Abstract

Abstract Background and Aims Chronic Kidney Disease (CKD) patients have a complex physiopathology of bone fragility given the development of mineral bone disorder (CKD-MBD) and are at increased fracture risk [1]. Bone turnover, mineralization, and volume (TMV) classification, as proposed by Kidney Disease Improving Global Outcomes (KDIGO), defines different subtypes of renal osteodystrophy (ROD), and is evaluated through bone biopsies and respective histomorphometric analysis. The impact of these parameters and of different ROD subtypes in fracture occurrence has not been evaluated. We aim to evaluate the incidence of fractures in patients with predialysis CKD and the relationship of ROD subtypes and the impact of bone volume with the occurrence of fractures. Method We conducted a retrospective study that enrolled 54 patients (40-89 years old) followed in a predialysis clinic between 2014-2023. Blood tests, bone biopsies and histomorphometric analysis were performed at the beginning of follow-up. Data from dual x-ray absorptiometry (DXA) scan were collected if available. Information regarding clinical evident fractures was recorded from analysis of clinical registries. Radiographies of the thoracic and/or lumbar spine were evaluated to detect asymptomatic vertebral fractures. Results Median follow-up time was 7.5 ± 3 years. Mean age at the time of bone biopsy was 65.4 ± 9.8 years old and most patients were male (n = 43, 79.6%). The majority had CKD stage 4 (53.7%). During follow-up, 20 (37%) patients progressed to kidney replacement therapy and 5 (9.3%) died. DXA scan was performed in 19 patients (35.2%). Of these, 5 had osteoporosis (T-score ≤-2,5). The histomorphometric analysis showed that 40.7% (n = 22) patients had normal bone histology, 37% (n = 20) low bone turnover with normal mineralization (adynamic bone disease) and 22.3% (n = 12) high bone turnover with normal mineralization (hyperparathyroid bone disease). Two patients sustained clinical evident fractures. Radiographies of 51 patients were reviewed and asymptomatic vertebral fractures were identified in 3 (5.9%). The group that suffered fractures had higher phosphorus levels and these differences were statistically significant (4.1 mg/dL vs 3.5 mg/dL, p = 0.047). None of the patients with osteoporosis diagnosed by DXA scan fractured and bone mineral density (BMD) by DXA was similar between the groups (−1.05 vs −1.04, p = 0.530). The different histomorphometric subtypes and circulating biomarkers did not correlate with the incidence of fractures. Patients with fractures had more frequently low bone volume (40%) than patients who do not sustained fractures (25.5%) but this difference was not significant (p = 0.579). BV/TV was lower in the group that sustained fractures during follow-up (16.1 (11.9-17.2) vs 19.0 (16.2-23.6)) and this achieved borderline significance (p = 0.052). Femoral neck BMD measures in the patients who had an available DXA scan did not show any correlation with BV/TV (r = 0.039, p = 0.874). Conclusion No relationship was found between different ROD subtypes and the incidence of fractures. However, when considering bone volume isolated (but not BMD assessed by DXA), a marginally significant association was found between a low BV/TV value and the occurrence of fractures. High phosphorus levels also associated with fractures and have been previously described as a possible risk factor for fractures not only in CKD patients but also general population [2, 3]. Further studies with a larger population are needed to validate these conclusions with statistical power.

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