Yasuda Yoshinori, Iwama Shintaro, Arima Hiroshi
Department of Endocrinology and Diabetes, Nagoya University Hospital, Nagoya 466-8560, Japan.
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Endocr J. 2019 Mar 28;66(3):271-275. doi: 10.1507/endocrj.EJ18-0545. Epub 2019 Feb 2.
Primary sclerosing cholangitis (PSC) has been known as a cause of secondary osteoporosis, which often requires medication. Herein, we give the first report of a case of a 38-year-old man with fatigue and paralysis in both upper limbs who had been treated with denosumab for secondary osteoporosis associated with PSC. Since bisphosphonate (alendronate) was ineffective in our patient, the treatment was changed from alendronate to denosumab. Despite replacements with calcium and active vitamin D (alfacalcidol; 1-hydroxycholecalciferol), he developed severe hypocalcemia (albumin-adjusted serum calcium: 5.2 mg/dL) 2 weeks after the second administration of denosumab, which required immediate correction. After that, the corrected serum calcium levels were controlled within the normal range with 0.75 μg of eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3) and increased doses of calcium (1,500 mg daily) and phosphate (900 mg daily) without denosumab. Even though denosumab treatment had been terminated, the T score of the lumbar spine improved from -4.4 to -2.6 by 1 year after the second administration, possibly due to the amelioration of osteomalacia through the treatment with eldecalcitol and the higher doses of calcium and phosphate. This report indicates that denosumab can cause severe hypocalcemia in patients with osteoporosis associated with chronic diseases of the hepatobiliary system including PSC, in turn suggesting that the possibility of vitamin D deficiency or osteomalacia should be considered before administering treatments and that serum calcium levels should be closely monitored to detect life-threatening hypocalcemia in patients who have high risk factors for hypocalcemia.
原发性硬化性胆管炎（PSC）一直被认为是继发性骨质疏松症的一个病因，继发性骨质疏松症通常需要药物治疗。在此，我们首次报告了一例38岁男性患者，该患者因与PSC相关的继发性骨质疏松症接受地诺单抗治疗，出现疲劳及双上肢麻痹。由于双膦酸盐（阿仑膦酸钠）对我们的患者无效，治疗从阿仑膦酸钠改为地诺单抗。尽管补充了钙和活性维生素D（阿法骨化醇；1-羟胆钙化醇），但在第二次注射地诺单抗后2周，他出现了严重低钙血症（白蛋白校正血清钙：5.2mg/dL），这需要立即纠正。此后，在未使用地诺单抗的情况下，通过服用0.75μg的依地骨化醇（1α,25-二羟基-2β-(3-羟丙氧基)维生素D3）以及增加钙（每日1500mg）和磷酸盐（每日900mg）的剂量，校正后的血清钙水平被控制在正常范围内。尽管地诺单抗治疗已经终止，但在第二次给药后1年，腰椎的T值从-4.4改善到了-2.6，这可能是由于依地骨化醇以及较高剂量的钙和磷酸盐治疗改善了骨软化症。本报告表明，地诺单抗可导致患有包括PSC在内的肝胆系统慢性疾病相关骨质疏松症的患者出现严重低钙血症，进而提示在进行治疗前应考虑维生素D缺乏或骨软化症的可能性，并且对于有高钙血症危险因素的患者，应密切监测血清钙水平以检测危及生命的低钙血症。
