Abstract
Teriparatide (TPTD) is an anti-osteoporotic human PTH analogue that improves bone mass and biochemical properties of bone collagen deeply involved in the strength and quality of bone. However, visualization and quantification of topological properties of bone collagen have long been expected as a diagnostic approach for bone quality, but not well established. This study established a novel combinatorial approach of advanced nonlinear optics imaging (SHG: Second Harmonic Generation) and AI-based automatic morphometrical recognition method.
We applied cynomolgus monkeys as a model animal to fill the critical gap between human and conventional rodent models in terms of bone metabolism and its pharmacological evaluation. TPTD (low dose group: 1.2 µg /kg, high dose group: 6.0 µg /kg) was administered once a week for 18 months to ovariectomized monkeys as an osteoporosis model.
After the TPTD administration for 18 months, the 7th lumbar vertebrae of cynomolgus monkeys were dissected and analyzed by bone morphometry and quantitative SHG imaging.
In the secondary trabeculae of vertebral bone, where remodeling was active, the linearity of collagen fibers and bundles was decreased by OVX, however, recovered by TPTD administration in a dose-dependent manner.
This analysis enables us to visualize and quantify the topological properties of bone collagen fibers and bundles. Moreover, not only the biochemical properties of collagen but the topological properties of collagen fibers contribute to improving the osteogenic effect of TPTD.
