Evidence map›Paper›PMID 39062176›Full record

ArticleBiomedicines2024

Anti-Microbial Drug Metronidazole Promotes Fracture Healing: Enhancement in the Bone Regenerative Efficacy of the Drug by a Biodegradable Sustained-Release In Situ Gel Formulation.

Shivali Duggal, Shivani Sharma, Nikhil Rai, Divya Chauhan, Vishal Upadhyay, Swati Srivastava, Konica Porwal, Chirag Kulkarni, Arun K Trivedi, Jiaur R Gayen and 3 more

Abstract read
In one paragraph

Article in Biomedicines, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

13 authors.

Shivali DuggalDivision of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.
Shivani SharmaDivision of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.
Nikhil RaiAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Divya ChauhanAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Vishal UpadhyayAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Swati SrivastavaDivision of Cancer Biology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.
Konica PorwalDivision of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.ORCID 0000-0002-6447-4681
Chirag KulkarniDivision of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.
Arun K TrivediAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.ORCID 0000-0002-6316-0947
Jiaur R GayenDivision of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.ORCID 0000-0001-7703-9307
Prabhat R MishraDivision of Pharmaceutics and Pharmacokinetics, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.
Naibedya ChattopadhyayDivision of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.ORCID 0000-0003-2473-0246
Subhashis PalDivision of Endocrinology, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, India.ORCID 0000-0002-3916-5545

Funding

Council of Scientific and Industrial Research MLP 2035
6 · The paper itself

Abstract

Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures.

Indexed as

anti-microbial drugfracture healingin situ gel formulationosteoblast differentiationosteogenic

Identifiers

PMID39062176
PMCPMC11274654

What Socratic 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 Socratic graph.