Koldkjær Sølling A S, Harsløf T, Kaal A, Rejnmark L, Langdahl B
Department of Endocrinology and Internal Medicine, THG, Aarhus University Hospital, Tage-Hansens Gade 2, 8000, Aarhus C, Denmark.
Department of Nuclear Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Osteoporos Int. 2016 Jul;27(7):2383-2386. doi: 10.1007/s00198-016-3535-5. Epub 2016 Apr 20.
Denosumab is used for treatment of osteoporosis. We present a case report of hypoparathyroid hypercalcemia and increased bone turnover associated with discontinuation of treatment for 10 years with denosumab. There is a need for evidence-based guidelines on discontinuation of long-term denosumab treatment to avoid side effects and preserving anti-fracture efficacy.
Denosumab is commonly used as an anti-resorptive agent for the treatment of osteoporosis. After discontinuation of denosumab, however, bone resorption increases again, and the bone mass gained during therapy is rapidly declining. Thus, treatment with denosumab is considered to be reversible.
We present a case report of asymptomatic hypoparathyroid hypercalcemia in a patient who discontinued long-term treatment with denosumab.
A 67-year-old woman with osteoporosis was treated with denosumab 60 mg subcutaneously every 6 months from 2004 to 2014. She received the last injection in May 2014. Routine biochemistry in November 2014 showed increased s-ionized calcium (I-Ca) 1.64 mmol/L (1.18-1.32 mmol/L) and suppressed p-parathyroid hormone (PTH) 1.6 pmol/L (1.6-6.9 pmol/L). The patient was extensively examined, but no underlying disease was found. In January 2015, the patient began treatment with alendronat 70 mg weekly. In April 2015, serum levels of type 1 collagen C-terminal cross-linked telopeptide, procollagen type 1 N-terminal propeptide and bone-specific alkaline phosphatase were still markedly elevated. From then on, I-Ca and PTH normalized and the bone turnover markers (BTM) decreased.
In this case report, we describe increased BTMs and hypercalcemia associated with discontinuation of 10 years treatment with denosumab. The increase in BTMs is assumed to be temporary and normalization is expected. Since denosumab is commonly used, there is an urgent need for evidence-based guidelines on discontinuation of long-term treatment, avoiding side effects and preserving anti-fracture efficacy.
地诺单抗用于治疗骨质疏松症。我们报告一例与停用10年地诺单抗治疗相关的甲状旁腺功能减退性高钙血症及骨转换增加的病例。需要有基于证据的关于停用长期地诺单抗治疗的指南,以避免副作用并保留抗骨折疗效。
地诺单抗通常用作治疗骨质疏松症的抗吸收剂。然而,停用后,骨吸收再次增加,且治疗期间获得的骨量迅速下降。因此,地诺单抗治疗被认为是可逆的。
我们报告一例停用长期地诺单抗治疗的患者出现无症状性甲状旁腺功能减退性高钙血症的病例。
一名67岁骨质疏松症女性患者在2004年至2014年期间每6个月皮下注射60mg地诺单抗。她于2014年5月接受最后一次注射。2014年11月的常规生化检查显示血清离子钙(I-Ca)升高至1.64mmol/L(1.18 - 1.32mmol/L),甲状旁腺激素(PTH)降低至1.6pmol/L(1.6 - 6.9pmol/L)。对该患者进行了全面检查,但未发现潜在疾病。2015年1月,患者开始每周服用70mg阿仑膦酸钠治疗。2015年4月,1型胶原C端交联羧基末端肽、1型前胶原N端前肽和骨特异性碱性磷酸酶的血清水平仍显著升高。从那时起,I-Ca和PTH恢复正常,骨转换标志物(BTM)下降。
在本病例报告中,我们描述了与停用10年地诺单抗治疗相关的BTM升高和高钙血症。BTM的升高被认为是暂时的,有望恢复正常。由于地诺单抗被广泛使用,迫切需要基于证据的关于停用长期治疗、避免副作用并保留抗骨折疗效的指南。