BMI and body fat distribution play an important role in rotator cuff calcific tendonitis: evidence from retrospective study and Mendelian randomization

Objective: This study aims to investigate whether suspected risk factors for tendinopathy also confer risk for rotator cuff calcific tendonitis (RCCT) through a retrospective and a Mendelian randomization (MR) analysis. Methods: Univariate and multivariate logistic regression analyses were performed, incorporating demographic (age, sex) and key metabolic parameters (body mass index, diabetes, dyslipidemia, hypertension) implicated in tendinopathy. Subsequently, a two-sample MR analysis was carried out to investigate causal relationships. The primary exposure was BMI. To dissect its effect, we further evaluated the causal relationships of body fat percentages in specific regions and grip strength with RCCT. Additionally, MR was used to provide a definitive assessment of the relationship between diabetes and RCCT. Results: Retrospective analysis of 71 patients and 80 controls identified older age, female sex, and higher BMI as independent risk factors for RCCT (all P < 0.05). The MR analysis provided genetic evidence to clarify and extend these findings. First, it ruled out a causal role for either type 1 or type 2 diabetes in RCCT ( P = 0.364 and P = 0.183, respectively). Conversely, it confirmed that higher genetically predicted BMI is a causal risk factor for RCCT ( P < 0.001). This causal effect was further delineated by measures of adiposity. Whole-body fat percentage, trunk fat percentage, waist circumference, and limb fat percentage all showed causal associations with increased RCCT risk. Conclusions: By integrating retrospective clinical analysis with MR, we robustly exclude a causal role for diabetes but establish elevated BMI and specific patterns of body fat distribution (trunk and limb adiposity) as independent and causal risk factors. Furthermore, greater grip strength is identified as a protective factor. These findings highlight that weight management and the maintenance of muscular strength – achievable through sustained physical activity – are central to the primary prevention of RCCT.