The association between total bile acid and bone mineral density among patients with type 2 diabetes

Abstract

ObjectiveBile acids have underlying protective effects on bones structure. Long-term diabetes also causes skeletal disorders including osteoporosis, Charcot arthropathy and renal osteodystrophy. Nevertheless, few studies have reported whether bile acid is associated with bone metabolism in diabetics. This study aimed to explore the relationship between total bile acid (TBA) and bone mineral density (BMD) among patients with type 2 diabetes mellitus (T2DM).MethodsWe retrospectively included 1,701 T2DM patients who were hospitalized in Taian City Central Hospital (TCCH), Shandong Province, China between January 2017 to December 2019. The participants were classified into the osteopenia (n = 573), osteoporosis (n= 331) and control groups (n= 797) according to BMD in the lumbar spine and femoral. The clinical parameters, including TBA, bilirubin, vitamin D, calcium, phosphorus and alkaline phosphatase were compared between groups. Multiple linear regression was used to analyze the relationship between TBA and BMD in lumbar spine, femoral, trochiter, ward’s triangle region. A logistic regression was conducted to develop a TBA-based diagnostic model for differentiating abnormal bone metabolism from those with normal BMD. We evaluated the performance of model using ROC curves.ResultsThe TBA level was significantly higher in patients with osteoporosis (Median[M]= 3.300 μmol/L, interquartile range [IQR] = 1.725 to 5.250 μmol/L) compared to the osteopenia group (M = 3.200 μmol/L, IQR = 2.100 to 5.400 μmol/L) and control group (M = 2.750 μmol/L, IQR = 1.800 to 4.600 μmol/L) (P <0.05). Overall and subgroup analyses indicated that TBA was negatively associated with BMD after adjusted for the co-variates (i.e., age, gender, diabetes duration, BMI, total bilirubin, direct bilirubin, indirect bilirubin) (P <0.05). Logistic regression revealed that higher TBA level was associated with increased risk for abnormal bone metabolism (OR = 1.044, 95% CI = 1.005 to 1.083). A TBA-based diagnostic model was established to identify individuals with abnormal bone metabolism (T-score ≤ -1.0). The area under ROC curve (AUC) of 0.767 (95% CI = 0.730 to 0.804).ConclusionOur findings demonstrated the potential role of bile acids in bone metabolism among T2DM patients. The circulating TBA might be employed as an indicator of abnormal bone metabolism.

Prediction of prognosis in patients with ischemic stroke combined with type 2 diabetes mellitus based on serum total bilirubin levels

“…Notably, emerging evidence suggests bilirubin may confer protective vascular and neurological effects via antioxidant, anti-inflammatory and endothelial function improving mechanisms. [47][48][49] Our results demonstrating an association between higher serum bilirubin levels and favorable outcomes in diabetic stroke patients are consistent with these reports. Furthermore, our study provides novel evidence that bilirubin could potentially serve as a prognostic biomarker specifically in the high-risk diabetic population.…”

Cholestyramine alleviates bone and muscle loss in irritable bowel syndrome via regulating bile acid metabolism

“…Some scientists claimed that BAs enhanced osteoblastic differentiation through binding with Farnesoid X receptor 42 and serum BA levels have been proved to have a positive correlation with BMD in postmenopausal women 43 . However, some researchers argued that BAs are risking factors of osteoporosis in primary sclerosing cholangitis (PSC), type 2 diabetes 44,45 . While our research marks a significant stride in this direction, the intricate mechanisms through which BAs affect bone and muscle health, particularly under IBS‐induced stress, remain elusive.…”

“… 43 However, some researchers argued that BAs are risking factors of osteoporosis in primary sclerosing cholangitis (PSC), type 2 diabetes. 44 , 45 While our research marks a significant stride in this direction, the intricate mechanisms through which BAs affect bone and muscle health, particularly under IBS‐induced stress, remain elusive. This knowledge gap signifies the need for extensive future studies focusing on the systemic roles of BAs and the underlying molecular crosstalk in the gut‐musculoskeletal axis.…”

Folic acid supplementation prevents high body fat-induced bone loss through TGR5 signaling pathways

“…18 Bile acids are important nutritional sensors and metabolic integrators, which are important substances for regulating bile acid biosynthesis, lipid and glucose homeostasis, and immune signaling, and play a key role in maintaining metabolic homeostasis. 19,20 Population studies have found that bile acids have a potential protective effect on the bone structure in type 2 diabetes patients and postmenopausal women, 21,22 but the specific mechanism is still unclear. Bile acids are signaling molecules that mainly regulate the metabolic status through the nuclear farnesoid X receptor (FXR) and G-protein coupled receptor 5 (TGR5).…”