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| zoledronic acid |
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| CHEBI:46557 |
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| An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position. |
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This entity has been manually annotated by the ChEBI Team.
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| ZINC000008551904 |
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more structures >>
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| Zoledronic acid, also known as zoledronate and sold under the brand name Zometa among others, by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due to cancer, Paget's disease of bone and Duchenne muscular dystrophy (DMD). It is given by injection into a vein.
Common side effects include fever, joint pain, high blood pressure, diarrhea, and feeling tired. Serious side effects may include kidney problems, low blood calcium, and osteonecrosis of the jaw. Use during pregnancy may result in harm to the baby. It is in the bisphosphonate family of medications. It works by blocking the activity of osteoclast cells and thus decreases the breakdown of bone.
Zoledronic acid was patented in 1986 and approved for medical use in the United States in 2001. It is on the World Health Organization's List of Essential Medicines. |
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Read full article at Wikipedia
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InChI=1S/C5H10N2O7P2/c8- 5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14) |
| XRASPMIURGNCCH-UHFFFAOYSA-N |
| OC(Cn1ccnc1)(P(O)(O)=O)P(O)(O)=O |
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bone density conservation agent
An agent that inhibits bone resorption and/or favor bone mineralization and bone regeneration. Used to heal bone fractures and to treat bone diseases such as osteopenia and osteoporosis.
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View more via ChEBI Ontology
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[1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid)
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zoledronic acid
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ChemIDplus
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(1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid
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ChemIDplus
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(1-hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid
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ChemIDplus
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ZOL
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DrugBank
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ZOLEDRONIC ACID
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PDBeChem
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2868
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DrugCentral
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61986
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ChemSpider
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D08689
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KEGG DRUG
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DB00399
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DrugBank
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US4939130
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Patent
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ZOL
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PDBeChem
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Zoledronic_acid
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Wikipedia
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| View more database links |
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118072-93-8
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CAS Registry Number
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DrugBank
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118072-93-8
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CAS Registry Number
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ChemIDplus
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118072-93-8
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CAS Registry Number
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KEGG DRUG
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2609374
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Gmelin Registry Number
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Gmelin
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9205049
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Beilstein Registry Number
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Beilstein
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Ureyen Ozdemir E, Adali E, Islimye Taskin M, Yavasoglu A, Aktug H, Oltulu F, Inceboz U (2022)
Effects of ranibizumab and zoledronic acid on endometriosis in a rat model.
Archives of gynecology and obstetrics 305, 267-274 [PubMed:34081204]
[show Abstract]
PurposeTo investigate the histological efficacy of ranibizumab and zoledronic acid in an experimentally induced endometriosis model as compared with danazol, buserelin acetate and dienogest.MethodsEndometrial implants were introduced in 52 female Wistar albino rats, which were then randomly divided into six groups. The animals were, respectively, given dienogest, danazol, buserelin acetate, zoledronic acid, ranibizumab and 0.9% NaCl. After 4 weeks, the volumes and histopathological properties of the implants were evaluated and the implants were excised completely at the third laparotomy. A histopathological scoring system was used to evaluate the preservation of epithelia. Endometrial explants were evaluated immunohistochemically.ResultsAmong the groups, the histological score was significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.001). There were no significant differences regarding ellipsoidal volume levels between groups (p > 0.05). However, there was a statistically significant difference regarding cell numbers according to the degree of Bcl-2, NF-κB, and CD31 staining (p < 0.001). There was no statistically significant difference in Bcl-2, CD31, or NF-κB staining in the binary comparisons between the other groups (p > 0.05). For Bcl-2 staining, the staining rate of the group treated with zoledronic acid was significantly lower compared with the dienogest and danazol groups (p < 0.05). The staining rates of CD31 and NF-κB were significantly lower in the zoledronic acid and ranibizumab groups compared with the controls (p < 0.05).ConclusionAccording to these results, zoledronic acid and ranibizumab may be putative candidates for the treatment of endometriosis. | Black DM, Reid IR, Napoli N, Ewing SK, Shiraki M, Nakamura T, Takeuchi Y, Schafer AL, Kim TY, Cauley JA (2022)
