Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice

The administration of either Pentoxifylline (PTX), a methylxanthine derivat ive and an inhibitor of cyclic AMP (c-AMP) phosphodiesterases (PDEs), or Ro lipram, an inhibitor specific to type-4 PDE (PDE4) in normal mice, signific antly increased both cortical and cancellous bone mass. Vertebrae and tibia e from mice treated with PTX or Rolipram were analyzed by means of bone den sitometry and histomorphometry, The results revealed that both PTX and Roli pram increased bone mass in normal mice mainly through the acceleration of bone formation. These findings suggest that both PTX and Rolipram can enhan ce physiological bone formation and thereby increase bone mass in normal mi ce. The possibility that these agents may be of value for the treatment of osteoporosis is discussed. (C) 2000 by Elsevier Science Inc. All rights res erved.