Causal Association Between Primary Biliary Cholangitis and Osteoporosis: A Mendelian Randomization Study.

Background: As the prevalence of osteoporotic fractures increases, impacting the health of the aging population significantly, understanding the genetic link between chronic diseases such as primary biliary cholangitis (PBC) and osteoporosis (OP) is crucial. Despite existing research, the direct genetic relationship between these conditions remains unclear.

Materials and methods: This study used a two-sample Mendelian randomization approach, drawing on the largest available genome-wide association studies. Instrumental variables were selected based on single nucleotide polymorphisms to explore the genetic correlations affecting the association between PBC and OP. This method helps overcome the limitations of traditional observational studies by reducing confounding factors and preventing reverse causation.

Results: The results, primarily derived from the inverse variance weighted method along with MR-Egger and weighted median supplementary methods, demonstrated a significant causal link between the genetic markers associated with PBC and an increased risk of OP. Sensitivity analyses reinforced these findings, affirming the robustness of the genetic associations.

Conclusion: These findings highlight the genetic underpinnings that potentially link PBC to an increased risk of OP, suggesting that genetic factors play a significant role in the progression of chronic diseases. This knowledge could lead to better prevention and treatment strategies for OP, emphasizing the need for integrated treatment approaches that account for genetic predispositions of patients with chronic conditions. Future research should focus on validating these genetic links further and exploring them as potential therapeutic targets. [Orthopedics. 202;4x(x):xx-xx.].