The proportion of the elderly population is increasing as life expectancy continues to rise. Consequently, the prevalence of age-related diseases is also increasing, along with the need to develop new approaches and identify novel therapeutic targets for their treatment. With aging
of the musculoskeletal system, the incidence of osteoporosis increases, while the additional presence of muscle weakness, i.e., osteosarcopenia, leads to even more pronounced functional decline and loss of independence in older adults. This represents a burden not only for patients but also for their caregivers and the healthcare system. RUNX1, RUNX2, TGF-β1, and VEGFA are well-known endogenous regulators of bone remodeling. The aim of this study was to investigate whether the expression of these genes, which regulate the formation and function of osteoblasts, influences bone tissue structure in both osteoporosis and osteosarcopenia. We aimed to test the hypothesis that the regulation of
bone formation is more severely impaired in osteosarcopenia than in osteoporosis alone, leading to more pronounced alterations in bone tissue and consequently increased bone fragility. The study included 58 female participants who underwent hip arthroplasty due to a hip fracture.
A total of 55 histological bone tissue samples from osteoporotic and osteosarcopenic patients were prepared and stained with hematoxylin and eosin, as well as Masson’s trichrome stain. Based on microscopic evaluation, the mean bone volume fraction and the average trabecular thickness—two key parameters for assessing bone porosity—were measured. In all participants, muscle mass was assessed using the skeletal muscle mass index, and muscle strength was evaluated using the handgrip strength test. Gene expression in bone tissue was measured using quantitative real-time polymerase chain reaction (qPCR). Statistical analysis was performed using the Mann–Whitney U test, independent samples t-test, and Pearson and Spearman correlation coefficients in the SPSS software.
Our results showed that, compared to osteoporotic patients, osteosarcopenic patients exhibited significantly higher expression of RUNX2 (p = 0,041) and significantly lower expression of VEGFA (p = 0,041). In the osteosarcopenic group, a positive and significant correlation between the expression of these two genes was observed (p = 0,001). Furthermore, in this group, RUNX2 expression significantly correlated with RUNX1 (p = 0,001) and TGFB1 (p = 0,015), while VEGFA expression also correlated with RUNX1 (p = 0,045) and RUNX2 (p = 0,001). Among other associations in osteosarcopenia, a significant correlation between RUNX1 and TGFB1 expression was identified (p = 0,001). In osteoporosis, the relationships between gene expression levels are already well established and were confirmed in our study, specifically the associations between RUNX1 and RUNX2 (p = 0,001), as well as TGFB1 (p = 0,038).
Our findings indicate important differences in the expression of regulatory genes in osteosarcopenia compared to osteoporosis. This is likely due to increased oxidative stress, inflammation, and other processes that are more pronounced in osteosarcopenia due to the additional presence of sarcopenia. Further research is needed to identify the key factors involved in these processes, as these molecules may represent potential targets for more effective treatment of osteosarcopenia and age-related frailty.
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