Evidence map›Paper›PMID 33637048›Full record

Trial reportMolecular medicine (Cambridge, Mass.)2021

Administration of zoledronic acid alleviates osteoporosis in HIV patients by suppressing osteoclastogenesis via regulating RANKL expression.

Wei Lin, Xing-Fu Li, Dong-Cheng Ren, Meng Song, Li Duan, Jin-Zhu Liu, Zi-Rui Zhan

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Molecular medicine (Cambridge, Mass.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Wei LinDepartment of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China.
Xing-Fu LiDepartment of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China.
Dong-Cheng RenDepartment of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China.
Meng SongDepartment of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China.
Li DuanDepartment of Orthopedics, Shenzhen No. 2 People's Hospital, Shenzhen, 518000, People's Republic of China.
Jin-Zhu LiuDepartment of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China.
Zi-Rui ZhanDepartment of Orthopedics, Third People's Hospital of Shenzhen, No. 29 Bulan Road, Longgang, Shenzhen, 518112, Guangdong, People's Republic of China. orthomedical@126.com.ORCID 0000-0002-0537-0794
Shenzhen Third People’s Hospital · CNLonggang Central Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOsteoporosis is a common phenomenon in HIV patients on tenofovir treatment, but its underlying mechanisms remain to be explored.

methodsQuantitative real-time PCR was performed to analyze the expression of miR-302, miR-101, miR-145 and osteoclast-specific genes in the serum of HIV patients treated with tenofovir and ZOL. ELISA was used to evaluate the expression of RANKL, SMAD3 and PRKACB in the serum of these patients. Luciferase assay was carried out to explore the inhibitory effects of miR-302, miR-101 and miR-145 on the expression of PRKACB, RANKL and SMAD3, respectively. Western blot was used to examine the expression of genes involved in NF‑κB and JNK signaling pathways.

resultsZOL treatment significantly suppressed the expression of CTx and osteocalcin in HIV patients treated with tenofovir. The BMD loss of HIV patients treated with tenofovir was effectively hindered by ZOL treatment. Mechanistically, the expression of miR-302, miR-101, miR-145, RANKL, SMAD3 and PRKACB in the serum was remarkably activated by ZOL treatment. Luciferase assays showed that miR-302, miR-101 and miR-145 effectively suppressed the expression of PRKACB, RANKL and SMAD3, respectively, through binding to their 3' UTR. Furthermore, ZOL treatment notably restored the normal expression of osteoclast‑specific genes while activating NF‑κB and JNK signaling pathways.

conclusionThe findings of this study demonstrated that administration of ZOL suppressed the expression of RANKL via modulating signaling pathways of miR-101-3p/RANKL, miR-302/PRKACB/RANKL and miR-145/SMAD3/RANKL. Furthermore, down-regulated expression of RANKL by ZOL treatment alleviated osteoporosis in HIV-positive subjects treated with tenofovir.

Indexed as

AdultAnti-Retroviral AgentsBone DensityBone Density Conservation AgentsCell ProliferationCells, CulturedCyclic AMP-Dependent Protein Kinase Catalytic SubunitsFemaleHIV InfectionsHumansMaleMAP Kinase Signaling SystemMicroRNAsMiddle AgedOsteoclastsOsteogenesisAnti-Retroviral AgentsBone Density Conservation AgentsCyclic AMP-Dependent Protein Kinase Catalytic SubunitsMicroRNAsPRKACB protein, humanRANK LigandSmad3 ProteinSMAD3 protein, humanTenofovirTNFSF11 protein, humanZoledronic AcidHIVmiRNAOsteoclastogenesisOsteoporosisRANKLZoledronic acid

Identifiers

PMID33637048
PMCPMC7908730
OpenAlexW3130701107

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.