The potential relationship between non-alcoholic fatty liver disease and osteoporosis in type 2 diabetes mellitus

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a major challenge of public health cares in China nowadays, is suggested to have strong association with osteoporosis, which is the most important cause of osteoporotic fracture in senior. With the increasing senior population in China, the incidence of type 2 diabetes mellitus (T2DM) also grows dramatically, and T2DM patients have a higher prevalence of NAFLD than the general population. The research focused on demonstrating the correlation between NAFLD and osteoporosis in T2DM is scanty. Objective: To investigate the clinical significance of correlation between NAFLD and osteoporosis in T2DM and identify other associating factors for osteoporosis. Moreover, to evaluate the potential influential factors for the relationship between NAFLD and osteoporosis. Method: The present study enrolled 1328 T2DM patients from the first affiliated hospital of Wenzhou Medical University that is located in eastern part of China from October 2007 to February 2015. All the basic information of patients was collected from the hospital medical record system and telephone-interviews. Univariate analysis stratified by gender was preliminarily used to compare the differences between patients with or without NAFLD. Multivarible logistic regression analyses were utilized to further examine the association between NAFLD and osteoporosis. In addition, the male and female patients were divided into 2 age groups (age < 65 and age ≥ 65) and 5 metabolic groups (group 1 without metabolic items, group 2 with one metabolic items, group 3 with two metabolic items, group 4 with three metabolic items and group 5 with four metabolic items), and further analysis was performed. Results: A total 1328 T2DM patients, including 618 (46.5%) females and 710 (53.5%) males, with mean age 63.18 years old, were enrolled in the present study. The incidence of NAFLD and osteoporosis was 46.2% (614/1328) and 10.7% (142/1328), respectively. Osteoporosis was more prevalented in overall and male T2DM patients with NAFLD than counterparts without NAFLD in univariate analysis (overall 55.6% vs. 45.2%, P = 0.018; male 10.7% vs. 2.56%, P < 0.001 respectively). Logistic regression analysis found that NAFLD was an significant independent predictor for osteoporosis in overall T2DM patients (1.455, 95% 1.018-2.080, P = 0.040) and male T2DM patients (4.460, 95% 2.043-9.738, P < 0.001). When startified by age, osteoporosis was significantly associated with age ≥ 65 years in female T2DM patients (P ≤ 0.001), but not male patients (P = 0.182). Meanwhile, NAFLD was associated with male T2DM patients in both age < 65 and ≥ 65 years old (P = 0.001 and P = 0.003, respectively), but not in female patients with age < 65 and ≥ 65 years old (P = 0.993 and P = 0.305, respectively). In the subgroup analysis of the 5 metabolic groups, the incidence of osteoporosis was significantly higher in male T2DM patients with three or more metabolic items (P = 0.001 and P = 0.011). Meanwhile, NAFLD was only associated with osteoporosis in male T2DM patients with two and three metabolic items (P = 0.039 and P = 0.040, respectively). Male T2DM patients with NAFLD and metabolic items ≥ 2 had significantly higher OR than those without NAFLD and metabolic item < 2 (OR = 6.911 vs. 2.158). Relative excess risk (RERI) 4.346 (95% CI = 0.098-8.791), attributable proportion (AP) = 0.629 (95% CI = 0.236-1.022) and synergy index (SI) = 3.779 (95% CI = 1.620 to 23.05), indicating that the significant interaction of bewteen NAFLD and metabolic factors ≥ 2 with osteoporosis in male T2DM patients. Conclusion: The relationship between NAFLD and osteoporosis was gender-specific in T2DM patients, and NAFLD was independently associated with osteoporosis in male T2DM patients. In addition, osteoporosis was more likely to be found in male T2DM patients with three or more metabolic items. An additional interaction of NAFLD and metabolic items ≥ 2 with osteoporosis risk was found, so Bone mineral density (BMD) test may be recommended to perform in these male T2DM patients.published_or_final_versionPublic HealthMasterMaster of Public Healt