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Molecules (Basel, Switzerland) Nov 2022[F]sodium fluoride ([F]NaF) is recognised to be superior to [mTc]-methyl diphosphate ([Tc]Tc-MDP) and ([F]FDG) in bone imaging. However, there is concern that [F]NaF...
[F]sodium fluoride ([F]NaF) is recognised to be superior to [mTc]-methyl diphosphate ([Tc]Tc-MDP) and ([F]FDG) in bone imaging. However, there is concern that [F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (/), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [F]AlF-NOTA-pamidronic acid was as sensitive as [F]sodium fluoride ([F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [F]NaF was higher in both cell lines, but [F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.
Topics: Humans; Fluorine Radioisotopes; Pamidronate; Sodium Fluoride; Chromatography, Liquid; Heterocyclic Compounds; Oligopeptides; Tandem Mass Spectrometry; Positron-Emission Tomography
PubMed: 36432069
DOI: 10.3390/molecules27227969 -
Medicine Nov 2022Most patients with parathyroid adenomas are asymptomatic and rarely present with chronic pancreatitis (CP). Several studies have reported a positive association between... (Review)
Review
BACKGROUND
Most patients with parathyroid adenomas are asymptomatic and rarely present with chronic pancreatitis (CP). Several studies have reported a positive association between primary hyperparathyroidism (PHPT) and pancreatitis. Parathyroidectomy is the definitive treatment for PHPT. IV bisphosphonates can be considered the drug of choice for bridge to surgery.
METHODS
We reported a 57-year-old female patient was admitted to the emergency room with left upper quadrant abdominal pain and a diagnosis of recurrent pancreatitis. Magnetic Resonance Cholangiopancreatography confirmed the diagnosis of CP. The patient had no common etiology of pancreatitis. Persistent hypercalcemia was noted despite administering intravenous fluids, and Calcitonin. Intravenous Pamidronate, a Bisphosphonate derivative, was also administered. Although calcium levels initially decreased, they were later found to rebound to previous levels.
RESULTS
A diagnosis of parathyroid adenoma and PHPT was made based on the elevated parathyroid hormone levels and cervical ultrasonography indicated right inferior parathyroid adenoma. Technetium-99m methoxy-isobutyl-isonitrile scintigraphy revealed a focal hot spot of tracer accumulation at the right lower thyroid bed. The patient underwent right lower parathyroidectomy smoothly and successfully. After right lower parathyroidectomy, she had normal serum calcium levels (9.2 mg/dL) and parathyroid hormone (16.1 pg/mL). There was no recurrent abdominal pain after the operation.
CONCLUSION
CP is a rare manifestation of parathyroid adenoma. When patients with a history of recurrent pancreatitis, without common causes of pancreatitis, present persistent elevated serum calcium levels, PHPT could be suspected.
Topics: Humans; Female; Middle Aged; Parathyroid Neoplasms; Calcium; Pancreatitis, Chronic; Hypercalcemia; Parathyroid Hormone; Abdominal Pain
PubMed: 36401406
DOI: 10.1097/MD.0000000000031750 -
Indian Dermatology Online Journal 2022Idiopathic calcinosis is a disorder characterized by diffuse calcium deposits at various sites of the body. Etiopathogenic associations are described with inherited...
Idiopathic calcinosis is a disorder characterized by diffuse calcium deposits at various sites of the body. Etiopathogenic associations are described with inherited disorders, connective tissue disorders, infections, tumors, trauma, and endocrine disturbances. No diagnostic tests or standard therapeutic guidelines are established for this entity. There is paucity of literature on idiopathic calcinosis. We describe a girl child with extensive calcinosis in the skin and around muscle bundles without any clinical and laboratory evidence for etiological associations. Aggressive treatment modalities resulted a notable improvement in lesions in index child. Growing evidence will help to establish the ground for understanding and developing standard therapy.
PubMed: 36386760
DOI: 10.4103/idoj.idoj_184_22 -
Frontiers in Pharmacology 2022This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application....
This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application. According to the FDA's Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose "Osteonecrosis of the jaw (10064658)" and "Exposed bone in jaw (10071014)" as preferred terms, "antiresorptive drugs" as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study. The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for "metabolic bone disorders" were the lowest for each drug, while HLT ROR values were high for "tumor-related indications," including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively. When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors.
PubMed: 36339548
DOI: 10.3389/fphar.2022.1017391 -
Endocrinology and Metabolism (Seoul,... Oct 2022Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries,...
Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.
Topics: Humans; Osteitis Deformans; Diphosphonates; Pamidronate; Bone and Bones; Bone Resorption
PubMed: 36327984
DOI: 10.3803/EnM.2022.1575 -
Successful Management of Severe Hypercalcemia with Zoledronic Acid: A Report of Two Pediatric Cases.Journal of Clinical Research in... May 2024Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with...
Severe hypercalcemia associated with vitamin D intoxication or malignancy in children is a rare and life-threatening condition. There is little published experience with Zoledronic acid (ZA) in the treatment of pediatric severe hypercalcemia. Here, we present two pediatric cases of severe hypercalcemia, one due to vitamin D intoxication and the second to malignancy, in which ZA was used as the first-line bisphosphonate in the treatment. While both cases responded well to a single dose of ZA, the second case experienced hypocalcemia requiring calcium treatment after ZA infusion. Our report shows that ZA may be an effective option in the treatment of severe pediatric hypercalcemia, although patients should be followed closely after infusion due to the risk of hypocalcemia. We provide additional published evidence for the effectiveness of ZA in correcting severe pediatric hypercalcemia and hope this will encourage future studies with larger numbers of patients.
Topics: Humans; Zoledronic Acid; Hypercalcemia; Bone Density Conservation Agents; Female; Male; Child; Child, Preschool; Treatment Outcome; Diphosphonates; Hypocalcemia; Imidazoles
PubMed: 36264042
DOI: 10.4274/jcrpe.galenos.2022.2022-9-3 -
Pediatric Rheumatology Online Journal Oct 2022The objectives were to assess changes in radiological disease activity in children with chronic non-bacterial osteomyelitis (CNO) receiving pamidronate therapy and to...
OBJECTIVES
The objectives were to assess changes in radiological disease activity in children with chronic non-bacterial osteomyelitis (CNO) receiving pamidronate therapy and to test a modified radiological index for non-bacterial osteitis (mRINBO) in CNO. mRINBO was used for standardized reporting and quantification of whole-body MRI (WBMRI) findings resulting in an individual summary patient score.
METHODS
WBMRI was retrospectively assessed in 18 children with CNO at baseline and after receiving pamidronate therapy for one year. Parameters of interest were: number and anatomic site of radiologically active bone lesions (RAL), size of RAL, extramedullary affection, spinal involvement and changes in mRINBO, which includes both the number and maximal size of RAL (RALmax) in addition to extramedullary and chronic changes.
RESULTS
At the time of diagnosis, the mean age of the children was 9.8 (sd, 8.7-10.9) years and 11/18 were females. The number of RALs per patient decreased from median [interquartile range] 4.5 [3-8] to 3 [2-5] RALs per patient (p = 0.02) and extramedullary inflammatory changes regressed. Sixty-one percent of all RALs occurring at baseline resolved and three children became without active inflammatory lesions by WBMRI. The median size of RALs did not change when taking new lesions occurring in 7/18 children into account, but RALmax decreased significantly from 39 [29-45] mm at baseline to 28 [20-40] mm (p < 0.01) at year-one with a concomitant decrease of mRINBO from a median of 5 [4-7] to 4 [3-5] (p = 0.05).
CONCLUSIONS
Pamidronate therapy resulted in a decrease of mRINBO from baseline to year one. mRINBO may be a potential scoring method to quantify changes in radiological disease activity in children with CNO. However, further studies are needed to test feasibility and validity of mRINBO.
Topics: Child; Chronic Disease; Female; Humans; Magnetic Resonance Imaging; Male; Osteitis; Osteomyelitis; Pamidronate; Retrospective Studies; Treatment Outcome
PubMed: 36183086
DOI: 10.1186/s12969-022-00746-y -
Journal of Clinical Orthopaedics and... Nov 2022Bisphosphonates and monoclonal antibodies are drugs primarily developed to inhibit osteoclast-mediated bone resorption and are used to treat an array of skeletal...
BACKGROUND
Bisphosphonates and monoclonal antibodies are drugs primarily developed to inhibit osteoclast-mediated bone resorption and are used to treat an array of skeletal pathologies. Their use is aimed at increasing bone health and therefore reducing fracture risks. The aim of this study was to evaluate the effectiveness of bone protection therapy on improving bone mineral density (BMD) in patients following a fracture.
