Browsing by Subject "Denosumab"

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    Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw
    (Springer, 2017-01) Yoneda, Toshiyuki; Hagino, Hiroshi; Sugimoto, Toshitsugu; Ohta, Hiroaki; Takahashi, Shunji; Soen, Satoshi; Taguchi, Akira; Nagata, Toshihiko; Urade, Masahiro; Shibahara, Takahiko; Toyosawa, Satoru; Department of Medicine, School of Medicine
    Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.
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    Objective tumor response to denosumab in patients with giant cell tumor of bone: a multicenter phase II trial
    (Oxford University Press, 2015-10) Ueda, T.; Morioka, H.; Kakunaga, S.; Tsuchiya, H.; Matsumoto, Y.; Asami, Y.; Inoue, T.; Yoneda, T.; Department of Medicine, IU School of Medicine
    BACKGROUND: Giant cell tumor of bone (GCTB) is a rare primary bone tumor, characterized by osteoclast-like giant cells that express receptor activator of nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor, denosumab, was predicted to reduce osteolysis and control disease progression in patients with GCTB. PATIENTS AND METHODS: Seventeen patients with GCTB were enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor response was evaluated prospectively by an independent imaging facility on the basis of prespecified criteria. RESULTS: The proportion of patients with an objective tumor response was 88% based on best response using any tumor response criteria. The proportion of patients with an objective tumor response using individual response criteria was 35% based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based on inverse Choi criteria. The median time of study treatment was 13.1 months. CONCLUSION: The findings demonstrate that denosumab has robust clinical efficacy in the treatment of GCTB.
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    Prolonged Hypocalcemia After a Single Dose of Denosumab in Chronic Kidney Disease
    (Endocrine Society, 2021-05-03) Puar, Akshan; Saeed, Zeb Ijaz; Endocrinology, IU School of Medicine
    Introduction: Denosumab, a monoclonal antibody that inhibits RANK L (receptor activator nuclear factor-kappa beta ligand), is one of the few medications that can be used to treat osteoporosis in patients with chronic kidney disease (CKD). However, its use is associated with a much higher incidence of hypocalcemia in this patient population. What remains unclear is the duration of hypocalcemia after denosumab use. We describe a case of prolonged hypocalcemia of 9 months in a patient with CKD after a single dose of denosumab. Case: A 64-year-old Caucasian man with a history of bilateral lung transplant for interstitial pulmonary fibrosis and CKD Stage IV was referred to the Endocrinology clinic for evaluation of steroid-induced osteoporosis. Bone density scan was consistent with osteoporosis with the lowest T-score of -2.8 at the left femoral neck, which showed a 25.3% decline from a previous one two years prior. His labs upon initial visit: 25 hydroxy Vitamin D: 36.5 ng/mL (30–100), 1, 25 hydroxy vitamin D 32 pg/ml (19.9–79.3), corrected Serum Calcium 8.9 mg/dL (8.5–10.5), Serum Cr 4.38 mg/dL (0.6–1.4), PTH 157 pg/mL (10–65), Serum Alkaline Phosphatase 61 Units/L (25–125), Urine NTX 39 nM BCE/mM creatinine (21–83). After discussing risks and benefits, he was given a dose of subcutaneous denosumab 60 mg. He had been started on Calcium/Vitamin D (600 mg/400 IU BID) prior to receiving his dose. Keeping in mind the increased risk of hypocalcemia given his history of CKD, his corrected serum calcium was checked one week later, and it was 6.5 mg/dL. The patient was asymptomatic. However, given the severity of his hypocalcemia, he was started on calcitriol 0.25 mcg oral BID and calcium carbonate 1200 mg daily. He did show mild improvement in three days to a corrected calcium of 7.0 mg/dL. His calcitriol was briefly increased to 0.5 mcg BID and calcium carbonate was increased to 1800 mg daily. The regimen was weaned to calcitriol 0.25 mcg daily and previous calcium/Vitamin D dosing later that month. Thereafter, his labs were monitored regularly and there were several unsuccessful attempts made to decrease the calcitriol/calcium carbonate. Given persistent hypocalcemia, other bloodwork including a bone specific alkaline phosphatase and celiac screen were checked which were unremarkable. Finally, nine months after his denosumab dose, calcitriol was discontinued safely. Serum calcium levels have remained stable thereafter. Given prolonged hypocalcemia, it was decided not to administer another dose of denosumab. Conclusion: Patients with CKD who receive denosumab are not only at risk for developing severe, but also prolonged hypocalcemia. Therefore, it is imperative to monitor serum calcium levels, not only immediately after receiving a dose, but serially.
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    SAT-512 Severe Hypocalcemia Presenting as Status Epilepticus after Denosumab Use in Metastatic Prostate Cancer
    (Oxford University Press, 2019-04-15) Saeed, Zeb; Aziz, Ammara; Medicine, School of Medicine
    Introduction: Denosumab decreases the incidence of skeletal-related events in patients with metastatic bone disease and is used routinely as part of the therapeutic strategy for various cancers. However, it is associated with a high risk of hypocalcemia with incidence of high-grade hypocalcemia (defined as total calcium < 7mg/dl) as high as 5.1% in patients with castrate-resistant prostate cancer. We present a case of severe hypocalcemia presenting with status epilepticus 32 days after administration of denosumab. Case: A 83 year old African American man presented to the emergency room with status epilepticus. Initial labs revealed a critically low calcium (Ca) of <5mg/dl (8.5-10.1) with albumin 2.2 g/dl (3.4-5.0), ionized calcium 1.09 mg/dl (4.6-5.1) and creatinine (Cr) 3.68 mg/dl (0.67-1.17). QTC was prolonged at 544ms (<400ms). He was intubated for airway protection and a continuous infusion of intravenous calcium gluconate was initiated. Three months prior, he had been diagnosed with prostate cancer with diffuse osteoblastic metastases to his ribs, cervical, thoracic, lumbar and sacral vertebrae, right humerus and bilateral iliac bones. He received a first dose of conventional chemotherapy and 120mg denosumab subcutaneously 32 days prior to hospital admission. Lab investigations then were pertinent for Ca of 9 mg/dl, Cr 1.46 mg/dl, and alkaline phosphatase 362 Units/L (25-125). A 25-hydroxy vitamin D (25-D) was not checked. Further evaluation demonstrated intact parathyroid hormone 677.2 pg/ml (18.4-80.1), alkaline phosphatase 397 Units/L, phosphorus 3.6 mg/dl (2.5-4.9) and 25-D 18 ng/ml (30-100). He was also found to have metastatic obstruction of both ureters which had resulted in acute kidney injury. He was slowly weaned off the intravenous calcium and started on calcitriol 2mcg twice daily, 4 gram elemental calcium daily via feeding tube and cholecalciferol 6000 units daily. Calcium levels remained stable at 8.0-8.5mg/dl on this regimen. Given the extensive metastatic disease, the patient’s family elected to pursue hospice care, and he passed away 9 days later. Conclusion: Patients with osteoblastic metastases and renal impairment are at particularly increased risk of hypocalcemia after denosumab, which can be potentially life-threatening. Physicians caring for patients with metastatic prostate cancer should ensure that vitamin D levels are replete and calcium levels are normal prior to administration of denosumab, monitor calcium levels closely, and counsel them about the signs and symptoms of hypocalcemia to allow prompt diagnosis and treatment.