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

Icariin from Epimedium brevicornum Maxim promotes the biosynthesis of estrogen by aromatase (CYP19)

“…cGMP and its activated PKG have also been found to regulate osteoblast proliferation and differentiation (Rangaswami et al, 2010). Interestingly, the inhibition of cAMP hydrolysis in osteoblasts by PDE inhibitors, such as pentoxifylline or rolipram, has been found to promote bone formation in vitro and in vivo (Ahlström and Lamberg-Allardt, 2000;Kinoshita et al, 2000). Thus, it is possible that icariin may inhibit PDE5 in osteoblasts to increase intracellular cGMP to activate PKG, or to increase cAMP to activate PKA via cGMP and cAMP signaling cross talks.…”

Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome

“…The bone loss observed after tibia fracture, in the setting of elevated levels of multiple cytokines, is consistent with our current state of understanding of interaction between the immune and skeletal systems. PTX treatment can induce osteoblastic differentiation, stimulate bone formation and increase bone mass in mice (Kinoshita et al 2000;Rawadi et al 2001;Tsutsumimoto et al 2002;Horiuchi et al 2004), and other phosophodiesterase inhibitors have been shown to exert therapeutic effect in different osteopenia models (Robin and Ambrus 1983;Waki et al 1999). In the present study, we observed that chronic PTX treatment had no significant effect on trabecular bone loss after fracture, but there was a significant increase in cortical bone thickness after PTX treatment (Fig 6A), perhaps attributable to its inhibitory effects on phosphodiesterases and the NF-κB pathway.…”

Osteoporosis in diabetes mellitus: Possible cellular and molecular mechanisms

“…Such angiogenesis was due to the fact that the injected BMSC differentiated into new mi crovessels (neovascularization), using intercellular adhe sion molecule1 and vascular cell adhesion protein1 for adhesion and migration [67] .Overall, it is possible that anti diabetic agents with angiogenic activity could be used to enhance blood flow to fracture sites, which may in turn accelerate bone healing, and might also prevent osteo penia/osteoporosis. Conversely, certain rheological drugs, such as pentoxifylline, which increase blood flow and osteoblast activity, might be promising as antiosteoporotic agents in both DM and nonDM patients [68] . In addition to medications, alternative interventions often prescribed to DM patients, such as exercise/physical activity, may be indirectly useful since they are expected to mitigate microangiopathy in bone by increasing neo vascularization and blood flow.…”