Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment

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

doi:10.1117/12.2080261

26 February 2015 Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment

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

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Proceedings Volume 9303, Photonic Therapeutics and Diagnostics XI; 93033U (2015) https://doi.org/10.1117/12.2080261
Event: SPIE BiOS, 2015, San Francisco, California, United States

Abstract

Osteogenesis imperfecta (OI) is a genetic disorder resulting in defective collagen or collagen-associated proteins and fragile, brittle bones. To date, therapies to improve OI bone mass, such as bisphosphonates, have increased bone mass in the axial skeleton of OI patients, but have shown limited effects at reducing long bone fragility. Sclerostin antibody (Scl- Ab), currently in clinical trials for osteoporosis, stimulates bone formation and may have the potential to reduce long bone fracture rates in OI patients. Scl-Ab has been investigated as an anabolic therapy for OI in the Brtl/+ mouse model of moderately severe Type IV OI. While Scl-Ab increases long bone mass in the Brtl/+ mouse, it is not known whether material properties and composition changes also occur. Here, we report on the effects of Scl-Ab on wild type and Brtl/+ young (3 week) and adult (6 month) male mice. Scl-Ab was administered over 5 weeks (25mg/kg, 2x/week). Raman microspectroscopy and nanoindentation are used for bone composition and biomechanical bone property measurements in excised bone. Fluorescent labels (calcein and alizarin) at 4 time points over the entire treatment period are used to enable measurements at specific tissue age. Differences between wild type and Brtl/+ groups included variations in the mineral and matrix lattices, particularly the phosphate v₁, carbonate v₁, and the v(CC) proline and hydroxyproline stretch vibrations. Results of Raman spectroscopy corresponded to nanoindentation findings which indicated that old bone (near midcortex) is stiffer (higher elastic modulus) than new bone. We compare and contrast mineral to matrix and carbonate to phosphate ratios in young and adult mice with and without treatment.

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William R. Lloyd III, Benjamin P. Sinder, Joseph Salemi, Michael S. Ominsky, Joan C. Marini, Michelle S. Caird, Michael D. Morris, and Kenneth M. Kozloff "Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment", Proc. SPIE 9303, Photonic Therapeutics and Diagnostics XI, 93033U (26 February 2015); https://doi.org/10.1117/12.2080261

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KEYWORDS

Bone

Tissues

Raman spectroscopy

Minerals

Carbonates

Mouse models

Fluorescent markers

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