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Osteoporosis International

Erschienen in:

01.08.2014 | Original Article

Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength

verfasst von: B. P. Sinder, L. E. White, J. D. Salemi, M. S. Ominsky, M. S. Caird, J. C. Marini, K. M. Kozloff

Erschienen in: Osteoporosis International | Ausgabe 8/2014

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Abstract

Summary

Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect.

Introduction

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1.

Methods

Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed.

Results

Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength.

Conclusion

Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

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Titel: Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength
verfasst von: B. P. Sinder
L. E. White
J. D. Salemi
M. S. Ominsky
M. S. Caird
J. C. Marini
K. M. Kozloff
Publikationsdatum: 01.08.2014
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 8/2014
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2737-y

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Springer Medizin

Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength

Abstract

Summary

Introduction

Methods

Results

Conclusion

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Springer Medizin

Abstract

Summary

Introduction

Methods

Results

Conclusion

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