By applying SNPs as instrumental variables (IVs), the MR method can obtain a robust causal estimate independent of postnatal lifestyle or environmental factors. The identification of single nucleotide polymorphisms (SNPs) associated with common complex diseases has been greatly facilitated by genome-wide association studies (GWAS). Recent studies have extensively applied the Mendelian randomization (MR) approach to provide evidence for the causal relationships between exposures and outcomes. Evaluating the causality between OA and SP may provide new strategies for prevention, diagnosis, and treatment of OA, SP and sarcopenic OA. However, none of the previous studies demonstrated the causality relationship between OA and SP. On the other hand, several molecules released by bone structures can also modulate muscles, such as Indian hedgehog and undercarboxylated osteocalcin. These myokines consequently affect cartilage gene expression in terms of formation and homeostasis. The balance between lean mass and fat mass in muscle would lead to the dysregulation of multiple myokines. With the in-depth study of bone-muscle crosstalk, the researchers found that the relationship between OA and SP can also be mediated biologically. Initially, OA and SP are interconnected by biomechanical factors represented by muscle strength.
Preliminary clinical studies have shown a strong correlation between OA and SP and suggested that one condition can increase the possibility of developing the other, especially in the OA of the lower limbs. Moreover, the coexistence of these two conditions: sarcopenic OA, which is frequently seen in clinical practice, could exacerbate the risk of falls and compromise the quality of life.
Unfortunately, at present, we do not have an effective treatment for these two diseases. As two age-related diseases, the prevalence of OA and SP is annually increasing. Sarcopenia was originally defined in 1989 as the age-related loss of muscle mass, but gradually expanded to include muscle strength, muscle mass and physical performance. The two most common types in clinical practice are knee osteoarthritis (KOA) and hip osteoarthritis (HOA). OA is characterized by the destruction and loss of articular cartilage as its main pathological feature, but all joint tissues and even extra-articular structures are involved in some form. Among them, osteoarthritis (OA) and sarcopenia (SP) are two common diseases. With a worldwide population aging, chronic musculoskeletal disorders have imposed a tremendous burden on society. The present study suggests that SP may have a causal effect on OA through changes in muscle composition rather than muscle strength, while little evidence was provided for the causal effect of OA on SP. The inverse variance weighted (IVW), MR-Egger and weighted median estimator (WME) methods were used to estimate bi-directional causal effects. The instrumental variables for SP and four types of OA: KOA, HOA, total knee replacement (TKR) and total hip replacement (THR) were derived from published large genome-wide association studies (GWAS). MethodsĪ bi-directional two-sample MR was adopted to research the causal relationship between SP and OA. The aim of this study was to investigate the causal associations between OA and SP via a bi-directional Mendelian randomization (MR) approach. Previous studies have shown that osteoarthritis (OA) and sarcopenia (SP) are closely related to each other, but the causal relationships between them have not been established.
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