The association between primary frozen shoulder and serum lipids may be overestimated: evidence based on retrospective observational studies and Mendelian randomization.

Background: Previous studies have shown that dyslipidemia is significantly associated with primary frozen shoulder and may be a risk factor for the development of primary frozen shoulder. However, these findings may be biased by a number of confounding factors. We investigated the association between serum lipids and primary frozen shoulder by retrospective analysis and two-sample Mendelian randomization (MR) methods. Methods: This retrospective observational study included 284 patients with primary frozen shoulder diagnosed from October 2020 to October 2023 at four centers as the experimental group. Patients with diabetes and thyroid dysfunction were excluded. The control group consisted of age- and sex-matched people who underwent a health checkup. We compared total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) between the two groups. Genetic variants for the serum lipids and frozen shoulder were then extracted from large-scale genome-wide association studies. Causal effects were assessed using Inverse variance weighting (IVW), Weighted median, MR-Egger, simple and weighted models in MR analysis. Results: The analysis showed that after excluding patients with diabetes and thyroid dysfunction, the serum lipids (TC, TG, HDL, and LDL) in the primary frozen shoulder group were no different from those of normal individuals. None of the MR methods found significant causal evidence between them. Conclusions: Dyslipidemia in patients with primary frozen shoulder may be influenced by confounding factors such as diabetes and thyroid dysfunction. These findings deepen our understanding of primary frozen shoulder risk factors.