Effect of aluminum accumulation on bone and cardiovascular risk in the current era

Abstract

Background The prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era. Aims To detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation. Methods This is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered. Results 275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41–56) vs. 55 (43–61) years; p = 0.026], had lower body mass index [23.5 (21.6–25.5) vs. 24.3 (22.1–27.8) kg/m2; p = 0.017], higher dialysis vintage [108 (48–183) vs. 71 (28–132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0–3) vs. 0 (0–3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176–17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000–1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439–6.804; p = 0.004) and HR = 2.785 (CI: 1.120–6.928; p = 0.028]. Conclusions An elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.

Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

“…Este estudo foi realizado como uma subanálise dos dados do REBRABO 5 , e está relacionado, em parte, a dados publicados anteriormente 4,[6][7][8] . A metodologia detalhada foi descrita em outra publicação [4][5][6][7][8] . Em resumo, o REBRABO é uma coorte prospectiva de pacientes com OR.…”

The Role of Trace Elements in Cardiovascular Diseases

“…Al is known to inhibit more than 300 biological relevant reactions involving kinases or phosphatases, mostly due to its ability to bind to phosphates [ 79 , 80 ]. It mediates the extra mitochondrial release of free oxygen radicals, resulting in Fe-induced lipid peroxidation and protein denaturation [ 81 , 82 ].…”

Exposure Assessment of Essential and Potentially Toxic Metals in Wheat-Based Sweets for Human Consumption: Multivariate Analysis and Risk Evaluation Studies

“…The present study found a DI value of Al in the range of 0.46-0.99 mg from 100 g of sweets (Figure 1). Al is not nutritionally important, and a high concentration may lead to various type of ailments in humans [27,28]. The toxic effects of Al are primarily due to its pro-oxidant activity, which causes oxidative stress, and oxidation of cellular proteins and lipids, ultimately leading to denaturation or conformational or structural alterations.…”

“…The toxic effects of Al are primarily due to its pro-oxidant activity, which causes oxidative stress, and oxidation of cellular proteins and lipids, ultimately leading to denaturation or conformational or structural alterations. Exposure to Al has been associated with the development of Alzheimer's disease [27][28][29]. The brain, bones, and kidney are just a few of the many tissues where Al can build up and cause damage and dysfunction.…”