Tenofovir Causes Bone Loss via Decreased Bone Formation and Increased Bone Resorption, Which Can Be Counteracted by Dipyridamole in Mice.

摘要: Osteopenia and fragility fractures have been associated with human immunodeficiency virus (HIV) infection. Tenofovir, a common antiviral in HIV treatment, also leads to increases bone catabolism markers decreased BMD children young adults. In murine models cell lines, tenofovir inhibits adenosine triphosphate release decreases extracellular levels. Adenosine A2A receptor inhibit osteoclast formation, increase local concentration dipyridamole, an agent that blocks cellular uptake stimulates new formation as well morphogenic protein 2. We hypothesized regulates resorption by diminishing endogenous levels questioned whether dipyridamole may be useful treatment counteract the deleterous effects of tenofovir. Primary osteoclasts were induced M-CSF/RANKL, number TRAP-positive-cells was studied after challenge alone or combination dipyridamole. Differentiation RT-PCR MAPK/NFkB expression Western blot. Male C57Bl/6 mice treated follows: saline 0.9% (control), 75 mg/kg/day, 25 tenofovir/dipyridamole (n = 10, 4 weeks). Calcein/Alizarin Red-labeling newly formed used, long bones prepared for micro-computed tomography (μCT)/histology. Tenofovir produced dose-dependent differentiation (EC50 44.5nM) reversed (IC50 0.3 μM). increased cathepsin K NFATc1 mRNA effect. Dipyridamole effect on pERK1/2, pp38, NFkB nuclear translocation. Mice lost nearly 10% their body weight (p < 0.001). μCT revealed altered trabecular tenofovir-treated mice, TRAP-staining showed 0.005), Similar results obtained CD68. RANKL-positive cells whereas osteoprotegerin-positive decreased; both These suggest agents concentrations, like might prevent loss following treatment. © 2019 American Society Bone Mineral Research.