Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats.
The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague-Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites.
Tian
XiaoYan
X
Radiobiology Division, University of Utah School of Medicine, Salt Lake City, UT 84108-1218, USA.
Setterberg
Rebecca B
RB
Li
Xiaodong
X
Paszty
Chris
C
Ke
Hua Zhu
HZ
Jee
Webster S S
WS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001853:Bone Marrow / Q000033:anatomy & histology / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D005260:Female; D005819:Genetic Markers / Q000276:immunology*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat