The Calcium Culprit: A Case of Denosumab-induced Hypocalcemia

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Abstract

Denosumab is a fully human monoclonal antibody which is used to treat osteoporosis and has been shown to cause hypocalcemia in patients with underlying prostatic and bone malignancies, renal impairment, postmenopausal state, and/or vitamin D deficiency. We present a case of a male patient, with a past medical history negative for the aforementioned conditions, who presented with right shoulder pain and was found to be severely hypocalcemic secondary to denosumab.

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High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

Koji Ishikawa, Takashi Nagai, Keizo Sakamoto … (2016)

Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P 76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium.

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Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures.

Kenneth Pittman, Yoland C. Antill, Amanda Goldrick … (2017)

Denosumab, a bone-modifying agent, reduces the risk of skeletal-related events in patients with bone metastases from solid tumors and is generally well tolerated. However, hypocalcemia, osteonecrosis of the jaw (ONJ) and atypical fracture are potential and important toxicities of denosumab therapy that require attention. In pivotal phase III trials in patients with bone metastases from solid tumors, the incidence of hypocalcemia was 9.6% in denosumab-treated patients, with most events being asymptomatic, grade 2 and resolving by week 4. Established hypocalcaemia requires additional short-term calcium and vitamin D supplementation and, if severe, administration of intravenous calcium. ONJ was reported in 1.8% of patients receiving denosumab over 3 years in these trials. Involvement of an experienced oro-maxillary surgeon is important if ONJ is suspected. Atypical fractures were rare in a large study of denosumab using the dose and scheduling approved for the treatment of osteoporosis. To prevent toxicities, patients should maintain calcium and vitamin D supplementation, good oral hygiene and regular dental reviews throughout treatment. This article presents case studies from our clinical practice and discusses the pathophysiology of these toxicities along with guidance on prevention, diagnosis and management.

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A RANKL Wrinkle: Denosumab-Induced Hypocalcemia.

Larissa K. Laskowski, David Goldfarb, Mary Howland … (2016)

The human monoclonal antibody denosumab inhibits osteoclast-mediated bone resorption by binding to receptor activator of nuclear factor κB ligand (RANKL), which is upregulated by tumor cells. Denosumab is indicated to prevent skeletal-related events (SREs) from osteoporosis and metastatic bone disease. We report a case of denosumab-induced hypocalcemia to highlight potential toxicity and treatment considerations. A 66-year-old man with prostate cancer, small cell lung cancer, and bone metastases presented with fatigue, weakness, and muscle spasm. Sixteen days prior, he received cycle 6 of cisplatin and etoposide, leuprolide, and denosumab (120 mg subcutaneously). His examination demonstrated a slight resting tremor, normal strength, and negative Chvostek sign. Laboratory analysis revealed hemoglobin, 8.0 g/dL; total calcium, 5.2 mg/dL (pre-denosumab, 8.9 mg/dL); and magnesium, 0.7 mg/dL. He initially received two units packed red blood cells, intravenous calcium and magnesium, and vitamin D. During his hospitalization, he required multiple doses of intravenous and oral calcium, magnesium, and vitamin D. Despite ongoing oral supplementation, his post-discharge serum calcium fluctuated significantly, requiring close monitoring and frequent dose adjustments. Denosumab's unique antiresorptive properties yield fewer SREs. The trade-off is increased hypocalcemia risk, which may be severe and require aggressive, prolonged supplementation and monitoring.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 28 May 2019

Publication date (Electronic, collection): May 2019

Volume: 11

Issue: 5

Electronic Location Identifier: e4768

Affiliations

[1 ] Emergency Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, USA

[2 ] Internal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, USA

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Ricci Kalayanamitra ricci.kalaya@ 123456gmail.com

Article

DOI: 10.7759/cureus.4768

PMC ID: 6663059

PubMed ID: 31363449

SO-VID: a3d47221-be20-433a-87f5-f3037f2a312f

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The Calcium Culprit: A Case of Denosumab-induced Hypocalcemia

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Abstract

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Most cited references 15

High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures.

A RANKL Wrinkle: Denosumab-Induced Hypocalcemia.

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