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Bone. 2016 Mar;84:222-229. doi: 10.1016/j.bone.2016.01.001. Epub 2016 Jan 6.

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

Author information

1
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan Ann Arbor, MI, USA.
2
Department of Chemistry, University of Michigan Ann Arbor, MI, USA.
3
Bone and Extracellular Matrix Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA.
4
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan Ann Arbor, MI, USA.
5
Orthopaedic 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.

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.

KEYWORDS:

Anabolic therapy; Bone quality; Nanoindentation; Osteogenesis imperfecta; Raman spectroscopy; Sclerostin antibody

PMID:
26769006
PMCID:
PMC4757447
[Available on 2017-03-01]
DOI:
10.1016/j.bone.2016.01.001
[Indexed for MEDLINE]
Free PMC Article

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