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      Immobilization-induced hypercalcemia in a patient with renal failure

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          Abstract

          Summary

          Immobilization-induced hypercalcemia is an uncommon cause of elevated calcium which is usually diagnosed following extensive systemic workup and exclusion of more common etiologies. Previously reported cases have largely described this phenomenon in adolescents and young adults a few weeks to months after the initial onset of immobilization. Metabolic workup tends to demonstrate hypercalcemia, hypercalciuria, and eventual osteoporosis. While the exact mechanism remains largely unclear, a dysregulation between bone resorption and formation is central to the pathogenesis of this disease. Decreased mechanical loading from prolonged bedrest tends to increase osteoclast induced bone resorption while promoting osteocytes to secrete proteins such as sclerostin to reduce osteoblast mediated bone formation. We describe the case of an 18-year-old male who was admitted following intraabdominal trauma. He underwent extensive abdominal surgery including nephrectomy resulting in initiation of dialysis. After 6 months of hospitalization, the patient gradually began developing uptrending calcium levels. Imaging and laboratory workup were unremarkable for any PTH-mediated process, malignancy, thyroid disorder, adrenal disorder, or infection. Workup did reveal significant elevated bone turnover markers which in combination with the clinical history led the physicians to arrive at the diagnosis of immobilization induced hypercalcemia. In order to prevent decreased rates of bone loss, the patient was administered denosumab for treatment. Hypocalcemia followed treatment expectedly and was repleted with supplementation via the patient’s total parenteral nutrition.

          Learning points
          • Immobilization-induced hypercalcemia should remain as a differential diagnosis of patients with prolonged hospitalizations with hypercalcemia.

          • Extensive workup of common etiologies of hypercalcemia should be considered prior to arriving at this diagnosis.

          • Denosumab, while off-label for this usage, offers an effective treatment option for immobilization-induced hypercalcemia though it carries a risk of hypocalcemia especially among patients with renal disease.

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          Most cited references12

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          A practical approach to hypercalcemia.

          Hypercalcemia is a disorder commonly encountered by primary care physicians. The diagnosis often is made incidentally in asymptomatic patients. Clinical manifestations affect the neuromuscular, gastrointestinal, renal, skeletal, and cardiovascular systems. The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy. Some other important causes of hypercalcemia are medications and familial hypocalciuric hypercalcemia. An initial diagnostic work-up should include measurement of intact parathyroid hormone, and any medications that are likely to be causative should be discontinued. Parathyroid hormone is suppressed in malignancy-associated hypercalcemia and elevated in primary hyperparathyroidism. It is essential to exclude other causes before considering parathyroid surgery, and patients should be referred for parathyroidectomy only if they meet certain criteria. Many patients with primary hyperparathyroidism have a benign course and do not need surgery. Hypercalcemic crisis is a life-threatening emergency. Aggressive intravenous rehydration is the mainstay of management in severe hypercalcemia, and antiresorptive agents, such as calcitonin and bisphosphonates, frequently can alleviate the clinical manifestations of hypercalcemic disorders.
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            A RANKL Wrinkle: Denosumab-Induced Hypocalcemia.

            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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              Incidence of hypocalcemia and hypercalcemia in hospitalized patients: Is it changing?

              Highlights • Disorders of calcium metabolism are frequently encountered in clinical practice. • Hypocalcemia accounted for 27.72% and hypercalcemia for 4.74% of inpatients. • Incidence of hypo- and hypercalcemia changed over time.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                01 September 2021
                2021
                : 2021
                : 21-0086
                Affiliations
                [1 ]Division of Internal Medicine, University of Arizona, College of Medicine – Phoenix , Phoenix, Arizona, USA
                [2 ]Banner University Medical Center – Phoenix , Phoenix, Arizona, USA
                [3 ]Division of Endocrinology , Diabetes and Metabolism, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
                [4 ]Carl T Hayden Phoenix VA Medical Center , Phoenix, Arizona, USA
                Author notes
                Correspondence should be addressed to A Gandhi Email gandhiad4@ 123456gmail.com
                Article
                EDM210086
                10.1530/EDM-21-0086
                8558878
                34612208
                f84d1a0c-d5f1-43b6-9e4b-ec962c5bf2d4
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 29 August 2021
                : 01 September 2021
                Categories
                Adult
                Male
                Black - other
                United States
                Parathyroid
                Bone
                New Disease or Syndrome: Presentations/Diagnosis/Management
                New Disease or Syndrome: Presentations/Diagnosis/Management

                adult,male,black - other,united states,parathyroid,bone,new disease or syndrome: presentations/diagnosis/management,october,2021

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