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Research Article

Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats

, , , &
Pages 628-632 | Received 18 Mar 2011, Accepted 12 Jun 2011, Published online: 24 Nov 2011
 

Abstract

Background and purpose Sclerostin is produced by osteocytes and is an inhibitor of bone formation. Thus, inhibition of sclerostin by a monoclonal antibody increases bone formation and improves fracture repair. Sclerostin expression is upregulated in unloaded bone and is downregulated by loading. We wanted to determine whether an anti-sclerostin antibody would stimulate metaphyseal healing in unloaded bone in a rat model.

Methods 10-week-old male rats (n = 48) were divided into 4 groups, with 12 in each. In 24 rats, the right hind limb was unloaded by paralyzing the calf and thigh muscles with an injection of botulinum toxin A (Botox). 3 days later, all the animals had a steel screw inserted into the right proximal tibia. Starting 3 days after screw insertion, either anti-sclerostin antibody (Scl-Ab) or saline was given twice weekly. The other 24 rats did not receive Botox injections and they were treated with Scl-Ab or saline to serve as normal-loaded controls. Screw pull-out force was measured 4 weeks after insertion, as an indicator of the regenerative response of bone to trauma.

Results Unloading reduced the pull-out force. Scl-Ab treatment increased the pull-out force, with or without unloading. The response to the antibody was similar in both groups, and no statistically significant relationship was found between unloading and antibody treatment. The cancellous bone at a distance from the screw showed changes in bone volume fraction that followed the same pattern as the pull-out force.

Interpretation Scl-Ab increases bone formation and screw fixation to a similar degree in loaded and unloaded bone.

FA planned the study together with PA, performed the experiment, did the statistical evaluation, and wrote the draft manuscript. HI developed the CT applications, performed the measurements and analysis, and assisted in writing. XL and HK assisted in study design and manuscript preparation. PA conceived and planned the study together with FA, and assisted in analysis and writing.

XL and HK are employes of Amgen. PA has served as a consultant to Amgen and Eli Lilly and Company, and has financial interest in bisphosphonate coating of bone implants. The research was funded by Amgen and the Swedish Research Council (VR2009-6725).