The Interaction of Acute-Phase Reaction and Efficacy for Osteoporosis After Zoledronic Acid: HORIZON Pivotal Fracture Trial.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 37, 21-28 [PubMed:34585443]
[show Abstract]
Zoledronic acid (ZOL) as a yearly infusion is effective in reducing fracture risk. An acute-phase reaction (APR), consisting of flu-like symptoms within 3 days after infusion, is commonly seen. The objective of this analysis was to investigate whether APR occurrence influences drug efficacy. This analysis uses data from the 3-year randomized clinical trial, Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT). APRs were identified as adverse events within 3 days of first infusion with higher frequency in ZOL than placebo. To compare mean 3-year change in bone mineral density (BMD) in ZOL versus placebo, among women with and without APR, t tests were used. Logistic regression was used to examine the relationship between APR occurrence and odds of incident morphometric vertebral fracture. Cox regression was used to determine the risk of nonvertebral and hip fractures for women with versus without APR. Logistic and Cox models were used to determine the risk of incident fracture in ZOL versus placebo for women with and without an APR. The analysis included 3862 women in the ZOL group and 3852 in placebo, with 42.4% in ZOL versus 11.8% in placebo experiencing an APR. The difference in BMD mean change for ZOL versus placebo was similar for women with and without an APR (all p interaction >0.10). Among ZOL women, those with APR had 51% lower vertebral fracture risk than those without (odds ratio [OR] = 0.49, p < 0.001). A similar but nonsignificant trend was observed for nonvertebral and hip fracture (relative hazard [RH] = 0.82, p = 0.10; RH = 0.70, p = 0.22, respectively). There was a greater treatment-related reduction in vertebral fracture risk among women with APR (OR = 0.19) than those without (OR = 0.38) (p interaction = 0.01). Our results suggest that women starting ZOL who experience an APR will have a larger reduction in vertebral fracture risk with ZOL. © 2021 American Society for Bone and Mineral Research (ASBMR). | Yu Y, Liang C, Xu R, Wang T, Deng F, Yu X (2022)
Titanium implant alters the effect of zoledronic acid on the behaviour of endothelial cells.
Oral diseases 28, 1968-1978 [PubMed:33908127]
[show Abstract]
ObjectivesTo evaluate the effect of zoledronic acid (ZA) on human umbilical vein endothelial cells (HUVECs) attached to different surfaces.Materials and methodsA total of three groups were evaluated in this study: sandblasting and acid etching (SLA) + HUVECs; mechanically polished (MP) + HUVECs; and plastic cell culture plates + HUVECs. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, surface roughness and water contact angle were tested for titanium surface characterisation. ZA was added at different concentrations (0, 1, 10, 50 and 100 μM). Cell adhesion, proliferation, viability, apoptosis and gene expression were evaluated.ResultsMechanically polished and SLA surfaces showed negative effects on cell adhesion and proliferation and promoted cell apoptosis with 100 μM ZA (p < .05). The highest expression of intercellular adhesion molecule-1 (ICAM-1) and angiopoietin-1 was found on SLA surfaces (p < .01). The lowest expression of platelet-endothelial cell adhesion molecule-1 and ICAM-1 was found on MP surfaces (p < .05). A significant decrease in von Willebrand factor was detected on MP and SLA surfaces (p < .001).ConclusionsZoledronic acid has an anti-angiogenic effect on HUVECs attached to titanium implants, while the SLA surface might stimulate HUVECs to express angiogenic and adhesive factor genes despite ZA treatment. | Churilla BM, Perera S, Greenspan SL, Resnick NM, Kotlarczyk MP (2022)
Zoledronic acid and bone health in older adults with cognitive impairment.
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 33, 293-298 [PubMed:34341833]
[show Abstract]
Fracture prevention in cognitively impaired individuals is lacking. This work highlights the benefits of zoledronic acid on bone health in cognitively impaired older adults. Demonstrating benefits of therapy may increase treatment uptake and reduce fracture risk in this group.IntroductionOsteoporosis has detrimental consequences for frail older adults. The effects on those with both osteoporosis and cognitive impairment are compounded due to increased risk of falls and changes in mobility, both of which can lead to fracture. However, there are limited data on treatment benefits for osteoporotic individuals with cognitive impairment.MethodsThis post hoc, secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of single-dose zoledronic acid included 179 women age ≥ 65 years residing in assisted living facilities or nursing homes, 43 of whom had mild to severe cognitive impairment. We assessed bone mineral density (BMD) of the total hip, femoral neck, and lumbar spine by dual-energy x-ray absorptiometry and serum bone turnover markers (C-terminal telopeptide of type I collagen and procollagen type I N propeptide) at 6 and 12 months.ResultsIn participants with cognitive impairment, those who received zoledronic acid had 4.3% greater BMD at the total hip (p=.005) and 5.3% greater BMD at the femoral neck (p<.001) after 12 months compared to those in the placebo group. Bone turnover markers demonstrated significant decreases at 6 months in those with cognitive impairment who received active treatment compared to the placebo group. Improvements in bone health measures with zoledronic acid were similar to those seen in participants without cognitive impairment.ConclusionZoledronic acid improves bone health in frail older women with cognitive impairment similar to those without impairment. Further studies are warranted to assess the benefit for fracture reduction in this undertreated population. | Sokmen N, Dundar S, Bozoglan A, Yildirim TT, Sokmen K, Sayeste E, Isayev A, Kirtay M (2022)
Effect of Primary Stabilisation on Osseointegration of Implants With Local and Systemic Zoledronic Acid Application.
