Tissue level material composition and mechanical properties in Brtl/+ mouse model of Osteogenesis Imperfecta after sclerostin antibody treatment
2015
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 v 1 , carbonate v 1 , 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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