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

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Anti-Sclerostin antibody and mechanical loading appear to independently influence metaphyseal bone in rats. / Agholme, Fredrik; Isaksson, Hanna; Li, Xiaodong; Zhu Ke, Hua; Aspenberg, Per.

I: Acta Orthopaedica, Vol. 82, Nr. 5, 2011, s. 628-632.

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Agholme, Fredrik ; Isaksson, Hanna ; Li, Xiaodong ; Zhu Ke, Hua ; Aspenberg, Per. / Anti-Sclerostin antibody and mechanical loading appear to independently influence metaphyseal bone in rats. I: Acta Orthopaedica. 2011 ; Vol. 82, Nr. 5. s. 628-632.

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TY - JOUR

T1 - Anti-Sclerostin antibody and mechanical loading appear to independently influence metaphyseal bone in rats

AU - Agholme, Fredrik

AU - Isaksson, Hanna

AU - Li, Xiaodong

AU - Zhu Ke, Hua

AU - Aspenberg, Per

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

U2 - 10.3109/17453674.2011.625539

DO - 10.3109/17453674.2011.625539

M3 - Article

C2 - 22103277

VL - 82

SP - 628

EP - 632

JO - Acta Orthopaedica

JF - Acta Orthopaedica

SN - 1745-3682

IS - 5

ER -