The Journal of craniofacial surgery 33, 1276-1281 [PubMed:34560734]
[show Abstract]
AbstractPrimary stabilization (PS) is defined as initial tight fit during the surgical placement of an implant. Tight implant placement is quite difficult in cases where bone quality and quantity are insufficient. Zoledronic acid (ZA) is a powerful bisphosphonate that prevents bone resorption. The aim of this study is to investigate the effect of local and systemic ZA application on osseointegration in titanium implants with and without PS. Male Sprague Dawley rats were divided into 2 main groups, with PS, PS + (n = 24), and without primary stabilisation, PS - (n = 24). These main groups were divided into control (n = 8), 2mg/1 mL local ZA (n = 8) and 0.1mg/kg systemic ZA (n = 8) groups. All of the subjects were sacrificed after a 4-week recovery period. Bone implant connection (BiC) and thread filling (TF) (%) of the samples was analyzed according to the non-decalcified histological analysis method. In terms of BiC percentages and TF, statistically significant differences were found between the groups with and without PS and between the ZA treatment groups ( P < 0.05). The common effect of PS and ZA use on the percentage of BIC was found to be statistically significant ( P < 0.05). The common effect of PS and acid type on TF was not statistically significant ( P < 0.05). Within the limitations of this study, it may be concluded that systemic and local administration of ZA may increase implant osseointegration. | Khalid MF, Micieli J (2021)
Zoledronic acid-induced orbital inflammation.
BMJ case reports 14, e245359 [PubMed:34413050] | Alsalih A, Dam A, Lindberg P, Truedsson A (2021)
Medication-Related Osteonecrosis of the Jaws Initiated by Zoledronic Acid and Potential Pathophysiology.
Dentistry journal 9, 85 [PubMed:34435997]
[show Abstract]
The aim of this systematic review is to present an up-to-date review of available publications investigating the cellular mechanisms initiating the development of medication-related osteonecrosis of the jaw caused by zoledronic acid. Electronic searches of MEDLINE/PubMed and Scopus were conducted on the 3 June 2019. A total of 804 publications were identified, of which 11 met the inclusion criteria and were, therefore, included in this study. All the included studies were in vitro studies investigating various human cells. The current review found that zoledronic acid in various concentrations increased apoptosis and decreased migration and proliferation of epithelial cells, fibroblasts, osteoblasts, endothelial cells and dental pulp stem cells, which can affect local tissue homeostasis. The consequences of zoledronic acid were found to be both time- and dose-dependent. The pathophysiology of medication-related osteonecrosis of the jaw is likely a multifactorial process involving prolonged wound healing, chronic inflammation and altered bone remodelling following the administration of zoledronic acid. Further research is needed to identify the exact pathophysiology to optimise management and treatment. | Huang CF, Shiao MS, Mao TY (2021)
Retrospective Study of the Effects of Zoledronic Acid on Muscle Mass in Osteoporosis Patients.
