A short treatment with an antibody to sclerostin can inhibit bone loss in an ongoing model of colitis.
Chronic inflammation leads to bone loss, and increased fracture rates have been reported in a number of human chronic inflammatory conditions. The study reported here investigates the skeletal effects of dosing a neutralizing antibody to the bone regulatory protein sclerostin in a mouse model of chronic colitis. When dosed prophylactically, an antibody to sclerostin (Scl-AbI) did not reduce the weight loss or histological changes associated with colitis but did prevent inflammation-induced bone loss. At the end of the experiment, Scl-AbI-treated animals had a significantly higher femoral BMD (+27%, p < 0.05) than control antibody (Cntrl-Ab)-treated animals. In a second experiment, treatment with Scl-AbI was delayed until colitis had developed, by which time the mechanical properties of femurs in colitic animals were significantly worse than those of healthy age-matched control mice (maximum load, -26%, p < 0.05; energy, -37%, p < 0.05; ultimate strength, -33%, p < 0.05; elastic modulus, -17%, p < 0.05). A short treatment with Scl-AbI halted bone loss and reversed the decline of both intrinsic and extrinsic mechanical properties of the femur such that, after 19 days of treatment, the bone mechanical properties in the Scl-AbI-treated animals were not significantly different from those of noncolitic age-matched controls. Serum markers of bone formation and resorption suggested that the antibody to sclerostin stimulated osteoblast activity and inhibited osteoclast-mediated bone resorption.
Department of Inflammation Biology, UCB Celltech, Slough, United Kingdom.
Alison
A
Eddleston
Massimo
M
Marenzana
Adrian R
AR
Moore
Paul
P
Stephens
Mariusz
M
Muzylak
Diane
D
Marshall
Martyn K
MK
Robinson
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D001862:Bone Resorption / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D003092:Colitis / Q000097:blood / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers / Q000276:immunology*; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D055114:X-Ray Microtomography
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C486030:Sost protein, mouse