Evidence map›Paper›PMID 30032440›Full record

ArticleJournal of bone and mineral metabolism2019

Metformin protects bone mass in ultra-high-molecular-weight polyethylene particle-induced osteolysis by regulating osteocyte secretion.

Zhao Yan, Shu Zhu, Xiaoxi Tian, Zichen Ye, Dongsheng Zhai, Zheng Zhu, Di Wei, Qingsheng Zhu, Zifan Lu, Xiaorui Cao

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of bone and mineral metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 47% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Metformin and bone metabolism: unraveling their direct and indirect effects.Therapeutic advances in endocrinology and metabolism · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. Review
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

10 authors at 2 institutions in 1 country.

Zhao YanDepartment of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Shu ZhuDepartment of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Xiaoxi TianEmergency Department of Tangdu Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Zichen YeState Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Dongsheng ZhaiState Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Zheng ZhuDepartment of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Di WeiDepartment of Urinary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Qingsheng ZhuDepartment of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
Zifan LuState Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. luzfliuq@fmmu.edu.cn.
Xiaorui CaoDepartment of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. caoxr@fmmu.edu.cn.
Air Force Medical University · CNXijing Hospital · CN

Funding

Project of Natural Science Foundation of the National Natural Science Foundation of China 81501936
6 · The paper itself

Abstract

Metformin, an anti-hyperglycemic agent used for type 2 diabetes, has recently been found to have more effects apart from glucose regulation. We found that, in ultra-high-molecular-weight polyethylene particle-induced osteolysis mouse models, metformin had bone protect property and reduced the negative regulator of bone formation sclerostin (SOST) and Dickkopf-related protein 1 (DKK1), and increased osteoprotegerin (OPG) secretion and the ratio of OPG/Receptor Activator for Nuclear Factor-κB Ligand (RANKL). In vitro, we established a 3D co-culture system in which metformin affects osteoblasts and osteoclasts through mature osteocytes secretion. Metformin (50 μM) significantly decreased SOST and DKK1 mRNA expression, stimulating alkaline phosphatase activity and proliferation of osteoblast, and increased OPG secretion and the ratio of OPG/RANKL, inhibiting osteoclastogenesis. Moreover, the effect on OPG was reversed by adenosine 5'-monophosphate-activated protein kinase inhibitor, Compound C. Our finding suggests that metformin induces differentiation and mineralization of osteoblasts, while inhibits osteoclastogenesis via mature osteocytes secretion. Therefore, the drug might be beneficial for not only diabetes but also in other bone disorders by acting on mature osteocytes.

Indexed as

Adaptor Proteins, Signal TransducingAdenylate KinaseAnimalsBone and BonesCell DifferentiationCell ProliferationCells, CulturedCoculture TechniquesDisease Models, AnimalGlycoproteinsInflammationIntercellular Signaling Peptides and ProteinsMaleMetforminMice, Inbred C57BLModels, BiologicalAdaptor Proteins, Signal TransducingAdenylate KinaseDkk1 protein, mouseGlycoproteinsIntercellular Signaling Peptides and ProteinsMetforminOsteoprotegerinPolyethylenesProtective AgentsRANK LigandSost protein, mouseultra-high molecular weight polyethyleneDKK1MetforminOPGOsteocyteSclerostin

Identifiers

PMID30032440
OpenAlexW2884459032

What OpenQuestion holds

Textmetadata
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.