Evidence map›Paper›PMID 41354629›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Rescuing Mitochondrial Dysfunction in Macrophages Prevents Osteonecrosis of the Jaw in Anti-Resorptive Therapy.

Hang Zhang, Xin Shen, Haiyang Liu, Xinxi Yuan, Mumin Cao, Xuepeng Lv, Ziji Ling, Songsong Guo, Rongyao Xu, Xiang Li and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

11 authors.

Hang ZhangState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.ORCID https://orcid.org/0000-0002-5187-8732
Xin ShenState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Haiyang LiuState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Xinxi YuanState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Mumin CaoDepartment of Orthopaedics, Orthopaedic Trauma Institute (OTI), Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Xuepeng LvState Key Lab of Digital Medical Engineering, Jiangsu Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 211189, China.
Ziji LingState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Songsong GuoState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Rongyao XuState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Xiang LiState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Hongbing JiangState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.ORCID https://orcid.org/0000-0002-3748-0381

Funding

Education-Jiangsu Provincial Research Hospital Cultivation Unit YJXYYJSDW4Jiangsu Provincial Medical Innovation Center CXZX202227National Natural Science Foundation of China 81771092National Natural Science Foundation of China 81970910
6 · The paper itself

Abstract

Mitochondria-driven macrophage dysregulation contributes significantly to inflammatory disease progression; however, the mechanism underlying bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains unclear. This study demonstrates that zoledronic acid (ZA) disrupts mitochondrial bioenergetic function in macrophages, leading to elevated mitochondrial membrane potential, excessive mitochondrial reactive oxygen species (mtROS), and increased HIF-1α expression, which together promote a pro-inflammatory transition in macrophages. ZA further inhibits autophagy by activating the TLR4-MyD88/PI3K-AKT-mTOR pathway, preventing the clearance of dysfunctional mitochondria and sustaining superoxide production. Genetic loss of Atg5 in innate immune cells disrupts autophagosome maturation and markedly worsens ZA-induced BRONJ development. To restore mitochondrial degradation and biofunction, ZA-loaded nanoparticles incorporating the mTOR inhibitor rapamycin (ZDPR) are developed. ZDPR effectively prevents BRONJ and exerts therapeutic benefits in osteoporosis and osteolysis. These findings highlight bone-targeted mitochondria rescue as a promising strategy to enhance antiresorptive therapy.

Indexed as

Bisphosphonate-Associated Osteonecrosis of the JawBone Density Conservation AgentsMacrophagesMitochondriaZoledronic AcidAnimalsAutophagyMaleMiceMice, Inbred C57BLReactive Oxygen SpeciesBone Density Conservation AgentsReactive Oxygen SpeciesZoledronic Acidanti‐resorptive therapyautophagybisphosphonate‐related osteonecrosis of the jawmacrophage polarizationmitochondrial dysfunctionPI3K‐AKT‐mTOR pathwayzoledronic acid

Identifiers

PMID41354629
PMCPMC12931161

What OpenQuestion holds

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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.