scholarly journals Zoledronic acid increases the prevalence of medication-related osteonecrosis of the jaw in a dose dependent manner in rice rats (Oryzomys palustris) with localized periodontitis

Bone ◽  
2018 ◽  
Vol 108 ◽  
pp. 79-88 ◽  
Author(s):  
J.G. Messer ◽  
J.L. Mendieta Calle ◽  
J.M. Jiron ◽  
E.J. Castillo ◽  
C. Van Poznak ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Osteonecrosis Of The Jaw ◽  
Dependent Manner ◽  
Oryzomys Palustris ◽  
Dose Dependent

Zoledronic Acid Deteriorates Soft and Hard Tissue Healing of Murine Tooth Extraction Sockets in a Dose-Dependent Manner

2021 ◽  
Author(s):  
Ryohei Kozutsumi ◽  
Shinichiro Kuroshima ◽  
Haruka Kaneko ◽  
Muneteru Sasaki ◽  
Akira Ishisaki ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Tooth Extraction ◽  
Dependent Manner ◽  
Hard Tissue ◽  
Tissue Healing ◽  
Dose Dependent

Zoledronic Acid Inhibits Osteoclastogenesis in Vitro and in a Mouse Model of Inflammatory Osteolysis

2003 ◽  
Vol 112 (9) ◽  
pp. 780-786 ◽  
Author(s):  
Holger Sudhoff ◽  
Brian T. Faddis ◽  
Jae Y. Jung ◽  
Henning Hildmann ◽  
Jörg Ebmeyer ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Marrow Cells ◽  
Mineral Apposition Rate ◽  
Tunel Staining ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Dependent Manner ◽  
Dose Dependent

This study assessed effects of the bisphosphonate zoledronic acid (ZLNA) on osteoclastogenesis. To assess the effect of ZLNA on osteoclast formation in vitro, we cultured mouse bone marrow cells under conditions that promote osteoclastogenesis. Administered at concentrations from 10−6 to 10−9 mol/L, ZLNA led to a dose-dependent inhibition of osteoclastogenesis. Combined TUNEL staining and histochemical staining for tartrate-resistant acid phosphatase showed that ZLNA induced apoptosis in osteoclasts and monocytic precursor cells. To study the effects of ZLNA in vivo, we placed keratin particles onto the surface of the parietal bone of mice to induce localized inflammatory bone resorption. Three experimental groups received daily subcutaneous injections of ZLNA (1, 3, or 10 μg/kg body weight) from 4 days before surgery until 5 days after keratin implantation. The ZLNA significantly reduced osteoclast recruitment in a dose-dependent manner, but did not affect the degree of inflammation or the mineral apposition rate.

scholarly journals Medication-Related Osteonecrosis of the Jaws Initiated by Zoledronic Acid and Potential Pathophysiology

2021 ◽  
Vol 9 (8) ◽  
pp. 85
Author(s):  
Aya Alsalih ◽  
Annica Dam ◽  
Pia Lindberg ◽  
Anna Truedsson
Keyword(s):  
Zoledronic Acid ◽  
Dental Pulp ◽  
Bone Remodelling ◽  
Osteonecrosis Of The Jaw ◽  
Inclusion Criteria ◽  
Cellular Mechanisms ◽  
Osteonecrosis Of The Jaws ◽  
Current Review ◽  
Dose Dependent

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.

scholarly journals Prevalence of bisphosphonate-related osteonecrosis of the jaw-like lesions is increased in a chemotherapeutic dose-dependent manner in mice

Bone ◽  
2018 ◽  
Vol 112 ◽  
pp. 177-186 ◽  
Author(s):  
Shinichiro Kuroshima ◽  
Muneteru Sasaki ◽  
Kazunori Nakajima ◽  
Saki Tamaki ◽  
Hiroki Hayano ◽  
...  
Keyword(s):  
Osteonecrosis Of The Jaw ◽  
Dependent Manner ◽  
Dose Dependent

Zoledronic acid induces anti-cancer effects on prostate cancer cells through the modulation of the angiogenesis associated CYR61 and the androgen-differentiation associated NDRG-1 genes

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21079-21079
Author(s):  
G. Tonini ◽  
B. Vincenzi ◽  
M. Marra ◽  
A. Baldi ◽  
S. Addeo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
The Other ◽  
Cytotoxic Agents ◽  
Dependent Manner ◽  
Other Hand ◽  
Anti Cancer ◽  
Pc3 Cells ◽  
Upregulated Genes ◽  
Dose Dependent

21079 Background: Aminobisphosphonates (ABPs) has a definite direct anti-tumour activity but a limited activity in vivo. Their molecular targets are still not completely defined. Therefore, we have studied the effects of zoledronic acid (ZOL) addition to prostate cancer PC3 cells on gene expression profile. Methods: We have treated PC3 cells with 100 μM ZOL for 24 hours, extracted mRNAs and probed on Affimetrix HG-U133. Thereafter, we have identified down modulated and upregulated genes and checked for modulation of mRNA with RT PCR and of the relative encoded proteins with western blotting. Results: We have found 6 down modulated and 32 upregulated genes. We have focused our attention on NDRG1 associated to the androgen-differentiation and on Cysteine rich 61 (CYR61) involved in the regulation of proliferation and angiogenesis. NDRG1 mRNA was up-regulated and CYR61 mRNA was downregulated by ZOL in a dose-dependent manner. Similar effects were observed at protein product levels with an about 2-fold change recorded already in cells treated with 50 μM ZOL. Interestingly, also Gefitinib, Sorafenib and Tipifarnib used at their IC:50s could induce changes in both NDRG1 and CYR61 expression, but 50 μM ZOL was about 2-fold more potent. On the other hand, cytotoxic agents such as docetaxel did not have any effect. The addition of farnesol (FOH) or geranylgeraniol (GGOH) to ZOL-treated cells was able to counteract the effect of ZOL on CYR61 expression partially or completely, respectively. On the other hand, both FOH and GGOH had poor effect on the regulation of NDRG1 expression induced by ZOL. Conclusions: ZOL induces a strong regulation of the expression of NDRG1 and CYR61 at both mRNA and protein levels that appears to be dose-dependent and specific. CYR61 modulation seems to be more dependent from the inhibition of geranylgeranylation processes while NDRG1 changes could be at least in part independent from the inhibition of isoprenylation induced by ZOL. The study of the biological relevance of these effects on the anti-cancer effects of ZOL is ongoing with small interference RNA approaches. No significant financial relationships to disclose.

scholarly journals Oncologic doses of zoledronic acid induce osteonecrosis of the jaw-like lesions in rice rats (Oryzomys palustris) with periodontitis

2012 ◽  
Vol 27 (10) ◽  
pp. 2130-2143 ◽  
Author(s):  
J Ignacio Aguirre ◽  
Mohammed P Akhter ◽  
Donald B Kimmel ◽  
Jennifer E Pingel ◽  
Alyssa Williams ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Osteonecrosis Of The Jaw ◽  
Oryzomys Palustris

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

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