Effect of minodronic acid (ONO-5920) on bone mineral density and arthritis in adult rats with collagen-induced arthritis.
OBJECTIVE
To study the effect of minodronic acid (ONO-5920) on bone loss and arthritis in rats with collagen-induced arthritis (CIA) treated according to 2 different schedules.


METHODS
Four groups of female Sprague-Dawley rats (7 months old) were studied: rats without CIA treated with vehicle (controls), CIA rats treated with vehicle (CIA-V), CIA rats treated therapeutically with minodronic acid (CIA-T), and CIA rats treated prophylactically with minodronic acid (CIA-P). Minodronic acid was administered orally at 0.2 mg/kg 3 times a week, beginning 2 weeks after initial sensitization in the CIA-T rats and beginning the day after initial sensitization in the CIA-P rats. Bone mineral density (BMD) was measured by peripheral quantitative computed tomography in the proximal metaphysis and diaphysis of the tibia every 2 weeks until week 8, when the rats were killed. The BMD and bone microstructure of the excised femur were evaluated by dual x-ray absorptiometry and microfocal computed tomography, respectively. Histomorphometry of the proximal tibia was also performed.


RESULTS
In CIA-P rats, the incidence of arthritis and the severity of posterior limb swelling were reduced early after sensitization, and the decrease in BMD was prevented throughout the observation period. Bone and joint destruction evaluated by radiography of the foot was reduced in CIA-P rats. The eroded surface was reduced and the microstructure was maintained in CIA-P rats compared with CIA-V rats. The mineral apposition and bone formation rates were not reduced in the CIA-P rats. In CIA-T rats, however, the inflammation was not suppressed and the inhibitory effect on bone loss was smaller than that in CIA-P rats.


CONCLUSIONS
Minodronic acid suppressed the decrease in BMD and the deterioration of the bone microstructure caused by arthritis. Prophylactic administration of minodronic acid had a preventive effect on arthritis at the early stage, although not throughout the observation period.
Yamane
Itsuro
I
Department of Orthopedic Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
Hagino
Hiroshi
H
Okano
Toru
T
Enokida
Makoto
M
Yamasaki
Daisuke
D
Teshima
Ryota
R
D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D015519:Bone Density / Q000187:drug effects; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D021621:Imaging, Three-Dimensional; D007093:Imidazoles / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D014056:Tomography, X-Ray
D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529