Drug design, development and therapy 15, 3711-3715 [PubMed:34475752]
[show Abstract]
PurposeSeveral osteoporosis drugs can continuously improve bone mass, but the impact on muscle mass is still unknown. This study aims to investigate how zoledronic acid monotherapy affected muscle mass in osteoporosis patients.Patients and methodsPatients from an osteoporosis database were divided into two groups in this retrospective cohort, case-control study: zoledronic acid-treated patients (n = 113) and a control group without osteoporosis treatment (n = 118). At four years, appendicular skeletal muscle mass (ASM) and appendicular skeletal muscle mass index (ASMI) were calculated using dual-energy X-ray absorptiometry. The differences in muscle mass between the groups were compared.ResultsAt baseline, there was no difference in sex, ASM, ASMI, and bone mineral density between the zoledronic acid treatment group and the control group. The treatment group's skeletal muscle mass increased by 841 g in ASM and 0.35 kg/m2 in ASMI after three years, while decreased in the control group.ConclusionThis study for the first time demonstrated that that zoledronic acid is beneficial not only to the bone but also to muscle. | Ryhänen EM, Koski AM, Löyttyniemi E, Välimäki MJ, Kiviniemi U, Schalin-Jäntti C (2021)
Postoperative zoledronic acid for osteoporosis in primary hyperparathyroidism: a randomized placebo-controlled study.
European journal of endocrinology 185, 515-524 [PubMed:34324430]
[show Abstract]
ObjectiveIn primary hyperparathyroidism (PHPT) with osteoporosis, bone mineral density (BMD) improves after parathyroidectomy. It is unclear whether combining surgery with postoperative bisphosphonate treatment can further improve bone health.DesignThis randomized, placebo-controlled study compared the effects of surgery alone and surgery combined with zoledronic acid on bone metabolism in PHPT with osteoporosis.MethodsFifty-six patients (f/m 47/9, mean age 68.4 years) with PHPT and osteoporosis were randomized 1-3 months after parathyroidectomy to receive a 2-year treatment of zoledronic acid or placebo. Dual-energy X-ray absorptiometry (DXA) and bone turnover markers (N-terminal propeptide of type 1 procollagen, C-terminal telopeptide of type 1 collagen, and alkaline phosphatase) were measured annually during the 2-year follow-up.ResultsTwo years after parathyroidectomy, BMD was significantly higher in the zoledronic acid (ZOL) group compared with the placebo (PBO) group at the femoral neck (P = 0.045 for Z-score) and lumbar spine (P = 0.039 and 0.017 for T- and Z-scores, respectively). Bone turnover markers were significantly lower in the ZOL group (P < 0.001 for all markers). Of the 18 patients who had received bisphosphonates for >1 year before surgery, BMD improved significantly in the ZOL group both in the femoral neck and lumbar spine (n = 10; all P < 0.001-0.01), but in the PBO group, only in the lumbar spine (n = 8, P = 0.03), (P = 0.08-0.95 for between-group changes).ConclusionBMD increases after parathyroidectomy both with and without zoledronic acid but the increase is significantly higher with postoperative zoledronic acid. | Wang X, Su P, Kang Y, Xu C, Qiu J, Wu J, Sheng P, Huang D, Zhang Z (2021)
Combination of Melatonin and Zoledronic Acid Suppressed the Giant Cell Tumor of Bone in vitro and in vivo.
Frontiers in cell and developmental biology 9, 690502 [PubMed:34447747]
[show Abstract]
Melatonin (Mlt) confers potential antitumor effects in various types of cancer. However, to the best of our knowledge, the role of Mlt in the giant cell tumor of bone (GCTB) remains unknown. Moreover, further research is required to assess whether Mlt can enhance the therapeutic effect of zoledronic acid (Zol), a commonly used anti-GCTB drug. In this research, we investigated the effects of Mlt, Zol, and the combination of these two drugs on GCTB cells' characteristics, including cell proliferation, apoptosis, osteogenic differentiation, migration, and invasion. The cell counting kit-8 (CCK-8) assay, colony formation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL), alkaline phosphatase (ALP) staining, alizarin red staining (ARS), scratch wound healing assay, and transwell experiment were performed, respectively. Our results showed that Mlt could effectively inhibit the proliferation, migration, and invasion of GCTB cells, as well as promote the apoptosis and osteogenic differentiation of tumor cells. Of note, a stronger antitumor effect was observed when Mlt was combined with Zol treatment. This therapeutic effect might be achieved by inhibiting the activation of both the Hippo and NF-κB pathways. In conclusion, our study suggests that Mlt can be a new treatment for GCTB, which could further enhance the antitumor effect of Zol. | Mochizuki T, Yano K, Ikari K, Okazaki K (2021)
Safety and Efficacy of Zoledronic Acid Treatment with and without Acetaminophen and Eldecalcitol for Osteoporosis.
