Inhibitory effects of dabigatran etexilate, a direct thrombin inhibitor, on osteoclasts and osteoblasts.

INTRODUCTION: Anticoagulants are widely used in orthopedic surgery to decrease the risk of deep vein thrombosis. While significant bone impairment is induced by long-term heparin therapy, little is known about the effects of direct oral anticoagulants (DOACs). Herein, we investigated the effects of dabigatran etexilate (Pradaxa®), a DOAC inhibitor of thrombin, on bone cells using in vitro and ex vivo cell culture models. MATERIALS AND METHODS: Osteoblasts and osteoclasts exposed to different concentrations of dabigatran etexilate and untreated cells were assayed for cell differentiation and activity. Favorable osteogenic conditions for osteoblasts were tested using titanium with nanotopography (Ti-Nano). In addition, mice treated with a dabigatran etexilate solution had bone marrow cells analyzed for the ability to generate osteoclasts. RESULTS: Dabigatran etexilate at concentrations of 1 µg/mL and 2 µg/mL did not impact osteoclast or osteoblast viability. The drug inhibited osteoclast differentiation and activity as observed by the reduction of TRAP+ cells, resorption pits and gene and protein expression of cathepsin K. Consistently, osteoclasts from mice treated with dabigatran showed decreased area, resorptive activity, as well as gene and protein expression of cathepsin K. In osteoblast cultures, grown both on polystyrene and Ti-Nano, dabigatran etexilate reduced alkaline phosphatase (ALP) activity, matrix mineralization, gene expression of ALP and osteocalcin. CONCLUSIONS: Dabigatran etexilate inhibited osteoclast differentiation in ex vivo and in vitro models in a dose-dependent manner. Moreover, the drug reduced osteoblast activity even under optimal osteogenic conditions. This study provides new evidence regarding the negative overall impact of DOACs on bone cells.

Association between obesity and adipokines levels in saliva and gingival crevicular fluid: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis aimed to compare adipokines' levels in gingival crevicular fluid (GCF) and saliva between individuals with obesity and individuals without obesity. METHODS: Computerized searches were conducted in four electronic databases (PubMed, Medline via Ovid, Web of Science, and Scopus). Manual searches and a Google Scholar search, limiting the search to the first 100 hits, were also conducted. Two calibrated authors performed the study selection, data extraction, and quality assessment of included articles. The quality of the included articles was evaluated using the University of Adelaide Tool. RESULTS: The electronic searches retrieved 929 titles/abstracts. Following the removal of duplicated references, 613 titles/abstracts were assessed. Thirty-four articles were included. Meta-analysis demonstrated that tumor necrosis factor-α (TNF-α) concentration in saliva was statistically increased in individuals with obesity compared with individuals without obesity (P < 0.05). By contrast, the meta-analysis showed no difference in the concentrations of resistin, adiponectin, leptin, ghrelin, and interleukin 6 in saliva and of resistin, adiponectin, leptin, interleukin 6, interleukin 8, tumor necrosis factor α, and plasminogen activator inhibitor 1 in GCF between individuals with and without obesity (P > 0.05). CONCLUSIONS: Individuals with obesity presented higher levels of TNF-α in saliva than individuals without obesity. TNF-α in saliva sampling may be a helpful marker for obesity. For the other adipokines, no difference was observed, but the limited availability and heterogeneity of data do not allow us to assertively state whether changes of adipokines in GCF and saliva are associated with obesity.