者的低钙血症：您知道谁会降低吗？

摘要

概要

据报道，地诺单抗治疗的绝经后骨质疏松症妇女低钙血症发生率低（0.05–1.7％）。这项现实生活研究显示，在社区居住的骨质疏松症患者中，地诺单抗引起的低血钙症发生率为7.4％。预处理血清钙和肌酐水平是该并发症的主要预测指标。血清钙监测可能有助于识别和预防严重的低钙血症。

目的

RCTs报告称，经地诺单抗治疗的绝经后骨质疏松症妇女低血钙发生率在0.05–1.7％，但缺乏长期的现实生活数据。我们评估了用地诺单抗治疗的骨质疏松社区居民患者的低血钙发生率。

方法

根据大型HMO的病历（2010-2018年）进行了回顾性分析。经过白蛋白调整的血清钙浓度低于8.5 mg / dL的定义为低钙血症。

结果

我们纳入了2005年的患者（93％的女性，平均年龄76±9岁）。149名患者在治疗过程中发生低血钙症（7.4％；低于8 mg / dL的患者为1％）：0.5–1年后的患者中为66。1-2年后48；> 2年后为35。在比较低血钙和正常血钙患者时，低血钙的最强预测指标是经白蛋白调整的血清钙（分别为9.1±0.4和9.4±0.5 mg / dL；p  <0.05）和肌酐（0.9±0.5对。分别为0.8±0.3 mg / dL；p  <0.05）。低钙血症发生率增加，而eGFR下降（p = 0.032（eGFR范围之间的差异）。基线钙水平≤9.31 mg / dL可预测低钙血症，敏感性为77％，特异性为56％。（−2）*钙+肌酐的模型预测低血钙（低时为3.7％，高于-17.4时为17.1％）。性别，年龄，25-羟基维生素D，甲状旁腺激素，碱性磷酸酶以及是否将denosumab作为骨质疏松治疗的第一线或晚期线均无预测价值。

结论

地诺单抗引起的低血钙症的实际发生率高于以前的报道。在每次剂量的地诺单抗持续治疗后可能会发生低钙血症。需要足够的钙和维生素D补充。建议在高危患者中进行血清钙监测，以及早发现严重的低钙血症。