Internal medicine (Tokyo, Japan) 60, 2585-2591 [PubMed:34393156]
[show Abstract]
Objectives We aimed to investigate the safety of zoledronic acid (ZOL) combined with acetaminophen (APAP) regarding both the adverse events and the efficacy of ZOL combined with an eldecalcitol (ELD) in a randomized clinical trial conducted in patients with primary osteoporosis. Methods A total of 109 patients were administered ZOL 5 mg and then were randomly assigned to the following groups (3:2:1): those treated with ZOL, those treated with ZOL combined with APAP and ELD, and those treated with ZOL combined with ELD. For the analyses, the groups were classified into four treatment groups: patients treated with APAP (APAP group) and without APAP (non-APAP group), and those treated with ELD (ELD group) and without ELD (non-ELD group). The incidence rates of symptomatic adverse events were compared between the APAP and non-APAP groups, and the efficacy was compared between the ELD and non-ELD groups. Results In the APAP and non-APAP groups, the incidence rates of symptomatic adverse events were 20.6% and 44.6% (p=0.009), respectively. Age and APAP use were found to be significant factors associated with adverse events. The percent changes in the bone mineral density values from baseline (ΔBMD) in the ELD and non-ELD groups at 12 months were 8.2% and 6.2% for the lumbar spine, 4.2% and 4.0% for the total hip, and 3.9% and 2.2% for the femoral neck, respectively. The ΔBMD of all sites did not differ significantly between the ELD and non-ELD groups. Conclusion In ZOL treatment, the co-administration of APAP should thus be considered as a therapeutic option to reduce the occurrence of symptomatic adverse events stemming from ZOL treatment in Japanese patients with primary osteoporosis, particularly in younger patients. | Küçüktürkmen B, Öz UC, Toptaş M, Devrim B, Saka OM, Bilgili H, Deveci MS, Ünsal E, Bozkır A (2021)
Development of Zoledronic Acid Containing Biomaterials for Enhanced Guided Bone Regeneration.
Journal of pharmaceutical sciences 110, 3200-3207 [PubMed:33984339]
[show Abstract]
In recent years, biomaterial-based treatments, also called guided bone regeneration (GBR), which aim to establish a bone regeneration site and prevent the migration of gingival connective tissue and / or peripheral epithelium through the defective area during periodontal surgical procedures have come to the fore. In this report, we have developed a nanoparticle bearing thermosensitive in situ gel formulation of Pluronic F127 and poly(D,L-lactic acid) based membrane to reveal their utilization at GBR by in-vivo applications. In addition, the encouragement of the bone formation in defect area via inhibition of osteoclastic activity is intended by fabrication these biodegradable biomaterials at a lowered Zoledronic Acid (ZA) dose. Both of the developed materials remained stable under specified stability conditions (25 °C, 6 months) and provided the extended release profile of ZA. The in-vivo efficacy of nanoparticle bearing in situ gel formulation, membrane formulation and simultaneous application for guided bone regeneration was investigated in New Zealand female rabbits with a critical size defect of 0.5 × 0.5 cm in the tibia bone for eight weeks. Based on the histopathological findings, lamellar bone and primarily woven bone formations were observed after 8 weeks of post-implantation of both formulations, while fibrosis was detected only in the untreated group. Lamellar bone growth was remarkably achieved just four weeks after the simultaneous application of formulations. Consequently, the simultaneous application of ZA-membrane and ZA-nanoparticles loaded in-situ gel formulations offers enhanced and faster GBR therapy alternatives. | Betlachin A, Grock S, Ahmadi S (2021)
Severe Hypophosphatemia and Elevated FGF23 Level Following Zoledronic Acid Infusion
Journal of the Endocrine Society 5, A220-A221 [PubMed Central:PMC8090009]
[show Abstract]
