Fracture status in middle-aged individuals with early CKD: cross-sectional analysis of the CARTaGENE survey.

Whether early chronic kidney disease (CKD) is associated with fracture in middle-aged adults is unclear. In a cross-sectional analysis of the CARTaGENE survey, we observed that early CKD was not associated with increased fracture, did not modify the association between calcaneal QUS and fracture, but modified the association between clinical, pharmacological parameters and fracture. INTRODUCTION: The association between advanced CKD and increased fracture risk is well described. However, whether early CKD is associated with increased fractures, especially in middle-aged adults, is unclear. We aimed to assess if early CKD is associated with increased fracture status and whether early CKD status modifies the association between calcaneal quantitative ultrasound parameters, clinical, pharmacological parameters, and fractures. METHODS: Cross-sectional analysis of CARTaGENE, a population-based survey of 40- to 69-year-old individuals. Individuals with CKD (stage 2, estimated glomerular filtration rate [eGFR] 60-89 ml/min/1.73 m2; stage 3, eGFR 30-59) were compared to non-CKD individuals (eGFR > 90). Fracture status (excluding face, toe, hand, and patella) was identified through a questionnaire at baseline. Calcaneal quantitative ultrasound (QUS) was measured in each participant. RESULTS: A total of 17,608 individuals (656 CKD stage 3; 8227 stage 2; 8725 non-CKD) were included. CKD stage 2 and 3 individuals (mean eGFR 78 and 53 ml/min/1.73 m2) were older and had more diabetes, cardiovascular disease, and hypertension. Fracture status prevalence was 14.9% in CKD stage 3, 10.8% in CKD stage 2, and 9.0% in non-CKD individuals. Fracture status prevalence was similar between CKD and non-CKD individuals when stratified by age or after adjustment for demographic and clinical parameters. QUS stiffness index was associated with fracture status in both CKD stage 3 (standardized odds ratio [sOR] = 1.525 [1.200 to 1.939] per 1 SD decrease), stage 2 (sOR = 1.415 [1.310 to 1.530]), and non-CKD individuals (sOR = 1.477 [1.361 to 1.602]). The associations between blood pressure, antihypertensive, and fracture status followed a U-shape throughout the progression of CKD. CONCLUSIONS: CKD stage 3 was not associated with an increase in fracture status. QUS parameters were similarly associated with fracture status in patients with and without CKD.

FGF23-klotho axis, bone fractures, and arterial stiffness in dialysis: a case-control study.

We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease. Therefore, we aimed to assess whether these markers are associated with fractures, bone metabolism, and vascular stiffness in dialysis patients. METHODS: In a prospective hemodialysis cohort, where plasma samples and vascular assessment were performed at baseline, we matched patients who experienced a fracture during follow-up with sex- and age-matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, α-klotho, FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1-N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic-brachial pulse wave velocity ratio, a blood pressure independent measure of arterial stiffness, was used to assess vascular stiffness at baseline. RESULTS: We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a median follow-up of 42 months and a median age of 72 years. In multivariate Cox regression models, high FGF23 levels were associated with increased fracture incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). α-Klotho levels were associated with bone formation but not resorption markers. In both univariate and multivariable adjusted models, α-klotho levels were inversely associated with the aortic-brachial pulse wave velocity ratio (ß = - 0.070; 95% CI - 0.133, - 0.006). CONCLUSIONS: These results suggest a role for FGF23/klotho axis on bone and vascular metabolism in dialysis populations.