Ipriflavone inhibits osteoclast differentiation in parathyroid transplanted parietal bone of rats.
Ipriflavone, a synthetic isoflavone-derived flavonoid, was shown to have inhibitory effect on bone resorption. In order to study its mechanism of action directly on bone, 46 female Wistar rats were divided into six groups and medicated orally for 25 days as follows: groups 1 and 2 were given 1% carboxymethylcellulose solution (vehicle), groups 3, 4, 5, and 6 were administered ipriflavone at doses of 0.178, 0.356, 0.712, and 1.424 mmol/kg/day (suspended in vehicle), respectively. On the 22nd day, parathyroid glands, taken from donor rats, were transplanted in contact with the outer surface of the periosteum of both the right and the left parietal bones of rats from groups 2, 3, 4, 5, and 6. The group 1 rats underwent sham operation. Bone histomorphometry, performed on the ectocranial periosteum of parietal bones, showed that absolute erosion boundary, absolute eroded area, absolute erosion depth, number of tartrate-resistant acid phosphatase (TRAP)-positive polynucleated osteoclasts, and number of TRAP-positive mononucleated cells decreased in ipriflavone-treated rats compared with group 2 rats. The reduction was roughly proportional to the increase of drug dosage and reached statistical significance in rats of groups 5 and 6. The same parameters were extremely low in group 1 rats. Mineral apposition rate did not differ in any of the groups. Significant increase of serum calcium and significant decrease of serum phosphate were found in group 2 rats compared with group 1 rats, whereas no differences from controls were detected in ipriflavone-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Bonucci
E
E
Department of Human Biopathology, La Sapienza University of Rome, Italy.
Ballanti
P
P
Martelli
A
A
Mereto
E
E
Brambilla
G
G
Bianco
P
P
Bufalino
L
L
D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D007529:Isoflavones / Q000494:pharmacology*; D010010:Osteoclasts / Q000187:drug effects*; D010280:Parathyroid Glands; D010294:Parietal Bone / Q000187:drug effects* / Q000637:transplantation; D010710:Phosphates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D016042:Transplantation, Heterotopic
D007529:Isoflavones; D010710:Phosphates; C018986:ipriflavone; D002118:Calcium