Sclerostin antibody treatment enhances bone strength but does not prevent growth retardation in young mice treated with dexamethasone.

Abstract

OBJECTIVE:

Exposure to supraphysiologic levels of glucocorticoid drugs is known to have detrimental effects on bone formation and linear growth. Patients with sclerosteosis lack the bone regulatory protein sclerostin, have excessive bone formation, and are typically above average in height. This study was undertaken to characterize the effects of a monoclonal antibody to sclerostin (Scl-AbI) in mice exposed to dexamethasone (DEX).

METHODS:

Young mice were concomitantly treated with DEX (or vehicle control) and Scl-AbI antibody (or isotype-matched control antibody [Ctrl-Ab]) in 2 independent studies. Linear growth, the volume and strength of the bones, and the levels of bone turnover markers were analyzed.

RESULTS:

In DEX-treated mice, Scl-AbI had no significant effect on linear growth when compared to control treatment (Ctrl-Ab). However, in mice treated with DEX and Scl-ABI, a significant increase in trabecular bone at the femoral metaphysis (bone volume/total volume +117% versus Ctrl-Ab-treated mice) and in the width and volume of the cortical bone at the femoral diaphysis (+24% and +20%, respectively, versus Ctrl-Ab-treated mice) was noted. Scl-AbI treatment also improved mechanical strength (as assessed by 4-point bending studies) at the femoral diaphysis in DEX-treated mice (maximum load +60% and ultimate strength +47% in Scl-AbI-treated mice versus Ctrl-Ab-treated mice). Elevated osteocalcin levels were not detected in DEX-treated mice that received Scl-AbI, although levels of type 5b tartrate-resistant acid phosphatase were significantly lower than those observed in mice receiving DEX and Ctrl-Ab.

CONCLUSION:

Scl-AbI treatment does not prevent the detrimental effects of DEX on linear growth, but the antibody does increase both cortical and trabecular bone and improves bone mechanical properties in DEX-treated mice.

• Authors: M Marenzana, K Greenslade, A Eddleston, R Okoye, D Marshall, A Moore, M K Robinson
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 63 Issue 8 Pg. 2385-95 (Aug 2011) ISSN: 1529-0131 [Electronic] United States
• PMID: 21484764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 by the American College of Rheumatology.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antibodies, Monoclonal
• Glucocorticoids
• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Sost protein, mouse
• Dexamethasone

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Bone Density (drug effects)
• Dexamethasone (pharmacology)
• Femur (drug effects, immunology)
• Glucocorticoids (pharmacology)
• Glycoproteins (immunology)
• Growth (drug effects, immunology)
• Intercellular Signaling Peptides and Proteins
• Mice
• Osteogenesis (drug effects)