The effect of Advanced Glycation End Products (AGES) on bone formation

Bone fragility fractures have been a major concern in the health care of elderly populations. One of the major reasons for fragility fracture is that the structure of bone itself may experience age-related changes, which may affect the normal process of bone remodeling and eventually make bone fragile. Adverse changes in the bone matrix through biochemical modifications like Advanced Glycation End Products (AGEs) is one such changes that could increase bone fragility. AGEs modify long-lived proteins (e.g. collagen) in a period of weeks and may affect bone cell activities during the remodeling process. In this study, a unique rat implant model with autograft implants was used to mimic in vivo response of bone formation to the matrix AGEs. Bone cores were first dissected from the proximal tibia, then ribosylated to introduce the matrix AGEs and finally implanted back to the counterlateral tibia to observe the bone formation rate. Comparing the control and treated animals after the third week the control group exhibited many more locations where bone formation takes place. Mineral Apposition Rate (MAR) is found around higher in control group. Consequently, overall bone formation rate was found higher in the control group. These results suggest that AGEs may inhibit osteoblast activities during bone formation in rat tibia. Dependency of bone formation on the location of the implant and on the depth in the implant was also studied in this research to observe any relation between the bone formation regions and their orientation. The current results are suggesting that the location of growth plate and availability of more bone marrow in tibia might have a positive correlation with control samples. Finally nano-indentation test was done to evaluate the mechanical properties of the newly formed bone in the vicinity of the core to study if there is any structural changes occuring due to the effect of AGEs and its impact on the overall strength of the bone, yet the results do not suggest any significant difference in the material properties between the control and treated group of specimen.