Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice.

BACKGROUND: Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice. METHODS: Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration. RESULTS: Aging resulted in urine ca2+ excretion, a decrease in bone ca2+ content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice. CONCLUSION: These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.

Markers of Bone and Cartilage Turnover.

Over the past few decades, scientists have been trying to identify tissue-specific markers that would help to better understand the pathogenesis of bone and cartilage diseases and could be used clinically for the screening, diagnosis and follow-up of bone or joint diseases. Historically, only a few components known to be involved in bone, mineral or cartilage turnover were available for this purpose (e. g., urine hydroxyproline, serum and urine calcium and phosphate levels). However, since most if not all of these substances have wider biological functions beyond bone, mineral and cartilage metabolism, their clinical value as tissue-specific markers was limited. Hence, there was a need to identify more specific indices of bone and cartilage metabolism. Since the 1980s, a number of collagenous and non-collagenous breakdown products as well as cell-specific enzymes have been discovered and developed into markers of musculoskeletal tissue metabolism. This review describes their chemical and biological function, available analytical methods and possible clinical applications.