Quantification of cortical bone loss and repair for therapeutic evaluation in collagen-induced arthritis, by micro-computed tomography and automated image analysis.
OBJECTIVE
Ex vivo and in vivo micro-computed tomography (micro-CT) combined with a novel image analysis algorithm were used to quantify cortical bone loss and periosteal new bone formation for therapeutic evaluation in a murine model of collagen-induced arthritis.


METHODS
An automated algorithm was created to locate 5 metatarsophalangeal and 3 metacarpophalangeal joints in 3-dimensional micro-CT images of mouse paws for evaluation of joint cortical bone volume (JCBV) within close proximity of the joints as well as cortical bone mineral density and periosteal new bone formation within the paws. For validation, automated estimates of JCBV were compared with radiographic visual scores (RVS) in 4 treatment groups (n = 9 per group): rat anti-mouse CD11a monoclonal antibody, methotrexate (MTX), anti-CD11a plus MTX, and saline only. In a separate study, serial images of hind limbs were evaluated in 2 treatment groups: murine tumor necrosis factor receptor II-Fc fusion protein (mTNFRII; n = 10) and control antibody (n = 7).


RESULTS
Automated estimates of the JCBV were significantly correlated with the RVS (hind paws R = -0.94, front paws R = -0.81, combined R = -0.87). The anti-CD11a group had significantly higher JCBV compared with controls. In the serial study, the automated estimate of JCBV detected significant treatment effects in the mTNFRII-Fc group compared with controls. Cortical bone mineral density was significantly higher in all treatment groups compared with controls.


CONCLUSIONS
Micro-CT combined with a novel image analysis technique (estimation of JCBV) provides a fully automated means to quantify bone destruction in a mouse model of rheumatoid arthritis.
Barck
Kai H
KH
Genentech, Inc., South San Francisco, California 94080, USA.
Lee
Wyne P
WP
Diehl
Lauri J
LJ
Ross
Jed
J
Gribling
Peter
P
Zhang
Yifan
Y
Nguyen
Kathy
K
van Bruggen
Nicholas
N
Hurst
Stephen
S
Carano
Richard A D
RA
D000465:Algorithms; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D001323:Autoantibodies / Q000627:therapeutic use; D015519:Bone Density; D040881:CD11a Antigen / Q000008:administration & dosage / Q000276:immunology; D003094:Collagen; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D010012:Osteogenesis; D014057:Tomography, X-Ray Computed / Q000379:methods*
D001323:Autoantibodies; D040881:CD11a Antigen; D003094:Collagen; D008727:Methotrexate