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.

Fig 1. Kaplan-Meier curve for MACE according to actual/prior diagnosis of bone Al accumulation (log-rank; p = 0.002).