Influence of zoledronic acid on proliferation, migration, and apoptosis of vascular endothelial cells

Lang, Miaojie; Zhou, Zhenhua; Shi, Lu; Niu, Jianlou; Xu, Shengwen; Lin, Weihong; Chen, Z.; Wang, Y.

doi:10.1016/j.bjoms.2016.05.030

Cited by 32 publications

(26 citation statements)

References 21 publications

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“…The mechanisms whereby ZOL modifies osteoprogenitors remain to be established and will be the subject of further research. Our data is in agreement with the growing body of evidence that ZOL modifies multiple cell types in vivo, including endothelial cells, immune cells, and hematopoietic stem cells (35,36,(48)(49)(50)(51)59), and is therefore not limited to osteoclast inhibition. Whether this is also the case in patients treated with ZOL is currently under investigation.…”

Section: Discussionsupporting

confidence: 92%

“…Osteogenic type-H vessels may therefore be more susceptible to inhibition by ZOL, potentially mediating the observed reduction in osteoprogenitors and osteoblasts. Consistent with previous findings (35,36,(48)(49)(50)(51), immunolabeling of femoral tissue sections revealed a significant reduction in the abundance of type-H vessels in mature compared with young mice (mature: 15.2% vs. young: 37.6%; P , 0.01; Fig. 6A).…”

Section: The Abundance Of Osteogenic Vascular Endothelium and The Expsupporting

confidence: 91%

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Bone marrow osteoprogenitors are depleted whereas osteoblasts are expanded independent of the osteogenic vasculature in response to zoledronic acid

Hughes¹,

Chen²,

Hunter³

et al. 2019

The FASEB Journal

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Zoledronic acid (ZOL) is an antiresorptive drug used to prevent bone loss in a variety of conditions, acting mainly through suppression of osteoclast activity. There is growing evidence that ZOL can also affect cells of the mesenchymal lineage in bone. We present novel data revealing significant changes in the abundance of perivascular mesenchymal stromal cells (MSCs)/osteoprogenitors and osteoblasts following the injection of ZOL, in vivo. In young mice with high bone turnover and an abundance of perivascular osteoprogenitors, ZOL significantly (P < 0.0001) increased new bone formation. This was accompanied by a decline in osterix‐positive osteoprogenitors and a corresponding increase in osteoblasts. However, these effects were not observed in mature mice with low bone turnover. Interestingly, the ZOL‐induced changes in cells of the mesenchymal lineage occurred independently of effects on the osteogenic vasculature. Thus, we demonstrate that a single, clinically relevant dose of ZOL can induce new bone formation in microenvironments enriched for perivascular MSC/osteoprogenitors and high osteogenic potential. This arises from the differentiation of perivascular osterix‐positive MSC/osteoprogenitors into osteoblasts at sites that are innately osteogenic. Collectively, our data demonstrate that ZOL affects multiple cell types in bone and has differential effects depending on the level of bone turnover.—Hughes, R., Chen, X., Hunter, K. D., Hobbs, J. K., Holen, I., Brown, N. J. Bone marrow osteoprogenitors are depleted whereas osteoblasts are expanded independent of the osteogenic vasculature in response to zoledronic acid. FASEB J. 33, 12768–12779 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 92%

Section: The Abundance Of Osteogenic Vascular Endothelium and The Expsupporting

confidence: 91%

Bone marrow osteoprogenitors are depleted whereas osteoblasts are expanded independent of the osteogenic vasculature in response to zoledronic acid

Hughes¹,

Chen²,

Hunter³

et al. 2019

The FASEB Journal

View full text Add to dashboard Cite

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“…HUVECs were analyzed in five studies. 108 , 112 , 113 , 122 , 123 In all studies, the effects of zoledronate, ibandronate, pamidronate, and clodronate were tested at concentrations of 5 to 500 μM. After BP application, HUVEC viability and migration decreased and apoptosis was induced.…”

Section: Resultsmentioning

confidence: 99%

Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials

et al. 2018

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ObjectiveThis study was performed to determine whether the results of prevailing in vivo and in vitro studies offer a reliable model for investigation of medication-related osteonecrosis of the jaw (MRONJ).MethodsEmbase, Medline, and the Cochrane Library were searched for articles published from September 2003 to June 2017 involving experimental approaches to the pathogenesis of MRONJ. In vivo and in vitro trials were analyzed with respect to the scientific question, study design, methodology, and results.ResultsOf 139 studies, 87, 46, and 6 conducted in vivo, in vitro, and both in vivo and in vitro experiments, respectively. Rats, mice, dogs, minipigs, sheep, and rabbits were the preferred animal models used. Osteoblasts, osteoclasts, fibroblasts, keratinocytes, macrophages, and human umbilical vein endothelial cells were the preferred cell types. Zoledronate, alendronate, ibandronate, and risedronate were the most frequent bisphosphonates used. MRONJ was most reliably induced in minipigs because of the close relationship with human bone physiology. In vitro studies showed that reduced viability, growth, and migration of cells in the bone and soft tissues were causative for MRONJ. Other than exposed jawbone after tooth extraction, no reliable cofactors were found.ConclusionThe minipig is the most suitable animal model for MRONJ.

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“…Nitrogen-containing bisphosphonates and statins inhibit the mevalonate pathway through interaction with farnesyl pyrophosphate synthase to prevent post-translational modification of proteins, resulting in decreased levels of inflammatory cytokines and matrix metalloproteinases [ 14 , 15 ]. Bisphosphonates also decrease a variety of mature vascular cells, which migrate into the vessel walls and injure vascular endothelial cells [ 16 , 17 ]. A clinical trial with elderly osteoporotic women, however, did not show an anti-atherosclerotic effect of ibandronate [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of combined treatment with bisphosphonate and vitamin D on atherosclerosis in patients with systemic lupus erythematosus: a propensity score-based analysis

et al. 2018

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BackgroundPremature atherosclerosis is one of the major complications of systemic lupus erythematosus (SLE). Recently, the biological linkage between atherosclerosis and osteoporosis has garnered much attention. The aim of this study is to explore correlation between the development of atherosclerosis and anti-osteoporotic treatment.MethodsConsecutive patients with SLE (n = 117) who underwent carotid ultrasonography were retrospectively analyzed using propensity scoring.ResultsOf the 117 patients, 42 (36%), 27 (23%), and 30 (26%) were receiving bisphosphonates and vitamin D (BP + VD), bisphosphonates alone, or vitamin D alone, respectively. Low bone mineral density was more frequent, and carotid plaque was less prevalent in the BP + VD group compared with other treatment groups. Age (OR = 1.57) and BP + VD treatment (OR = 0.24) were shown by multivariate analysis to be associated with the presence of carotid plaque. In all strata divided using the propensity score, carotid plaque was statistically significantly less prevalent (p = 0.015, Mantel-Haenszel test) in the BP + VD group relative to the other treatment groups.ConclusionCombined treatment with bisphosphonate and vitamin D may have a role in preventing atherosclerosis in patients with SLE.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1589-9) contains supplementary material, which is available to authorized users.

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Influence of zoledronic acid on proliferation, migration, and apoptosis of vascular endothelial cells

Cited by 32 publications

References 21 publications

Bone marrow osteoprogenitors are depleted whereas osteoblasts are expanded independent of the osteogenic vasculature in response to zoledronic acid

Bone marrow osteoprogenitors are depleted whereas osteoblasts are expanded independent of the osteogenic vasculature in response to zoledronic acid

Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study of in vivo and in vitro trials

Effect of combined treatment with bisphosphonate and vitamin D on atherosclerosis in patients with systemic lupus erythematosus: a propensity score-based analysis

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