Abstract Background: Severe hypophosphatemia may be seen following zoledronic acid infusion, however FGF23 elevation has not been previously reported. Clinical Case: A 67-year-old man with Crohn’s disease status post remote ileocolonic resection, malnutrition (BMI 16.7), anemia, history of hypovitaminosis D, secondary hyperparathyroidism, and severe osteoporosis, was advised to present to the emergency room for hypocalcemia and hypophosphatemia after routine lab draw. His initial ionized calcium was 0.89 mmol/L (1.09–1.29 mmol/L) and phosphorus was 0.9 mg/dL (2.3–4.4 mg/dL), with a 25-hydroxyvitamin D level of 62 ng/mL (20–50 ng/mL), PTH of 132 pg/mL (11–51 pg/mL), and normal renal function. Hemoglobin was stable between 8–9 g/dL (13.5–17.1 g/dL). He endorsed ongoing fatigue, oral ulcers, and perioral numbness, which had been attributed to Humira infusion 2 months prior. He denied other paresthesias, carpopedal spasms, seizures, bone pain, or confusion. He reported receiving his second annual infusion of zoledronic acid 10 days prior in Turkey. He was started on high-dose oral calcium, calcitriol, and phosphate, which were continued on discharge 5 days later. Several days into his hospitalization, the patient spoke with his wife in Turkey who confirmed that his calcium and phosphorus were both within normal limits immediately prior to his infusion. A 1,25-hydroxyvitamin D level obtained during his workup was normal at 42.5 pg/mL (19.9–79.3 pg/mL), however an FGF23 level, which returned 2 weeks later, was elevated at 287 RU/mL (<=180 RU/mL). Dotatate PET to rule out oncogenic osteomalacia was negative. One month later, after normalization of calcium and phosphorus levels, repeat PTH and FGF23 levels were both within normal limits. Conclusion: This case demonstrates that a transient increase in FGF23 levels may accompany and exacerbate hypophosphatemia following zoledronic acid infusion. The mechanism for this elevation is unclear, though we speculate that in the setting of acute hypocalcemia and hypophosphatemia due to zoledronic acid infusion, secondary hyperparathyroidism may upregulate FGF23 production, which further decreases phosphorus levels. If this scenario is accurate, the transient FGF23 elevation seen is not pathologic, but physiologic. Indeed, in the patient above, calcium and phosphorus repletion lead to normalization of both PTH and FGF23. | Amro A, Ratrout S, Asfour F (2021)
Voltametric Determination of Zoledronic Acid in a Pharmaceutical Formulation
Turkish journal of pharmaceutical sciences 18, 339-343 [PubMed:34157824]
[show Abstract]
ObjectivesThe aim of this study is to study the electroactivity of zoledronic acid (ZOL), optimize the parameters affecting voltametric analysis of ZOL, and make a comparison between voltametric methods used to assay ZOL.Materials and methodsThree voltametric methods, cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV), were used to determine the concentrations of ZOL solutions (0.25-1.2 mg.mL-1). Britton-Robinson universal buffer solutions (BRB) were used as supporting electrolytes with a glassy carbon working electrode.ResultsThe calibration plots were linear in the range from 0.20 to 1.2 mg.mL-1 for differential DPV and CV and from 0.09 to 1.2 mg.mL-1 for SWV. DPV showed the highest correlation coefficient R2 value of 0.993 and the lowest limit of detection (LOD) of 37.2 μg.mL-1. Furthermore, DPV exhibited the highest precision with the lowest relative standard deviations (RSD) values. For a commercial product of ZOL, DPV showed the best accuracy and precision with 102.32% recovery and 2.88% RSD.ConclusionZOL is an electroactive compound. The pH of the BRB supporting the electrolyte is important for ZOL electroactivity. DPV is the recommended method for voltametric analysis of ZOL because of its high-performance regarding accuracy, precision, and LOD compared with other studied methods. | Doggrell SA (2009)
Is zoledronic acid an anticancer drug?
Expert opinion on pharmacotherapy 10, 2387-2390 [PubMed:19751105] | Lambrinoudaki I, Vlachou S, Galapi F, Papadimitriou D, Papadias K (2008)
Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women.
Clinical interventions in aging 3, 445-451 [PubMed:18982915]
[show Abstract]
Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. Zoledronic acid is an antiresorptive agent which has a high affinity for mineralized bone and especially for sites of high bone turnover. Zoledronic acid is excreted by the kidney without further metabolism. Zoledronic acid administered as a 5 mg intravenous infusion annually increases bone mineral density in the lumbar spine and femoral neck by 6.7% and 5.1% respectively and reduces the incidence of new vertebral and hip fractures by 70% and 41% respectively in postmenopausal women with osteoporosis. Most common side effects are post-dose fever, flu-like symptoms, myalgia, arthralgia, and headache which usually occur in the first 3 days after infusion and are self-limited. Rare adverse effects include renal dysfunction, hypocalcemia, atrial fibrillation, and osteonecrosis of the jaw. | Yuasa T, Kimura S, Ashihara E, Habuchi T, Maekawa T (2007)
Zoledronic acid - a multiplicity of anti-cancer action.
