Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis

Cutini, P.; Rauschemberger, María Belén; Sandoval, Marisa Julia; Massheimer, Virginia

doi:10.1016/j.yjmcc.2016.08.017

Cited by 26 publications

(25 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus N‐BPs have a cholesterol‐lowering effect . Bisphosphonates can also modulate ion channels in cardiac myocytes, regulate and inhibit vessel pathogenesis, and has an anti‐inflammatory effect . Animal studies have shown that N‐BPs attenuate diastolic dysfunction following MI, improve cardiac properties, and reduce severity of CVE …”

Section: Discussionmentioning

confidence: 99%

Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture

Sing

Wong

Kiel

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

The risk of cardiovascular events (CVEs) with alendronate use in real-world hip fracture patients is unknown. This study aimed to investigate the risk of CVE with and without use of alendronate in patients with hip fracture. We conducted a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with hip fracture from 2005 through 2013 were followed until November 6, 2016. Alendronate and other antiosteoporosis medications use during the study period were examined. We matched treated and nontreated patients based on time-dependent propensity score. The risks of cardiovascular mortality, myocardial infarction, and stroke between treatment groups were evaluated using conditional Cox regression stratified by match pairs. To examine the associations over time, outcomes were assessed at 1 year, 3 years, 5 years, and 10 years. Among 34,991 patients with newly diagnosed hip fracture, 4602 (13.2%) received antiosteoporosis treatment during follow-up. Physical functioning or survival prospect was not significantly different between treated and nontreated patients. A total of 4594 treated patients were matched with 13,568 nontreated patients. Results of Cox regression analysis revealed that alendronate was associated with a significantly lower risk of 1-year cardiovascular mortality (HR 0.33; 95% CI, 0.17 to 0.65) and incident myocardial infarction (HR 0.55; 95% CI, 0.34 to 0.89), whereas marginally significant reduction in risk of stroke was observed at 5 years and 10 years (HR at 5 years: 0.82; 95% CI, 0.67 to 1.00; p = 0.049; HR at 10 years: 0.83; 95% CI, 0.69 to 1.01; p = 0.065). The strength of the association declined over time but remained significant. Similar results were observed when all nitrogen-containing bisphosphonates (N-BPs) were analyzed together. These findings were robust in multiple sensitivity analyses. Additional studies in other population samples and randomized clinical trials may be warranted to further understand the relationship between use of various antiosteoporosis medication and risk of CVE in patients with hip fracture. © 2018 American Society for Bone and Mineral Research.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture

Sing

Wong

Kiel

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Multiple non-natural chemicals/medications also exhibit antioxidant properties and are effective against VC. We identified 19 types of such candidates with potential therapeutic effects against VC: acetylcysteine 33 , alendronate 49 , BMP inhibitor 39 , dimethyl fumarate 47 , farnesyltransferase inhibitor 41 , gemigliptin 57 , growth hormone-releasing hormone (GHRH) receptor agonist 58 , metformin 42 , pentoxifylline 64 , pravastatin 33 , pyrrolidine dithiocarbamate (PDTC) 34 , simvastatin 32 , sodium hydrosulfide 53 , sodium selenite 37,45 , STS 36,43,44 , Tempol 40 , TRAM-34 46 , topical poly(1,8-octamethylene-citrate-co-cysteine) (POCC) 54 , and hydrogen peroxide 51 . Among these, 11 (57.9%) were medications with specific clinical indications, while 8 (42.1%) were non-medicinal chemicals.…”

Section: Antioxidants Of Synthetic Origin or Pharmaceuticalsmentioning

confidence: 99%

“…Other medications, including anti-osteoporotic medication (alendronate), oral hypoglycemic agent (gemigliptin and metformin), hypolipidemic agents (pravastatin and simvastatin), medication for multiple sclerosis (dimethyl fumarate), microcirculatory insufficiency (pentoxifylline), and growth hormone deficiency (GHRH receptor agonist) have all been associated with suppressed ROS production and attenuated VC in different experimental models. Cutini et al showed that alendronate increased NO production and activated MAPK signaling pathway, while it attenuated inflammation and reduced VC severity 49 . Ha et al discovered that dimethyl fumarate administration led to Nrf2 activation, BMP-2 downregulation, and less severe VC in a calcified VSMC model and in animals with vitamin D-induced aortic calcification 47 .…”

Section: Antioxidants Of Synthetic Origin or Pharmaceuticalsmentioning

confidence: 99%

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

et al. 2019

View full text Add to dashboard Cite

Vascular calcification (VC) is highly prevalent in patients with advanced age, or those with chronic kidney disease and diabetes, accounting for substantial global cardiovascular burden. The pathophysiology of VC involves active mineral deposition by transdifferentiated vascular smooth muscle cells exhibiting osteoblast-like behavior, building upon cores with or without apoptotic bodies. Oxidative stress drives the progression of the cellular phenotypic switch and calcium deposition in the vascular wall. In this review, we discuss potential compounds that shield these cells from the detrimental influences of reactive oxygen species as promising treatment options for VC. A comprehensive summary of the current literature regarding antioxidants for VC is important, as no effective therapy is currently available for this disease. We systematically searched through the existing literature to identify original articles investigating traditional antioxidants and novel compounds with antioxidant properties with regard to their effectiveness against VC in experimental or clinical settings. We uncovered 36 compounds with antioxidant properties against VC pathology, involving mechanisms such as suppression of NADPH oxidase, BMP-2, and Wnt/β-catenin; anti-inflammation; and activation of Nrf2 pathways. Only two compounds have been tested clinically. These findings suggest that a considerable opportunity exists to harness these antioxidants for therapeutic use for VC. In order to achieve this goal, more translational studies are needed.

show abstract

“…Several potential mechanisms have been investigated, including reduction of serum low-density lipoproteins, halting of plaque formation, inhibition of vascular calcifications, and changes in circulating proinflammatory cytokines. (9)(10)(11)(12) We recently observed that N-BP may have anti-inflammatory and steroid-sparing properties in patients with polymyalgia rheumatica, a common inflammatory disorder. (13) Some years ago our group showed that N-BP could have an immunomodulatory effect on circulating gamma-delta (gd) T cells.…”

Section: To the Editormentioning

confidence: 99%

“…The physiopathology of decreased CV risk associated with N‐BP is poorly understood. Several potential mechanisms have been investigated, including reduction of serum low‐density lipoproteins, halting of plaque formation, inhibition of vascular calcifications, and changes in circulating proinflammatory cytokines …”

mentioning

confidence: 99%

Amino-Bisphosphonates and Cardiovascular Risk: A New Hypothesis Involving the Effects on Gamma-Delta T Cells

Giollo

Rossini

Gatti

et al. 2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Vascular action of bisphosphonates: In vitro effect of alendronate on the regulation of cellular events involved in vessel pathogenesis

Cited by 26 publications

References 44 publications

Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture

Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

Amino-Bisphosphonates and Cardiovascular Risk: A New Hypothesis Involving the Effects on Gamma-Delta T Cells

Contact Info

Product

Resources

About