Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties.

Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4 weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone.

Comparison of pencil-, fan-, and cone-beam dual X-ray absorptiometers for evaluation of bone mineral content in excised rat bone.

The aim of the present study was to assess the reproducibility and accuracy of measurements done on excised rat bone with three different generations of densitometers: Hologic QDR2000 pencil beam, Hologic QDR4500 fan beam, and Lunar PIXImus cone beam. The coefficients of variation for repeated measurements of bone mineral content (BMC) were 0.62 and 0.85% for pencil beam, 1.73 and 3.59% for fan beam, and 0.70 and 1.52% for cone beam for femur and tibia, respectively. BMC and ash weight were linearly correlated: 0.998 for pencil, 0.984 for fan, and 0.995 for cone beam. However, the three densitometers overestimated BMC by 10.9, 12.6, and 3.1%, respectively, and the overestimation was found to be dependent on the net BMC. The highest coefficient of correlation was found between BMC measurements from pencil and cone beam (r = 0.995). Data from cone-beam DXA were, respectively, 8.8 and 9.2% lower than those from penciland fan-beam DXA. We conclude that the three DXA instruments precisely and accurately measure BMC in excised rat bone; however, DXA overestimates BMC with a dependence on the bone ash weight. This dependence was less pronounced with the cone-beam technology.