Current medicinal chemistry 14, 2126-2135 [PubMed:17691952]
[show Abstract]
Bisphosphonates (BPs) are inhibitors of bone-resorption and have become the current standard of care for preventing skeletal complications associated with bone metastases. Among BPs, zoledronic acid (ZOL) has the strongest activity of anti-bone resorption and shows diverse direct anti-cancer effects in vitro. Some chemical and biological characteristics of ZOL indicate the potential for in vivo growth inhibition and the mechanisms responsible for the observed anti-cancer effects are beginning to be elucidated. ZOL inhibits farnesyl pyrophosphate synthase, a key enzyme in the mevalonate pathway. Consequently, it inhibits the prenylation of small G-proteins such as Ras, Rap1, Rho and Rab, reduces the signals they mediate, and thereby prevents the growth, adhesion/spreading, and invasion of cancer cells. ZOL, which has a high affinity for mineralized bone, rapidly localizes to bone, resulting in therapeutically effective local concentrations for the cancer cells in bone. ZOL also blocks osteolysis and osteoclastgenesis, thus preventing the release of various growth factors which are abundantly stored in bone. Moreover, ZOL stimulates gammadelta T cells, which play important roles in innate immunity against cancer. In addition, ZOL is also a potent inhibitor of angiogenesis, probably due to the modification of various angiogenic properties of endothelial cells. Furthermore, ZOL synergizes with a variety of anticancer agents including chemotherapeutic drugs, molecular targeted agents, and other biological agents. Based on these potential anti-cancer properties, several clinical trials have been initiated to test the combination of ZOL and other agents. The accumulated encouraging evidence to date indicate that ZOL is an attractive anti-cancer agent which promises to be the next exciting therapy for patients with various cancers. | Saad F, McKiernan J, Eastham J (2006)
Rationale for zoledronic acid therapy in men with hormone-sensitive prostate cancer with or without bone metastasis.
Urologic oncology 24, 4-12 [PubMed:16414486]
[show Abstract]
Men with prostate cancer are at risk for bone loss and skeletal complications throughout the course of their disease. Bone loss is prevalent in many men with prostate cancer at initial diagnosis, and initiating androgen deprivation therapy results in accelerated bone resorption, leading to bone loss and an increased risk of fracture. These men are also at high risk for disease progression and bone metastases that can result in significant skeletal morbidity, including pathologic fracture, spinal cord compression, and debilitating bone pain requiring additional therapy. Excessive osteoclast activity plays a central role in the pathophysiology of bone disease at each stage of prostate cancer disease progression. Zoledronic acid, a highly potent inhibitor of osteoclast-mediated bone resorption, has increased bone mineral density in men receiving androgen deprivation therapy and is the only bisphosphonate that has shown statistically significant reductions in skeletal morbidity in patients with bone metastases from prostate cancer. Furthermore, preclinical evidence suggests that zoledronic acid has antitumor activity in prostate cancer models. Recently, a treatment algorithm was developed by the 3rd International Consultation on Prostate Cancer recommending the use of zoledronic acid for the prevention of skeletal complications in patients with bone metastases from prostate cancer, regardless of their hormone status, and for the prevention of treatment-induced bone loss in patients without evidence of bone metastases. According to this algorithm, zoledronic acid should be considered for the prevention of skeletal morbidity in patients with prostate cancer throughout their treatment continuum. | Perry CM, Figgitt DP (2004)
Zoledronic acid: a review of its use in patients with advanced cancer.