METHODS
Inclusion criteria consisted of patients who sustained a skeletal fracture and were subsequently commenced on bone protection therapy. Dual-energy X-ray Absorptiometry (DEXA) scans were performed at baseline and following a consented period of drug therapy. Bone health data included T-Scores, Z-Scores, FRAX Major, FRAX Hip and BMD. The clinical effectiveness of four bisphosphonates (alendronate, risedronate, pamidronate and zoledronate) and one monoclonal antibody (denosumab) were evaluated.
RESULTS
A total of 100 patients were included in the study. Overall, bone protection therapy significantly improved Z-score Hip, Z-score Spine, T-score Spine and BMD Spine (p < 0.05). There was a marked difference between drug therapies. Denosumab and zoledronate were associated with the greatest treatment effect size. Alendronate only improved Z-score Spine and Z-score Hip (p < 0.05). Pamidronate and risedronate did not demonstrate any statistically significant improvement across any DEXA parameter.
CONCLUSION
Overall, bisphosphonates/monoclonal antibodies confer beneficial effects on bone health as measured by DEXA scans in patients following skeletal fractures. However, the magnitude of improvement varies among the commonly used drugs. Alendronate, zoledronate and denosumab were associated with greatest therapeutic benefit. Bone protection therapy did not improve fracture risk of patients (FRAX scores).
PubMed: 36161063
DOI: 10.1016/j.jcot.2022.102022 -
Oxidative Medicine and Cellular... 2022Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown.
AIM
The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs.
RESULTS
Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31; - score = 0.93), prednisone (SMD -2.38, 95% CI -3.09 to -1.67; - score = 0.92), levetiracetam (SMD -2.11, 95% CI -2.97 to -1.26; - score = 0.87), lamotrigine (SMD -1.39, 95% CI -2.21 to -0.58; - score = 0.73), etanercept (SMD -0.92, 95% CI -1.8 to -0.03; - score = 0.59), and pregabalin (SMD -0.46, 95% CI -0.71 to -0.22; - score = 0.41) had significantly better treatment effect. Pamidronate, prednisone, and levetiracetam ranked as the first three most effective treatments. In subgroup analyses, prednisone, levetiracetam, lamotrigine, and pregabalin were more effective than placebo as oral pharmacotherapies, while etanercept was more effective than placebo as injectable pharmacotherapy.
CONCLUSIONS
Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.
Topics: Anticonvulsants; Etanercept; Humans; Lamotrigine; Levetiracetam; Network Meta-Analysis; Pain; Pamidronate; Prednisone; Pregabalin
PubMed: 36035203
DOI: 10.1155/2022/3511385 -
Frontiers in Veterinary Science 2022This study aimed to describe a case of glomerulosclerosis resulting in nephrotic syndrome following the administration of pamidronate disodium to treat clinical...
OBJECTIVE
This study aimed to describe a case of glomerulosclerosis resulting in nephrotic syndrome following the administration of pamidronate disodium to treat clinical calcitriol toxicity in a dog.
CASE SUMMARY
A 12-week-old intact male Labrador Retriever weighing 11.8 kg presented with lethargy and vomiting for 20 h after ingesting a 100 g tube of topical antipsoriatic cream (3 mcg/g of calcitriol; Vectical Ointment™, Galderma, Lausanne, Switzerland). Severe hypercalcemia was present on the day of the presentation. Hypercalcemia treatments such as saline diuresis, furosemide (Salix, furosemide, Merck Animal Health, Kenilworth, NJ), and dexamethasone sodium phosphate (Dexamethasone SP, Mylan, Canonsburg, PA) were initiated. The dog was also administered a single dose of pamidronate disodium (Pamidronate disodium, Mylan, Canonsburg, PA) on the day of presentation. Initially, the patient's clinical signs improved, and the hypercalcemia resolved. Exactly 130 h post-pamidronate disodium (Dexamethasone SP, Mylan, Canonsburg, PA) administration, the patient developed biochemical abnormalities and severe edema, consistent with nephrotic syndrome, and was euthanized. Necropsy results revealed evidence of focal segmental glomerulosclerosis (FSGS).
UNIQUE INFORMATION
Pamidronate disodium, commonly used for the treatment of hypercalcemia, may have resulted in glomerulosclerosis and nephrotic syndrome in a dog with calcitriol toxicity. This complication should be taken into consideration when monitoring patients treated with pamidronate disodium for hypercalcemia.
PubMed: 36032307
DOI: 10.3389/fvets.2022.956153