Evidence map›Paper›PMID 26769006›Full record

ArticleBone2016

Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

Benjamin P Sinder, William R Lloyd, Joseph D Salemi, Joan C Marini, Michelle S Caird, Michael D Morris, Kenneth M Kozloff

Abstract read
In one paragraph

Article in Bone, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
7.8field-weighted citation impact, top 3% 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

27 citing papers in PubMed, 41 citations in OpenAlex.

  1. Osteogenesis imperfecta: pathogenesis, classification, and treatment.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025
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  15. New perspectives on the treatment of skeletal dysplasia.Therapeutic advances in endocrinology and metabolism · 2020
    Review
  16. Article
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  19. Low Dose of Bisphosphonate Enhances Sclerostin Antibody-Induced Trabecular Bone Mass Gains in Brtl/+ Osteogenesis Imperfecta Mouse Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2018
    Article
  20. PTH(1-34) and zoledronic acid have differing longitudinal effects on juvenile mouse femur strength and morphology.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2017
    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

7 authors at 2 institutions in 1 country.

Benjamin P SinderOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan Ann Arbor, MI, USA.
William R LloydDepartment of Chemistry, University of Michigan Ann Arbor, MI, USA.
Joseph D SalemiOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan Ann Arbor, MI, USA.
Joan C MariniBone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
Michelle S CairdOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA.
Michael D MorrisDepartment of Chemistry, University of Michigan Ann Arbor, MI, USA.
Kenneth M KozloffOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan Ann Arbor, MI, USA. Electronic address: kenkoz@umich.edu.
University of Michigan–Ann Arbor · USEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Dynamic Spectroscopic Imaging in Bone BiomechanicsR01AR052010 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORRIS, MICHAEL DAVID · 2005 to 2015
$3.7M
Sclerostin Antibody Therapy for Treatment of Osteogenesis ImperfectaR01AR062522 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOZLOFF, KENNETH M · 2012 to 2016
$1.8M
NIAMS NIH HHS R01 AR052010NIAMS NIH HHS R01 AR062522
6 · The paper itself

Abstract

Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and animal age on bone quality.

Indexed as

Adaptor Proteins, Signal TransducingAgingAnimalsAntibodiesBone and BonesBone MatrixElastic ModulusFemaleFemurGenotypeGlycoproteinsIntercellular Signaling Peptides and ProteinsMice, Inbred C57BLMineralsOsteogenesis ImperfectaAdaptor Proteins, Signal TransducingAntibodiesGlycoproteinsIntercellular Signaling Peptides and ProteinsMineralsSost protein, mouseAnabolic therapyBone qualityNanoindentationOsteogenesis imperfectaRaman spectroscopySclerostin antibody

Identifiers

PMID26769006
PMCPMC4757447
OpenAlexW2230469740

What OpenQuestion holds

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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.