Osteoporosis as a manifestation of genetically determined syndrome of accelerated aging in OXYS rats

Abstract

Osteoporosis is a systemic disease of the skeleton resulting in a decrease in bone mass, disorder of the bone tissue structure, and increase in the risk of fractures. Its pathogenesis is associated with age-related disorders of the bone tissue remodeling process, but this is not completely known. It has been demonstrated that OXYS rats are a promising model for the investigation of osteoporosis pathogenesis. In the present study, remodeling processes have been compared between senescence-accelerated OXYS rats and Wistar rats (as a control) at ages from 10 days to 24 months. The content of parathyroid hormone (PTH) and osteocalcin (OC), a marker of osteogenesis, in the blood, as well as resorption markers (collagen metabolites pyridinoline (PYD) and deoxypyridinoline (DYD) in the urine and C-terminal telopeptides of α-strain of type I collagen (C-TN) in the blood serum) has been estimated. No differences between strains in the level of the bone metabolism markers at an age of 10 days have been detected. At an age of 3 months, in the OXYS rats the C-TN level in blood, as well as the PYD and DYD level in the urine, increased; at an age of 12 months, the OC decreased, accompanied by further growth of the resorption markers; at an age of 17 months, the PTH decreased. Thus, the dominance of resorption over the bone formation in the OXYS rats occurs at a young age. But, according to the histological studies, as opposed to senile osteoporosis, osteocytes alone (not osteoclasts) to a considerable degree provide the increased resorption of the bone tissue. Intensification of the resorption causes disorder of the bone tissue structure: at an age of 21 months, the volume of the spongy tissue and the width of the trabeculae in the vertebra of the OXYS rats are 74% and 39% smaller than in the Wistar rats.