Modulation of bone mass, strength, and turnover by a new benzamide compound, DU-6712, in adjuvant-induced arthritic rats.
To assess the reductions in bone mass, strength, and turnover in adjuvant-induced arthritic rats and to examine the effect of a new benzamide compound, DU-6712, on these parameters, a 28-day dosing experiment was performed using 8-week-old female Lewis rats. Arthritis was induced by injecting the adjuvant into the hind paw. The age-dependent increases in the body weight, lumbar bone mineral content and density (BMC and BMD) and compressive strength were disturbed in the arthritic rats. At 14 days, the histomorphometric parameters of bone formation (BFR/BS and BFR/BV) and the serum osteocalcin levels were significantly reduced compared with the baseline controls. However, the BMC values corrected for body weight did not differ significantly between the arthritic and normal rats, and the bone minerals were not reduced compared with the baseline controls. At 28 days, the parameters of bone minerals and strength of the lumbar body in the arthritic rats, both with and without correction for body weight, were significantly reduced compared with the baseline controls. The trabecular mineralizing surface remained significantly reduced and the osteoclast numbers were increased. DU-6712 at the doses of 5, 15, and 45 mg/kg, orally administered daily from the start of the experiment, significantly prevented the development of the chronic paw edema at 28 days. The reductions in the parameters of bone minerals, strength, and trabecular bone formation, and the increase in osteoclast number were alleviated by this agent. Age-dependent increases in the lumbar height, disturbed by the adjuvant injection, were also maintained. These data indicated that a 28-day period is necessary to obtain sufficient reductions in the bone mass and strength of the lumbar body concerning the model of secondary osteoporosis in adjuvant arthritic rats. DU-6712 was able to prevent these reductions by modulating the bone turnover in this arthritis model.
Uchiyama
Y
Y
New Product Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., 1-16-13, Kita-Kasai Endogawa-ku, Tokyo-134, Japan.
Takamori
H
H
Miyama
K
K
Takano
E
E
Nakajima
H
H
Sato
T
T
Nakamura
T
T
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001549:Benzamides / Q000008:administration & dosage*; D001835:Body Weight; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D008159:Lumbar Vertebrae; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew
D001549:Benzamides; D015675:Osteocalcin