Drugs 64, 1197-1211 [PubMed:15161327]
[show Abstract]
Zoledronic acid (Zometa), a parenteral bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption and is used in the management of patients with cancer. Zoledronic acid 4 mg is administered as an intravenous infusion over 15 minutes. In the treatment of bone metastases, zoledronic acid is the first and only bisphosphonate to demonstrate efficacy in patients with a broad range of tumour types and in multiple myeloma. In well-designed trials, a single 4 mg dose of zoledronic acid showed good efficacy in the treatment of patients with hypercalcaemia of malignancy. Zoledronic acid 4 mg was superior to pamidronic acid 90 mg, administered as a 2-hour infusion, as assessed by normalised serum calcium concentrations 10 days after administration. In conjunction with antineoplastic therapy, zoledronic acid was an effective long-term (up to 25 months) treatment for skeletal-related events in patients with bone metastases associated with multiple myeloma or solid tumours. In patients with bone metastases secondary to breast cancer or bone lesions from myeloma, zoledronic acid was at least as effective as pamidronic acid, based on assessments of skeletal-related events 25 months after the start of treatment. In addition, compared with pamidronic acid, the overall risk of developing skeletal complications, including hypercalcaemia of malignancy, was significantly reduced in recipients of zoledronic acid. Compared with pamidronic acid, zoledronic acid reduced the risk of patients with breast cancer developing a skeletal-related event by an additional 20%. Zoledronic acid was significantly more effective than placebo on most efficacy measures in patients with bone metastases secondary to other solid tumours (e.g. lung, prostate) and showed sustained efficacy for up to 15 months. Preliminary data indicate that its efficacy in these patients is sustained for up to 24 months. Estimates of the cost effectiveness of zoledronic acid in the treatment of prostate cancer were consistent with those of other bisphosphonates, and cost-effectiveness ratios were within limits considered acceptable economic value. Zoledronic acid was generally well tolerated, with a tolerability profile similar to that of pamidronic acid and placebo. As with other bisphosphonates, deterioration of renal function has occasionally been reported in patients receiving zoledronic acid and monitoring of serum creatinine is recommended during treatment. The efficacy of zoledronic acid is therefore well established in patients with hypercalcaemia of malignancy and, for up to 25 months, in the treatment of complications arising from metastatic bone disease in patients with multiple myeloma or solid tumours. The clinical profile of zoledronic acid compares favourably with that of pamidronic acid in patients with cancer and zoledronic acid has a more convenient administration schedule with the potential for better compliance. Thus, zoledronic acid is an effective bisphosphonate and is positioned to play an important role in the management of advanced cancer patients with bone metastases. | Chaplet M, Detry C, Deroanne C, Fisher LW, Castronovo V, Bellahcéne A (2004)
Zoledronic acid up-regulates bone sialoprotein expression in osteoblastic cells through Rho GTPase inhibition.
The Biochemical journal 384, 591-598 [PubMed:15324309]
[show Abstract]
Clinical practice reveals that osteoporotic women treated with BPs (bisphosphonates) show an increased bone mass density and a reduced risk of fractures. However, the mechanisms leading to these beneficial effects of BPs are still poorly understood. We hypothesized that ZOL (zoledronic acid), a potent third-generation BP, may induce the expression of proteins associated with the bone-forming potential of osteoblastic cells such as BSP (bone sialo-protein). Expression of BSP gene is up-regulated by hormones that promote bone formation and has been associated with de novo bone mineralization. Using real-time reverse transcriptase-PCR and Western-blot analysis, we demonstrated that ZOL increased BSP expression in Saos-2 osteoblast-like cells. Nuclear run-on and mRNA decay assays showed no effect at the transcriptional level but a stabilization of BSP transcripts in ZOL-treated cells. ZOL effect on BSP expression occurred through an interference with the mevalonate pathway since it was reversed by either mevalonate pathway intermediates or a Rho GTPase activator. We showed that ZOL impaired membrane localization of RhoA in Saos-2 cells indicating reduced prenylation of this protein. By the use of small interfering RNAs directed to RhoA and Rac1, we identified both Rho GTPases as negative regulators of BSP expression in Saos-2 cells. Our study demonstrates that ZOL induces BSP expression in osteoblast-like cells through inactivation of Rho GTPases and provides a potential mechanism to explain the favourable effects of ZOL treatment on bone mass and integrity. | Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM, Castronovo V, Green JR (2002)
Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.
The Journal of pharmacology and experimental therapeutics 302, 1055-1061 [PubMed:12183663]
[show Abstract]
Bisphosphonate drugs inhibit osteoclastic bone resorption and are widely used to treat skeletal complications in patients with tumor-induced osteolysis. We now show that zoledronic acid, a new generation bisphosphonate with a heterocyclic imidazole substituent, is also a potent inhibitor of angiogenesis. In vitro, zoledronic acid inhibits proliferation of human endothelial cells stimulated with fetal calf serum, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (IC(50) values 4.1, 4.2, and 6.9 microM, respectively), and modulates endothelial cell adhesion and migration. In cultured aortic rings and in the chicken egg chorioallantoic membrane assay, zoledronic acid reduces vessel sprouting. When administered systemically to mice, zoledronic acid potently inhibits the angiogenesis induced by subcutaneous implants impregnated with bFGF [ED(50), 3 microg/kg (7.5 nmol/kg) s.c.]. These findings indicate that zoledronic acid has marked antiangiogenic properties that could augment its efficacy in the treatment of malignant bone disease and extend its potential clinical use to other diseases with an angiogenic component. |
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