Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Center of Bone Diseases, Rheumatology Unit, Bone and Joint Department, Lausanne University Hospital and University of Lausanne, Rue Pierre-Decker 4, CH-1011, Lausanne, Switzerland.
Osteoporos Int. 2020 Dec;31(12):2485-2491. doi: 10.1007/s00198-020-05676-7. Epub 2020 Oct 15.
Denosumab discontinuation is associated with a rapid increase in bone resorption and a decrease in bone mineral density. Spontaneous vertebral fractures may occur as a side effect of the rebound of bone resorption. Cases of rebound-linked hypercalcemia have also been described, moderate in women with osteoporosis and breast cancer and severe in children receiving oncological doses of denosumab. We report the case of an adult woman with primary hyperparathyroidism and moderate hypercalcemia, treated with denosumab for osteoporosis, who developed severe hypercalcemia and spontaneous vertebral fractures (SVFs) after denosumab discontinuation. An 86-year-old woman with densitometric osteoporosis was treated for 3 years with 60 mg of subcutaneous denosumab every 6 months. She was known to have primary hyperparathyroidism, with a serum albumin-corrected calcium of 2.82 mmol/l (NV 2.15-2.5) at the end of denosumab effect. Nine months after the last denosumab injection, she was hospitalized due to worsening overall health. Clinical evaluation revealed severe hypercalcemia (calcium 3.35 mmol/l). Very high values of bone turnover markers (BTMs) suggested a rebound effect due to denosumab discontinuation. An X-ray showed multiple new SVFs. After injection of denosumab 60 mg, serum calcium rapidly decreased and BTMs were dramatically reduced. A surgical approach by minimally invasive parathyroidectomy allowed for definite resolution of hyperparathyroidism and hypercalcemia. This case suggests that hypercalcemia can be a side consequence of denosumab discontinuation, which can become severe when other causes of hypercalcemia, such as primary hyperparathyroidism, are present.
地舒单抗停药后会迅速引起骨吸收增加和骨密度降低。骨吸收反弹可能会导致自发性椎体骨折。也有描述称地舒单抗停药后会出现反弹相关的高钙血症，骨质疏松症和乳腺癌女性中度，接受地舒单抗肿瘤剂量的儿童严重。我们报告了一例原发性甲状旁腺功能亢进症和中度高钙血症的成年女性病例，该患者因骨质疏松症接受地舒单抗治疗，停药后出现严重高钙血症和自发性椎体骨折（SVFs）。一名 86 岁女性，骨密度骨质疏松症，接受皮下注射地舒单抗 60mg，每 6 个月一次，治疗 3 年。该患者患有原发性甲状旁腺功能亢进症，在结束地舒单抗治疗时血清白蛋白校正钙为 2.82mmol/l（NV 2.15-2.5）。最后一次注射地舒单抗后 9 个月，因整体健康状况恶化住院。临床评估显示严重高钙血症（钙 3.35mmol/l）。骨转换标志物（BTMs）的非常高值提示由于地舒单抗停药而出现反弹效应。X 射线显示多发性新的 SVFs。注射 60mg 地舒单抗后，血清钙迅速降低，BTMs 显著减少。微创甲状旁腺切除术的手术方法使甲状旁腺功能亢进和高钙血症得到明确缓解。该病例表明，高钙血症可能是地舒单抗停药的副作用，当存在其他引起高钙血症的原因，如原发性甲状旁腺功能亢进症时，高钙血症可能会变得严重。
