Effects of a novel non-steroidal anti-inflammatory drug (M-5011) on bone metabolism in rats with collagen-induced arthritis.
The effects of a novel non-steroidal anti-inflammatory drug (NSAID), d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid: M-5011, and other NSAIDs (indomethacin, zaltoprofen and tiaprofenic acid) on bone metabolism in Dark Agouti (DA) strain rats with collagen-induced arthritis were evaluated. M-5011 (1.5 and 4.5 mg/kg) and other NSAIDs (1.5 mg/kg) were administered orally once a day from day 14 to day 35 after collagen immunization. In arthritic rats, paw volume and serum levels of anti-type II collagen antibody were increased on day 21 compared to those in non-immunized rats. M-5011 (4.5 mg/kg), indomethacin and zaltoprofen tended to prevent this increase in paw volume. Elevated urinary pyridinoline and deoxypyridinoline levels were found on days 28 and 35 in arthritic rats. M-5011 (4.5 mg/kg) also tended to prevent the increase in urinary pyridinoline level on day 28, but none of the other NSAIDs affected urinary deoxypyridinoline levels. Bone mineral densities in the hindpaw and vertebrae were also decreased in arthritic rats. M-5011 and tiaprofenic acid prevented this decrease in vertebral bone mineral density. These findings indicate that M-5011 partially inhibits the generalized bone loss accompanying the development of collagen-induced arthritis in rats.
Research and Development Laboratories, Osaka, Japan.
N
N
Murakami
H
H
Takase
T
T
Saito
K
K
Iwata
H
H
Miura
T
T
Naruse
D015502:Absorptiometry, Photon; D000596:Amino Acids / Q000652:urine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000209:etiology*; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000008:administration & dosage*; D005260:Female; D010666:Phenylpropionates / Q000494:pharmacology*; D051381:Rats
D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; C015484:pyridinoline; C104139:2-(4-(3-methyl-2-thienyl)phenyl)propionic acid; C036020:deoxypyridinoline; D003094:Collagen