-
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 -
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 -
Molecules (Basel, Switzerland) Jun 2020Early diagnosis of bone metastases is crucial to prevent skeletal-related events, and for that, the non-invasive techniques to diagnose bone metastases that make use of...
Early diagnosis of bone metastases is crucial to prevent skeletal-related events, and for that, the non-invasive techniques to diagnose bone metastases that make use of image-guided radiopharmaceuticals are being employed as an alternative to traditional biopsies. Hence, in the present work, we tested the efficacy of a gallium-68 (Ga)-based compound as a radiopharmaceutical agent towards the bone imaging in positron emitting tomography (PET). For that, we prepared, thoroughly characterized, and radiolabeled [Ga]Ga-NODAGA-pamidronic acid radiopharmaceutical, a Ga precursor for PET bone cancer imaging applications. The preparation of NODAGA-pamidronic acid was performed via the -Hydroxysuccinimide (NHS) ester strategy and was characterized using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (MS). The unreacted NODAGA chelator was separated using the ion-suppression reverse phase-high performance liquid chromatography (RP-HPLC) method, and the freeze-dried NODAGA-pamidronic acid was radiolabeled with Ga. The radiolabeling condition was found to be most optimum at a pH ranging from 4 to 4.5 and a temperature of above 60 °C. From previous work, we found that the pamidronic acid itself has a good bone binding affinity. Moreover, from the analysis of the results, the ionic structure of radiolabeled [Ga]Ga-NODAGA-pamidronic acid has the ability to improve the blood clearance and may exert good renal excretion, enhance the bone-to-background ratio, and consequently the final image quality. This was reflected by both the in vitro bone binding assay and in vivo animal biodistribution presented in this research.
Topics: Acetates; Animals; Bone and Bones; Chromatography, High Pressure Liquid; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Male; Mass Spectrometry; Pamidronate; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 32526838
DOI: 10.3390/molecules25112668 -
CMAJ : Canadian Medical Association... Mar 2024
Topics: Humans; Scleritis; Pamidronate; Uveitis, Anterior; Acute Disease
PubMed: 38527748
DOI: 10.1503/cmaj.230859-f -
International Journal of Cancer Aug 2015Bisphosphonates are osteoclast inhibitors, currently being used in oncology to prevent or delay bone morbidity in cancer. Oral and intravenous formulations of... (Review)
Review
Bisphosphonates are osteoclast inhibitors, currently being used in oncology to prevent or delay bone morbidity in cancer. Oral and intravenous formulations of bisphosphonates have been found to be efficacious in preventing skeletal-related events such as bone pain, pathologic fractures, spinal cord compression and hypercalcemia of malignancy, in patients with bone metastatic breast cancer. Bisphosphonates are also used to prevent bone loss associated with anti-estrogen therapy using aromatase inhibitors. In addition to its role in preventing bone resorption, several pre-clinical studies have noted an anti-tumor role as well. Recent research effort has particularly focused on investigating an adjuvant role for bisphosphonates in early breast cancer. Recently, few randomized trials have found a beneficial effect for adjuvant use of the aminobisphosphonate, zoledronate, in older patients who are post-menopausal. This review article will summarize the various clinical studies investigating the role of bisphosphonates in breast cancer.
Topics: Aromatase Inhibitors; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Diphosphonates; Female; Humans
PubMed: 24824552
DOI: 10.1002/ijc.28965 -
Frontiers in Oral Health 2021Medication-related osteonecrosis of the jaw (MRONJ) is a growing problem without an effective treatment, presenting as necrotic bone sections exposed via lesions in the... (Review)
Review
Medication-related osteonecrosis of the jaw (MRONJ) is a growing problem without an effective treatment, presenting as necrotic bone sections exposed via lesions in the overlying soft tissue. There is currently a lack of clarity on how the factors involved in MRONJ development and progression contribute to disease prognosis and outcomes. Bisphosphonates (BPs), the most common cause of MRONJ, affect bone remodeling, angiogenesis, infection, inflammation and soft tissue toxicity, all of which contribute to MRONJ development. This article reviews the cellular mechanisms through which BPs contribute to MRONJ pathology, with a focus on the effects on cells of the oral mucosa. BPs have been shown to reduce cell viability, reduce proliferation, and increase apoptosis in oral keratinocytes and fibroblasts. BPs have also been demonstrated to reduce epithelial thickness and prevent epithelial formation in three-dimensional tissue engineered models of the oral mucosa. This combination of factors demonstrates how BPs lead to the reduced wound healing seen in MRONJ and begins to uncover the mechanisms through which these effects occur. The evidence presented here supports identification of targets which can be used to develop novel treatment strategies to promote soft tissue wound healing and restore mucosal coverage of exposed bone in MRONJ.
