Bone Abstracts

Objectives: A role for glucose-dependent insulinotropic polypeptide (GIP) in controlling bone mass and strength has previously been reported. However, the rapid degradation of GIP in the bloodstream by the dipeptidyl peptidase-4 enzyme precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed. The aim of the present study was to investigate the effects of 28-day treatment with N-AcGIP on bone microarchitecture and strength in rats.

Materials and methods: Twelve copenhagen rats were randomly allocated to vehicle- or N-AcGIP-treated groups. All procedures were approved by the local animal care and use committee. Trabecular and cortical bone microarchitectures were studied by high resolution microCT whilst bone remodeling markers were assessed in plasma by ELISA. Intrinsic material properties were studied by nanoindentation in trabecular and cortical bone. Bone mineral and collagen properties were assessed by quantitative backscattered electron imaging and Fourier-transformed infrared microscopy. Non-parametric Mann–Whitney U test was used to compare differences between groups.

Results: Compared to vehicle-treated animals, N-AcGIP treated rats did not exhibit modifications of trabecular or cortical microarchitecture. These results were further confirmed with no modification in the circulating levels of either CTx or osteocalcin between the two groups. Intrinsic material properties were improved only in the cortical bone of N-AcGIP-treated animals, with significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%). Furthermore, the mineralization degree of the bone matrix was increased only in cortical bone with significant augmentation (9%) in Ca-peak and Ca-mean. Collagen maturity was also modified in cortical bone matrix with an augmentation of 13%.

Conclusions: Overall, 4 weeks treatment with the GIP mimetic (N-AcGIP) led to improved bone material properties in cortical bone of rats. The use of N-AcGIP might represent an alternative exciting treatment option for bone pathologies with decreased material properties, such as osteoporosis.