Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice. Female KO and WT mice aged 8 weeks received either an H1R antagonist (cetirizine) or polyethylene glycol (PEG) for 6 months. At the end of the study, KO mice displayed elevated plasma histamine levels compared to WT. As demonstrated previously, the KO mice also exhibited lower whole body BMD, reduced mechanical bone strength, and impaired bone quality assessed by μCT. No significant differences, however, were found between the KO groups receiving cetirizine or PEG for any of the measured bone parameters. In vitro gene expression analyses of histamine receptors revealed the presence of H1R and H2R both in osteoblasts and osteoclasts, and H3R in late stage osteoblasts. In conclusion, administration of the H1R antagonist cetirizine in a concentration of 3 mg/kg did not rescue the osteoporotic phenotype in H(+) /K(+) ATPase beta subunit KO mice. It can, however, not be ruled out that histamine may influence bone via other receptors. J. Cell. Biochem. 117: 2089-2096, 2016. © 2016 Wiley Periodicals, Inc.

A new wearable assistive device (WAD) was developed to decrease required force on the lumbar spine in static holding tasks. In order to obtain moments on lumbar spine in two conditions, with and without WAD, a biomechanical static model was used for estimation of external moments on lumbar spine. The results of biomechanical models indicated that there was a reduction in the lumbar moment ranging from 20% to 43% using WAD depending on the load and flexion angle. A total of 15 male healthy subjects were tested to experimentally verify the predicted reduction of external moments on the spine by wearing WAD. Normalized electromyography (EMG) of the right and left lumbar and thoracic erector spinae (LES, TES), latissimus dorsi (LD), external oblique (EO), internal oblique (IO) and rectus abdominus (RA) muscles were monitored at three lumbar flexion positions (0°, 30° and 60°) in symmetric posture with three different loads (0, 5 and 15 kg) in two conditions of with and without WAD. The effects of WAD and load were significant for all muscles but the interaction effects were only significant for extensor muscles groups (p < 0.016). Results of statistical analysis (ANOVA) on the normalized EMG while wearing WAD indicated that the muscle activity of right and left LES, TES and LD muscles significantly decreased (p < 0.001). This reduction for right LES, TES, LD muscles at 15 kg load and 60° trunk flexion were 23.2%, 30% and 27.8%, respectively which were in good agreement with the biomechanical model results.

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Nanoindentation test results in the axial direction of mouse femurs were the basis for the current study. Although the majority of the nanoindentation curves showed a reasonable consistency, some curves showed a significantly softer response. Detailed investigation, using focused ion beam-scanning electron microscopy, provided that the softer response is due to subsurface cavities such as lacunae. Finite element models were developed to simulate the nanoindentation of mice femur cortical bone samples with and without the incorporation of a single lacuna underneath the bone surface. Based on the material parameters determined for the cavity-free tissue, numerical simulations were run for different cases of cavity size, shape, and location. Spherical cavities with different size were considered at different distances from the surface. The results showed that subsurface cavities can lead to 50% higher indentation compared to an indentation in cavity-free material. Continuing with ellipsoidal cavities with the center located on the load axis, the results showed a nonlinear dependency of ellipsoid shape. Hence, the shape of the cavity is important for the nanoindentation response. The influence of horizontal and vertical offsets of spherical cavities was studied, thereby the results showed that an increasing horizontal offset caused a decreasing influence of the vertical distance from the surface. In perspective, the present study provides information that may help to get deeper knowledge of nanoindentation load-displacement mechanism taking place in samples with subsurface cavities.

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