PubMed: 35224540
DOI: 10.3389/froh.2021.822411 -
Kidney International Dec 2008Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral... (Review)
Review
Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral bisphosphonates are used mainly to treat PMO and are not associated with significant nephrotoxicity. In contrast, nephrotoxicity is a significant potential limiting factor to the use of intravenous (IV) bisphosphonates, and the nephrotoxicity is both dose-dependent and infusion time-dependent. The two main IV bisphosphonates available to treat hypercalcemia of malignancy and osteolytic bone disease in the United States are zoledronate and pamidronate. Patterns of nephrotoxicity described with these agents include toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis, respectively. With both of these agents, severe nephrotoxicity can be largely avoided by stringent adherence to guidelines for monitoring serum creatinine prior to each treatment, temporarily withholding therapy in the setting of renal insufficiency, and adjusting doses in patients with pre-existing chronic kidney disease. In patients with PMO, zoledronate and pamidronate are associated with significantly less nephrotoxicity, which undoubtedly relates to the lower doses and longer dosing intervals employed for this indication. Ibandronate is approved in the US for treatment of PMO and in Europe for treatment of PMO and malignancy-associated bone disease. Available data suggest that ibandronate has a safe renal profile without evidence of nephrotoxicity, even in patients with abnormal baseline kidney function.
Topics: Diphosphonates; Glomerulosclerosis, Focal Segmental; Humans; Imidazoles; Kidney Cortex Necrosis; Kidney Diseases; Pamidronate; Practice Guidelines as Topic; Zoledronic Acid
PubMed: 18685574
DOI: 10.1038/ki.2008.356 -
Cancer Feb 2003Metastasis to the skeleton occurs in approximately 75% of patients with advanced breast cancer. It is the cause of much morbidity and decreased quality of life in these... (Clinical Trial)
Clinical Trial Review
BACKGROUND
Metastasis to the skeleton occurs in approximately 75% of patients with advanced breast cancer. It is the cause of much morbidity and decreased quality of life in these patients.
METHODS
Zoledronic acid (Zoledronate) is a new, potent third-generation bisphosphonate that has recently been approved by the U.S. Food and Drug Administration for the treatment of both osteolytic and osteoblastic bone metastases. A Phase 3 clinical trial comparing the efficacy of Zoledronic acid 4 and 8 mg compared with Pamidronate 90 mg every 3-4 weeks has been completed.
RESULTS
A 15 minute infusion of 4 mg of zoledronic acid is at least as effective as 90 mg of pamidronate in preventing skeletal complications in patients with metastatic breast cancer.
CONCLUSIONS
Bisphosphonate treatment can delay skeletal events in patients with breast carcinoma that is metastatic to bone. Future trials will build on the results achieved with bisphosphonate treatment.
Topics: Administration, Oral; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Forecasting; Glycoproteins; Humans; Imidazoles; Infusions, Intravenous; Osteoprotegerin; Pamidronate; Randomized Controlled Trials as Topic; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Zoledronic Acid
PubMed: 12548585
DOI: 10.1002/cncr.11123 -
Clinical Medicine & Research Jun 2017Sternocostoclavicular hyperostosis (SCCH) is an infrequent chronic inflammatory disorder of the axial skeleton of unknown origin. SCCH goes often unrecognized due to a...
Sternocostoclavicular hyperostosis (SCCH) is an infrequent chronic inflammatory disorder of the axial skeleton of unknown origin. SCCH goes often unrecognized due to a low level of awareness for the disorder. It typically presents with relapsing and remitting pain in the shoulder, neck, and anterior chest wall area with occasional swelling and tenderness of the sternoclavicular area. The diagnosis is confirmed radiologically by sclerosis and hyperostosis of the sternoclavicular joints. There have been several reports in which intravenous bisphosphonates and tumor necrosis factor-inhibitors have shown reasonable efficacy in the treatment of this disorder. We report a patient with a long history of SCCH in whom pamidronate 60 mg intravenously every 3 months for 3 years failed to reduce symptom severity and improve radiologic findings.
Topics: Adult; Diphosphonates; Female; Humans; Hyperostosis, Sternocostoclavicular; Pamidronate; Treatment Failure
PubMed: 28751466
DOI: 10.3121/cmr.2017.1352