Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength of Intact Bones in Adult Male Rats.
We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25 mg/kg, 2 times per week) treatment for 9 weeks. Compared with vehicle control, Scl-Ab treatment significantly improved trabecular and cortical bone mass and microarchitecture at L5 vertebrae and left femora by micro-CT at week 6 and 9. Mechanical testing showed that Scl-Ab treatment resulted in significantly higher stiffness, energy to failure and ultimate load at the femora at week 9. Mineral apposition rate, mineralizing surface and bone formation rate on the trabecular bone in the distal femora was significantly increased in Scl-Ab group at week 6 and 9. The administered Scl-Ab was localized in the osteocytes and beta-catenin was strongly expressed in osteoblasts. Scl-Ab treatment significantly increased serum P1NP level and there was no between-group difference in serum level of CTX-1. In conclusion, Scl-Ab treatment could induce rapid and sustained increase in bone formation, bone mass and bone strength in non-operated bones. Sclerostin inhibition might be advantageous to prevent secondary fracture(s).
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Pui Kit
PK
Suen
Bone Quality and Health Centre, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Tracy Y
TY
Zhu
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Dick Ho Kiu
DH
Chow
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Le
L
Huang
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
Li-Zhen
LZ
Zheng
Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|Bone Quality and Health Centre, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, PR China.|The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University Research Institute in Shenzhen, PR China.
Ling
L
Qin
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001846:Bone Development / Q000276:immunology*; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D016723:Bone Remodeling; D005819:Genetic Markers / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C486031:Sost protein, rat