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BMC Veterinary Research May 2024Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an...
BACKGROUND
Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog.
CASE PRESENTATION
An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure.
CONCLUSIONS
Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.
Topics: Animals; Dogs; Pamidronate; Hypocalcemia; Male; Hypercalcemia; Dog Diseases; Glucocorticoids; Bone Density Conservation Agents; Diphosphonates
PubMed: 38790012
DOI: 10.1186/s12917-024-04030-x -
Malaysian Orthopaedic Journal Mar 2024The objective of this case series is to investigate the efficacy and safety of intravenous infusion of Pamidronate, a second generation bisphosphonate, in the treatment...
INTRODUCTION
The objective of this case series is to investigate the efficacy and safety of intravenous infusion of Pamidronate, a second generation bisphosphonate, in the treatment of active Charcot arthropathy.
MATERIALS AND METHODS
All patients with active Charcot arthropathy treated at the medical centre from 1 January 2013 to 30 June 2020 were included in the study. Efficacy outcome was evaluated based on time to consolidate findings observed through radiographic examination, while safety outcome was evaluated based on the incidence of adverse event (AE) occurrence.
RESULTS
A total of 81 patients (37 male, 44 female) diagnosed with active Charcot arthropathy were included. 64.2% of patients were at stage 1 of Charcot arthropathy whereas 35.8% were at stage 2. The mean time to consolidate for stage 1 and stage 2 was 6.50 ± 4.21 months and 3.63 ± 2.92 months respectively (p-value = 0.139). No significant association was observed between gender, ethnicity and disease stage with the consolidation time (p-value >0.05). The rate of AE incidence was 2.5%, observed in 2 patients who developed a fever during the treatment. No other serious AE was observed in the study.
CONCLUSION
Intravenous Pamidronate infusion is a safe and effective treatment option for Charcot arthropathy.
PubMed: 38638656
DOI: 10.5704/MOJ.2403.009 -
Journal of Community Hospital Internal... 2023Patients with granulomatous disease often have widespread pulmonary and extrapulmonary disease. In the absence of this, a search of the pulmonary, renal, hepatic,...
Patients with granulomatous disease often have widespread pulmonary and extrapulmonary disease. In the absence of this, a search of the pulmonary, renal, hepatic, ocular, and bone marrow is warranted in the setting of hypercalcemia with unexplained elevated 1,25-dihydroxyvitamin D, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). We present a case of hypercalcemia and a decline in renal function in a patient with bone marrow sarcoidosis. A 45-year-old woman was admitted to the hospital after hypercalcemia, acute kidney injury, and pancytopenia were found on a routine outpatient lab. She was discharged after improvement with IV fluids. She had interval worsening of hypercalcemia and was readmitted within a week for pamidronate treatment. Imaging and labs were concerning for sarcoidosis, but bronchoscopy with biopsy was nondiagnostic. Eventual bone marrow biopsy confirmed evidence of granulomas. Her condition improved with prednisone over 3 months and ultimately, azathioprine. Non-parathyroid hormone-mediated hypercalcemia should be thoroughly worked up for a source to rule out malignancy and to diagnose treatable causes such as sarcoidosis. Sarcoidosis may not present in its traditional pulmonary pattern, necessitating further diagnostic measures such as a bone marrow biopsy.
PubMed: 38596540
DOI: 10.55729/2000-9666.1257 -
Burns : Journal of the International... Aug 2024To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength.
METHODS
A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn.
RESULTS
Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% ( ± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support.
CONCLUSIONS
Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers.
Topics: Humans; Burns; Body Composition; Child; Muscle Strength; Body Weight; Body Height; Exercise Therapy; Nutritional Support; Treatment Outcome
PubMed: 38580580
DOI: 10.1016/j.burns.2024.03.012 -
Clinical Pediatric Endocrinology : Case... 2024We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a...
We report the case of a patient with osteogenesis imperfecta (OI) who developed pulmonary hemorrhage 4 d after pamidronate disodium (PA) administration, despite a relatively stable respiratory status. Bisphosphonates are introduced to reduce osteoclast activity and are now widely used in patients with OI. Bisphosphonates are typically well-tolerated in children, and the standard of care involves cyclic intravenous administration of PA. However, in practice, there is limited experience with the use of PA for severe OI during the neonatal period, and its safety remains uncertain. This report aimed to describe the respiratory events potentially associated with PA in a neonatal patient with OI type 2, suggesting that serious life-threatening complications of pulmonary hemorrhage may occur after PA administration. Further studies are required to assess the relationship between pulmonary hemorrhage and PA administration, aiming to enhance prophylaxis measures.
PubMed: 38572388
DOI: 10.1297/cpe.2023-0061 -
FEBS Open Bio May 2024Drug repurposing is promising because approving a drug for a new indication requires fewer resources than approving a new drug. Signature reversion detects drug...
Drug repurposing is promising because approving a drug for a new indication requires fewer resources than approving a new drug. Signature reversion detects drug perturbations most inversely related to the disease-associated gene signature to identify drugs that may reverse that signature. We assessed the performance and biological relevance of three approaches for constructing disease-associated gene signatures (i.e., limma, DESeq2, and MultiPLIER) and prioritized the resulting drug repurposing candidates for four low-survival human cancers. Our results were enriched for candidates that had been used in clinical trials or performed well in the PRISM drug screen. Additionally, we found that pamidronate and nimodipine, drugs predicted to be efficacious against the brain tumor glioblastoma (GBM), inhibited the growth of a GBM cell line and cells isolated from a patient-derived xenograft (PDX). Our results demonstrate that by applying multiple disease-associated gene signature methods, we prioritized several drug repurposing candidates for low-survival cancers.
Topics: Drug Repositioning; Humans; Antineoplastic Agents; Animals; Cell Line, Tumor; Mice; Glioblastoma; Gene Expression Profiling; Xenograft Model Antitumor Assays; Gene Expression Regulation, Neoplastic; Brain Neoplasms; Neoplasms; Transcriptome
PubMed: 38531616
DOI: 10.1002/2211-5463.13796 -
CMAJ : Canadian Medical Association... Mar 2024
Topics: Humans; Scleritis; Pamidronate; Uveitis, Anterior; Acute Disease
PubMed: 38527748
DOI: 10.1503/cmaj.230859-f -
Annals of Pediatric Endocrinology &... Feb 2024Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream...
PURPOSE
Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children.
METHODS
We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events.
RESULTS
The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ.
CONCLUSION
Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.
PubMed: 38461805
DOI: 10.6065/apem.2346028.014 -
Bone May 2024Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is...
INTRODUCTION
Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is bisphosphonate therapy. Previous animal studies have shown that bisphosphonates delay tooth eruption. The aim of this study is to determine whether patients with OI treated with pamidronate and/or zoledronic acid have a delayed eruption age compared to a control group of healthy children.
METHODS
An ambispective longitudinal cohort study evaluating the age of eruption of the first stage mixed dentition in a group of children with OI (n = 37) all treated with intravenous bisphosphonates compared with a group of healthy children (n = 89). Within the study group, the correlation (Pearson correlation test) between the type of medication administered (pamidronate and/or zoledronic acid) and the chronology of tooth eruption is established, as well as the relationship between the amount of cumulative dose received and tooth eruption.
RESULTS
The age of eruption of the study group was significantly delayed compared to the age of eruption of the control group for molars and lateral incisors (p < 0.05). Patients who received higher cumulative doses had a delayed eruption age compared to those with lower cumulative doses (p < 0.05). There is a high positive correlation between age of delayed tooth eruption and Zoledronic acid administration.
CONCLUSION
Patients with OI have a delayed eruption of the 1st stage mixed dentition compared to a control group of healthy children. This delayed eruption is directly related to the cumulative dose of bisphosphonates and the administration of zoledronic ac.
Topics: Child; Animals; Humans; Pamidronate; Zoledronic Acid; Osteogenesis Imperfecta; Tooth Eruption; Bone Density Conservation Agents; Longitudinal Studies; Diphosphonates; Bone Density
PubMed: 38458305
DOI: 10.1016/j.bone.2024.117069 -
Toxicology in Vitro : An International... May 2024Podocytes play a critical role in the formation and maintenance of the glomerular filtration barrier and injury to these cells can lead to a breakdown of the glomerular...
Podocytes play a critical role in the formation and maintenance of the glomerular filtration barrier and injury to these cells can lead to a breakdown of the glomerular barrier causing permanent damage leading to progressive chronic kidney disease. Matured podocytes have little proliferative potential, which makes them critical cells from a health perspective, but also challenging cells to maintain in vitro. Differentiating podocyte-like cells from induced pluripotent stem cells (iPSC) provides a novel and continuous source of cells. Here, we investigated the effect of a 24-h exposure to eight compounds, including the known glomerular toxins doxorubicin and pamidronate, on transcriptomic alterations in iPSC derived podocytes. Doxorubicin (50 nM), pamidronate (50 μM), sodium arsenite (10 μM), and cyclosporine A (15 μM) had a strong impact on the transcriptome, gentamicin (450 μg/ml), lead chloride (15 μM) and valproic acid (500 μM) had a mild impact and busulfan (50 μM) exhibited no impact. Gene alterations and pathways analysis provided mechanistic insight for example, doxorubicin exposure affected the p53 pathway and dedifferentiation, pamidronate activated several pathways including HIF1alpha and sodium arsenite up-regulated oxidative stress and metal responses. The results demonstrate the applicability of iPSC derived podocytes for toxicological and mechanistic investigations.
Topics: Humans; Podocytes; Induced Pluripotent Stem Cells; Transcriptome; Xenobiotics; Pamidronate; Doxorubicin; Gene Expression Profiling; Sodium Compounds; Arsenites
PubMed: 38447685
DOI: 10.1016/j.tiv.2024.105804