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

Agholme, Fredrik; Isaksson, Hanna LU ; Li, Xiaodong; Zhu Ke, Hua and Aspenberg, Per (2011) In Acta Orthopedica 82(5). p.628-632
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Orthopedica
volume
82
issue
5
pages
628 - 632
publisher
Taylor & Francis
external identifiers
  • Scopus:84862833571
DOI
10.3109/17453674.2011.625539
language
English
LU publication?
no
id
34906860-4b68-484d-978a-c773026f5ea5 (old id 2277274)
date added to LUP
2012-01-10 15:58:28
date last changed
2016-10-13 04:53:40
@misc{34906860-4b68-484d-978a-c773026f5ea5,
  abstract     = {Background and purpose<br/><br>
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.<br/><br>
Methods<br/><br>
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.<br/><br>
Results<br/><br>
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.},
  author       = {Agholme, Fredrik and Isaksson, Hanna and Li, Xiaodong and Zhu Ke, Hua and Aspenberg, Per},
  language     = {eng},
  number       = {5},
  pages        = {628--632},
  publisher    = {ARRAY(0x91e07a8)},
  series       = {Acta Orthopedica},
  title        = {Anti-Sclerostin antibody and mechanical loading appear to independently influence metaphyseal bone in rats},
  url          = {http://dx.doi.org/10.3109/17453674.2011.625539},
  volume       = {82},
  year         = {2011},
}