Pradaxa (dabigatran etexilate) is a new anticoagulant, which recently has been approved for clinical use. Dabigatran etexilate (DE) is a direct thrombin inhibitor, which in addition to its effect on blood clotting, may have an anabolic effect on bone. Recently, it has been reported that DE could significantly reduce bone resorption and enhance bone formation resulting in a significant and substantial increase in trabecular bone mass in mice.
The aim of the present study was to investigate whether DE can increase aBMD, bone strength, and microstructure in male and female mice.
A total of 28 male 14-week-old C57BL/6 mice were randomized by weight into four groups: 1. Control 3 weeks; 2. DE 3 weeks; 3. control 6 weeks; 4. DE 6 weeks. An identical design was applied to 26 female C57BL/6 mice. DE was given in the chow (15 mg/g chow) and offered ad libitum. The animals were killed after 3 or 6 weeks, respectively. aBMD and BMC were evaluated with pDEXA, 3D microstructural properties were determined with μCT, and bone strength were determined with mechanical testing. The experiment was approved by the Danish Animal Experiments Inspectorate.
Significant higher tibial and vertebral aBMD (P<0.05) were found in DE-treated female mice, but not in DE-treated male mice after 6 weeks intervention. No significant changes were found in distal femoral epiphyseal or metaphyseal microstructure and vBMD in female or male mice. No significant changes were found in proximal tibial metaphyseal microstructure and vBMD, and no significant changes were found in tibial three-point bending strength and stiffness in female or male mice.
In conclusion, DE increased tibial and vertebral aBMD in female mice, but not in male mice. Furthermore, no effects of DE were found on trabecular bone 3D microstructure and tibial bending strength in either female or male mice.
14 May 2016 - 17 May 2016