REDUCTION OF BONE LOSS BY DENBUFYLLINE, AN INHIBITOR OF PHOSPHODIESTERASE-4

Citation
K. Miyamoto et al., REDUCTION OF BONE LOSS BY DENBUFYLLINE, AN INHIBITOR OF PHOSPHODIESTERASE-4, Biochemical pharmacology, 54(5), 1997, pp. 613-617
Citations number
18
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
54
Issue
5
Year of publication
1997
Pages
613 - 617
Database
ISI
SICI code
0006-2952(1997)54:5<613:ROBLBD>2.0.ZU;2-V
Abstract
The effects of denbufylline, a xanthine derivative with selective inhi bitory activity on the phosphodiesterase (PDE) 4 isoenzyme, on bone lo ss in Walker 256/S-bearing rats and on mineralized nodule formation an d osteoclastlike cell formation in bone marrow culture systems were ex amined. Serial oral administrations of denbufylline inhibited the decr ease in the bone mineral density of femurs from Walker 256/S bearing r ats, without influence on the healthy rats. Denbufyllin restored the b one mass and the number of osteoclasts and osteoblasts per trabecular surface in the femur metaphysis. Among PDE inhibitors, only PDE4-selec tive inhibitors increased the number of mineralized nodules and decrea sed the number of osteoclastlike cells in the in vitro bone marrow cul ture systems, and dibutyryl cyclic AMP mimicked these effects in the i n vitro systems. These results suggest that the PDE4 isoenzyme may pla y an important role in bone turnover through cyclic AMP and that its i nhibitors are candidates for therapeutic drugs for the bone loss disea ses. (C) 1997 Elsevier Science Inc.