Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta

• Published in: Bone (New York, N.Y.) N.Y.), 2014-09, Vol.66, p.182-188
• Main Authors: Roschger, Andreas, Roschger, Paul, Keplingter, Petra, Klaushofer, Klaus, Abdullah, Sami, Kneissel, Michaela, Rauch, Frank
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - pharmacology; Antibodies - therapeutic use; Biological and medical sciences; Biomechanical Phenomena - drug effects; Body Weight - drug effects; Bone formation; Disease Models, Animal; Diseases of the osteoarticular system; Femur - diagnostic imaging; Femur - drug effects; Femur - pathology; Femur - physiopathology; Fundamental and applied biological sciences. Psychology; Glycoproteins - immunology; Lumbar Vertebrae - diagnostic imaging; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - pathology; Lumbar Vertebrae - physiopathology; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Mice; Orthopedics; Osteogenesis imperfecta; Osteogenesis Imperfecta - blood; Osteogenesis Imperfecta - drug therapy; Osteogenesis Imperfecta - pathology; Osteogenesis Imperfecta - physiopathology; Quantitative backscattered electron imaging; Sclerostin; Vertebrates: anatomy and physiology, studies on body, several organs or systems; X-Ray Microtomography
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2014.06.015

Abstract Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4 weeks in male Col1a1Jrt /+ mice, a model of severe dominant OI, starting either at 4 weeks (growing mice) or at 20 weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1Jrt /+ mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model.