Evidence map›Paper›PMID 34036438›Full record

ArticleOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2021

Bone biomechanical properties and tissue-scale bone quality in a genetic mouse model of familial dysautonomia.

G Vahidi, H Flook, V Sherk, M Mergy, F Lefcort, C M Heveran

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-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

4 citing papers in PubMed, 6 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

6 authors at 2 institutions in 1 country.

G VahidiDepartment of Mechanical & Industrial Engineerings, Montana State University, Bozeman, MT, USA.
H FlookDepartment of Mechanical & Industrial Engineerings, Montana State University, Bozeman, MT, USA.
V SherkDepartment of Orthopaedics, University of Colorado School of Medicine, Aurora, CO, USA.
M MergyDepartment of Microbiology & Immunology, Montana State University, Bozeman, MT, USA.
F LefcortDepartment of Microbiology & Immunology, Montana State University, Bozeman, MT, USA.
C M HeveranDepartment of Mechanical & Industrial Engineerings, Montana State University, Bozeman, MT, USA. chelsea.heveran@montana.edu.ORCID http://orcid.org/0000-0002-1406-7439
Montana State University · USUniversity of Colorado Denver · US

Funding

Research Core (Developmental Research Project Program)P20GM103474 · NIGMS · MONTANA STATE UNIVERSITY - BOZEMAN · PI Jeffrey Good · 2012 to 2026
$60.0M
Metabolic Control of gut-brain axis in Familial dysautonomia Supplement to parent grant 1R01DK117473-01A1 to support a PhD candidate/graduate student from an under-represented minorityR01DK117473 · NIDDK · MONTANA STATE UNIVERSITY - BOZEMAN · PI COPIE, VALERIE, WALK, SETH T · 2018 to 2022
$3.0M
WHY DO MUTATIONS IN IKBKAP CAUSE FAMILIAL DYSAUTONOMIA?R01NS086796 · NINDS · MONTANA STATE UNIVERSITY - BOZEMAN · PI LEFCORT, FRANCES · 2014 to 2018
$1.6M
NIDDK NIH HHS DK117473NIDDK NIH HHS R01 DK117473NIGMS NIH HHS P20 GM103474NIGMS NIH HHS P20GM103474NINDS NIH HHS NS086796NINDS NIH HHS R01 NS086796
6 · The paper itself

Abstract

purposeFamilial dysautonomia (FD) is associated with a high prevalence of bone fractures, but the impacts of the disease on bone mass and quality are unclear. The purpose of this study was to evaluate tissue through whole-bone scale bone quality in a mouse model of FD.

methodsFemurs from mature adult Tuba1a-Cre; Elp1

resultsConsistent with prior studies on this mouse model, the Elp1 CKO mouse model recapitulated several key hallmarks of human FD, with one difference being the male mice tended to have a more severe phenotype than females. Deletion of Elp1 in neurons (using the neuronal-specific Tuba1a-cre) led to a significantly reduced whole-bone toughness but not strength or modulus. Elp1 CKO female mice had reduced trabecular microarchitecture (BV/TV, Tb.Th, Conn.D.) but not cortical geometry. The mutant mice also had a small but significant reduction in cortical bone nanoindentation modulus. While bone tissue mineralization and mineral maturity were not impaired, FD mice may have altered collagen secondary structure. Changes in collagen secondary structure were inversely correlated with bone toughness. BMD from dual-energy x-ray absorptiometry (DXA) was unchanged with FD.

conclusionThe deletion of Elp1 in neurons is sufficient to generate a mouse line which demonstrates loss of whole-bone toughness, consistent with the poor bone quality suspected in the clinical setting. The Elp1 CKO model, as with human FD, impacts the nervous system, gut, kidney function, mobility, gait, and posture. The bone quality phenotype of Elp1 CKO mice, which includes altered microarchitecture and tissue-scale material properties, is complex and likely influenced by these multisystemic changes. This mouse model may provide a useful platform to not only investigate the mechanisms responsible for bone fragility in FD, but also a powerful model system with which to evaluate potential therapeutic interventions for bone fragility in FD patients.

Indexed as

Dysautonomia, FamilialAbsorptiometry, PhotonAnimalsBone and BonesBone DensityDisease Models, AnimalFemaleHumansIntracellular Signaling Peptides and ProteinsMaleMiceMice, KnockoutIkbkap protein, mouseIntracellular Signaling Peptides and ProteinsBone qualityBone toughnessFamilial dysautonomia

Identifiers

PMID34036438
PMCPMC8563419
OpenAlexW3164167330

What OpenQuestion holds

Textmetadata
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.