title: Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Scl-Ab increases bone formation and screw fixation to a similar degree in loaded and unloaded bone.
authors: Orthopaedics Division, Department of Clinical and Experimental Medicine, Faculty of Medicine, Linköping University, Sweden. fredrik.agholme@liu.se
authors: Fredrik
authors: F
authors: Agholme
authors: Hanna
authors: H
authors: Isaksson
authors: Xiaodong
authors: X
authors: Li
authors: Hua Zhu
authors: HZ
authors: Ke
authors: Per
authors: P
authors: Aspenberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001863:Bone Screws; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology*; D005819:Genetic Markers / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat