Low concentrations of zoledronic acid are better at regulating bone formation and repair

Yang, Xiaomeng; Li, Yanqin; Li, Zhiliang; Wang, Yanzhou; Zhao, Fei; Han, Jinxiang

doi:10.5582/irdr.2013.v2.1.18

Cited by 6 publications

(3 citation statements)

References 34 publications

(28 reference statements)

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“…For example, ZOL inhibited the function of osteoblasts in a dose-dependent manner in vitro. [63][64][65] Moreover, ZOL also induced apoptosis of osteoblasts. 66 We also showed that the TNF-α level in the BM was upregulated in the ZOL+TDF group compared with that in the LGG+TDF group.…”

Section: Discussionmentioning

confidence: 92%

Lactobacillus rhamnosusGG attenuates tenofovir disoproxil fumarate-induced bone loss in male miceviagut-microbiota-dependent anti-inflammation

Líu

et al. 2019

Therapeutic Advances in Chronic Disease

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Background: Although antiretroviral agents trigger bone loss in human immunodeficiency virus patients, tenofovir disoproxil fumarate (TDF) induces more severe bone damage, such as osteoporosis. While, the mechanisms are unclear, probiotic supplements may be effective against osteoporosis. Methods: C57BL6/J mice were administered with Lactobacillus rhamnosus GG (LGG)+TDF, TDF, and zoledronic acid+TDF, respectively. Bone morphometry and biomechanics were evaluated using microcomputed tomography, bone slicing, and flexural tests. The lymphocyte, proinflammatory cytokines, and intestinal permeability levels were detected using enzyme-linked immunosorbent assays, quantitative real-time polymerase chain reaction, and flow cytometry. The gut microbiota composition and metabolomics were analyzed using 16S recombinant deoxyribonucleic acid pyrosequencing and ultra-performance liquid-chromatography–quadrupole time-of-flight mass spectrometry. Results: LGG administered orally induced marked increases in trabecular bone microarchitecture, cortical bone volume, and biomechanical properties in the LGG+TDF group compared with that in the TDF-only group. Moreover, LGG treatment increased intestinal barrier integrity, expanded regulatory T cells, decreased Th17 cells, and downregulated osteoclastogenesis-related cytokines in the bone marrow, spleen, and gut. Furthermore, LGG reconstructed the gut microbiota and changed the metabolite composition, especially lysophosphatidylcholine levels. However, the amount of N-acetyl-leukotriene E4 was the highest in the TDF-only group. Conclusion: LGG reconstructed the community structure of the gut microbiota, promoted the expression of lysophosphatidylcholines, and improved intestinal integrity to suppress the TDF-induced inflammatory response, which resulted in attenuation of TDF-induced bone loss in mice. LGG probiotics may be a safe and effective strategy to prevent and treat TDF-induced osteoporosis.

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Section: Discussionmentioning

confidence: 92%

Lactobacillus rhamnosusGG attenuates tenofovir disoproxil fumarate-induced bone loss in male miceviagut-microbiota-dependent anti-inflammation

Líu

et al. 2019

Therapeutic Advances in Chronic Disease

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“…The 800 μg/ml concentration promoted significantly increased bone volume and bone density compared with the lower dosage group, without significant differences noted in bone‐implant contact. An in vitro study assessed cell proliferation, differentiation and mineralization following application of zoledronic acid ranging from 10 −3 M to 10 −13 M. Zoledronic acid mediated cell proliferation in a dose‐dependent manner, while having greater effect on cell differentiation and mineralization at concentrations below 10 −8 M (Yang et al., ). Future studies appear required to quantify zoledronic acid dosage optimized to promote implant‐bone anchorage without side effects.…”

Section: Discussionmentioning

confidence: 99%

Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model

Kwon

Lee

Wikesjö

et al. 2017

J Clinic Periodontology

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“…Such negative effect of ZA toward osteoblasts proliferation and functions was also detectable at much lower concentrations (e.g. above 10 −8 mol/L) [ 14 ]. Based on such updates, providing an effective and safe protocol for long-term ZA treatment for osteoporosis remains a challenge.…”

Section: Introductionmentioning

confidence: 99%

Prior administration of vitamin K2 improves the therapeutic effects of zoledronic acid in ovariectomized rats by antagonizing zoledronic acid-induced inhibition of osteoblasts proliferation and mineralization

Zhao

et al. 2018

PLoS ONE

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Zoledronic acid (ZA) exerts complex influence on bone by suppressing bone resorption, mostly due to the direct osteoclasts inhibition and uncertain influence on osteoblasts. Vitamin K2 (VK2, Menaquinone-4) as an anabolic agent stimulates bone formation via anti-apoptosis in osteoblasts and mild osteoclasts inhibition. Based on these knowledge, the therapeutic effect of the combined or sequential therapy of VK2 and ZA depends on the influence on the osteoblasts, since both cases exert similar inhibitory effect on osteoclasts. In a series of in vitro studies, we confirmed the protective effect of VK2 in osteoblasts culture, especially when followed by exposure to ZA, and the proliferation and mineralization inhibition induced by ZA towards osteoblasts. For mechanism study, expression of bcl-2/bax, Runx2 and Sost in cells were examined. For in vivo studies, an osteoporosis animal model was established in rats via ovariectomy (OVX) and subjected to sequential treatment, namely VK2 followed by ZA. Bone mineral density (BMD) was measured by Dual energy X-ray absorptionmetry (DEXA), morphology and mechanical parameters by micro-computed tomography (micro-CT), mechanical strength by an electro-hydraulic fatigue-testing machine. The bone calcium, hydroxyproline content, blood lipids were evaluated using microplate technique, and the bone surface turnover was evaluated using the fluorescence in corporation method. It was found that VK2 pretreatment partially prevented the inhibition of bone formation caused by ZA, which was reflected by indices like BMD, bone calcium content and bone strength. The underling mechanisms for protection of VK2 pretreatment, mainly demonstrated via in vitro studies, included inhibiting apoptosis and depressing Sost expression in osteoblasts, which in turn improved the osteoporosis therapeutic effects of ZA. These findings suggested that pretreatment with VK2 before ZA therapy might serve a new long-term therapy protocol for osteoporosis.

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Low concentrations of zoledronic acid are better at regulating bone formation and repair

Abstract: SummaryThe purpose of this study was to investigate optimal concentrations of zoledronic acid (ZA) in terms of their effect on the proliferation, differentiation, and mineralization of primary osteoblasts (

Cited by 6 publications

References 34 publications

Lactobacillus rhamnosusGG attenuates tenofovir disoproxil fumarate-induced bone loss in male miceviagut-microbiota-dependent anti-inflammation

Lactobacillus rhamnosusGG attenuates tenofovir disoproxil fumarate-induced bone loss in male miceviagut-microbiota-dependent anti-inflammation

Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model

Prior administration of vitamin K2 improves the therapeutic effects of zoledronic acid in ovariectomized rats by antagonizing zoledronic acid-induced inhibition of osteoblasts proliferation and mineralization

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