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Objective: Pathological processes in bone can lead to fatal health consequences. Therefore, it is important to study factors that possibly influence the activity of bone cells. The mast cell is a normal component of bone, storing and producing many potent bioactive substances. One of the most important factors to influence mast cell number, function, and phenotype is the c-kit ligand. A defect of the c-kit receptor leads to mast cell deficiency. In literature oversight, evidence for the importance of mast cells in skeletal homeostasis is compiled., Methods: To investigate the influence of c-kit receptor deficiency on bone mass, geometry, microstructure, and strength, 30 femora of profoundly c-kit receptor deficient mouse mutants and 30 control group animals aged 8-20 weeks were phenotypically characterized using peripheral quantitative computed tomography (pQCT), micro-computed tomography (microCT) and 3-point-bending., Results: The femora of the c-kit receptor and therefore mast cell deficient animals were significantly altered in bone mass and geometry but not in bone density and microstructure. The mutants had a lighter femur with a thinner shape. The lower load bearing capacity of the femora of mast cell deficient mouse mutants is more likely explained by the smaller amount of bone material than due to a change in intrinsic material properties., Technical Considerations: With the little dimensions of mouse bones, it is of prime importance to have precise methods to phenotypically characterize the bone. The pQCT allows the separate assessment and analysis of trabecular and cortical bone density, as well as a statement about bone geometry. Beyond it, the microCT-technique delivers a 3-D analysis of bone microstructure, which so far was only achieved with 2-D histomorphometry. microCT is an efficient alternative to destructive histological preparations allowing further biomechanical testing of the same specimens to also deliver measures for bone strength.

The aim of the present study was the non-invasive, sex-specific measurement of bone mass in bovine growth hormone (bGH) transgenic mice and normal controls with dual energy X-ray absorptiometry (DXA). The transgenic mouse constitutes a suitable animal model to study the influence of growth hormone on the skeletal system. We analysed 28 animals, aged 12 weeks (14 transgenic, 14 controls, 7 male and 7 female, respectively), using a peripheral DXA scanner that had been adapted to the measurement of small animals. At a measurement time of 20 min, the precision (RMS average CV%) was 4.4% for bone mass (BMC), 2.5% for areal bone density (BMD), 0.86% for total body weight and 4.5% for the percentage BMC (relative to body weight). While the absolute bone mass was not significantly different between male and female animals, we found a higher percentage of the BMC relative to the total bone mass in females (+21% in controls, +31% in transgenics; p < 0.01). The absolute bone mass was higher in the transgenic animals (+71% in females and +62% in males; p < 0.01), but relative to the body weight the transgenic females yielded similar and the transgenic males lower values (-7.2%; p < 0.05). Using DXA it is possible to non-invasively determine the mass of mineralised tissue in the mouse with relatively high precision and to effectively discriminate between different groups. Although a strong influence of growth hormone on the absolute bone mass is observed, the results show that this increase is not higher than that of the total body mass.