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：

---

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？

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，地诺单抗治疗的绝经后骨质疏松症妇女低钙血症发生率在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的低钙血症发生率。方法回顾性分析根据大型HMO的病历（2010-2018）进行。经过白蛋白调整的血清钙浓度低于8。5 mg / dL被定义为低钙血症。结果我们纳入了2005年的患者（93％的女性，平均年龄76±9岁）。149名患者在治疗期间发生低血钙症（7.4％；低于8 mg / dL的患者为1％）：0.5-1年后为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）。低血钙血症的发生率与eGFR的下降同时增加（eGFR范围之间的差异p = 0.032）。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（3。低于则为7％，高于则为17.1％-17.4）。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先前报道。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。结论地诺单抗引起的低血钙症的实际发生率高于先前报道。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。结论地诺单抗引起的低血钙症的实际发生率高于先前报道。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。