Evidence map›Paper›PMID 24291703›Full record

ArticleThe spine journal : official journal of the North American Spine Society2014

Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease.

Khoi D Than, Shayan U Rahman, Lin Wang, Adam Khan, Kwaku A Kyere, Tracey T Than, Yoshinari Miyata, Yoon-Shin Park, Frank La Marca, Hyungjin M Kim and 3 more

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In one paragraph

Article in The spine journal : official journal of the North American Spine Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

33 citing papers in PubMed, 56 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

13 authors at 1 institution in 1 country.

Khoi D ThanDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Shayan U RahmanDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Lin WangDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Adam KhanUniversity of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Kwaku A KyereUniversity of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Tracey T ThanDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Yoshinari MiyataDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Yoon-Shin ParkDepartment of Pharmaceutical Sciences, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Frank La MarcaDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Hyungjin M KimDepartment of Biostatistics, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Huina ZhangDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Paul ParkDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Chia-Ying LinDepartment of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA. Electronic address: lincy@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Simvastatin to Retard Degenerative Disc DiseaseR01AR056649 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIN, CHIA-YING JAMES · 2010 to 2013
$1.3M
NIAMS NIH HHS R01 AR056649
6 · The paper itself

Abstract

background contextA large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein 2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to upregulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE: The purpose of the present study was to develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/

settingThe setting of this study is the laboratory investigation.

methodsDisc injury was induced in 272 rats via 21-ga needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the magnetic resonance imaging (MRI) index (number of pixels multiplied by the corresponding image densities) was determined. Histologically, disc spaces were read by three blinded scorers using a previously described histologic grading scale. Genetically, nuclei pulposi were harvested, and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression.

resultsRadiologically, discs treated with 5 mg/mL of simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks after treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated improved grades compared with discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control.

conclusionsDegenerate discs treated with 5 mg/mL of simvastatin in a hydrogel carrier demonstrated radiographic and histologic features resembling normal noninjured IVDs. In addition, the gene expression of aggrecan and collagen type II (important constituents of the IVD extracellular matrix) was upregulated in treated discs. Injection of simvastatin into degenerate IVDs may result in retardation of disc degeneration and represents a promising investigational therapy for conservative treatment of DDD.

Indexed as

AnimalsBone Morphogenetic Protein 2Disease Models, AnimalExtracellular MatrixGene ExpressionHydroxymethylglutaryl-CoA Reductase InhibitorsInjections, SpinalIntervertebral DiscIntervertebral Disc DegenerationMagnetic Resonance ImagingMaleRatsRats, Sprague-DawleyRegenerationSimvastatinUp-RegulationBone Morphogenetic Protein 2Hydroxymethylglutaryl-CoA Reductase InhibitorsSimvastatinBack painBMP-2Degenerative disc diseaseDiscogenic back painRodent modelSimvastatin

Identifiers

PMID24291703
PMCPMC4032598
OpenAlexW2017410059

What OpenQuestion holds

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LicenceTDM
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.