What bone and cardiovascular consequences are associated with aluminum intoxication and accumulation?

By Dr. Liji Thomas, MDApr 21 2023Reviewed by Lily Ramsey, LLM

A recent article published in the PLOS One Journal aimed to detect the diagnosis of bone aluminum (Al) accumulation and explore the bone and cardiovascular consequences of this accumulation.

Study: Effect of aluminum accumulation on bone and cardiovascular risk in the current era. Image Credit: RHJPhtotos/Shutterstock.com

Background

Aluminum (Al) intoxication had become a matter of acute concern a few decades ago, as it underlay an outbreak of dialysis dementia.

Though it has become much less common, there is still interest in understanding how long-term Al exposure, even at low concentrations, affects the body, particularly bone, and cardiovascular health.

Introduction

Al intoxication causing dialysis dementia was controlled by introducing treated hemodialysis water and banning aluminum-based drugs.

However, in several countries, including Brazil, bone biopsies continue to show evidence of Al accumulation in bone tissue.

This could mean that long-term low-level Al exposure causes false negative results on serum Al testing but presents with chronic disease of bone and the cardiovascular system by affecting mineral metabolism.

Moreover, many chronic kidney disease (CKD) cases worldwide pose a huge challenge for healthcare, which is met at very different levels in different parts of the world.  

Al can cause oxidative damage, affect blood vessel tone, and produce apoptosis of heart muscle cells.

The current study aimed to identify the presence of Al accumulation in the body and its impact on bone and heart health.

The data came from The Brazilian Registry of Bone Biopsy, performed at multiple centers over a follow-up period of approximately three years. The patients whose biopsies were included in this registry included those with

The presence of either bone fracture or major cardiovascular events (MACE) was identified, along with the evidence of Al accumulation in a bone biopsy. The study included 275 individuals.

What did the study show?

Of the 275 individuals, over a third (n=96) of the patients were diagnosed to have Al accumulation in the bones. These patients were younger, with a median age of 50 years, compared to 55 years for the rest of the cohort.

The study thus shows a higher percentage of people with Al accumulation in the bones. This did not, however, appear to affect static bone parameters or the rate of bone fractures, while dynamic bone parameters showed minor differences.

The patients with Al accumulation were also lighter than those without, with a body mass index of 23.5 vs. 24.3 and a longer duration on dialysis at a median of 108 vs. 71 months, respectively.

Symptomatically, they were more likely to present with itching in about a quarter of cases compared to a tenth of the rest of the group. Tendon rupture was identified in 7% vs. 2% of Al-accumulation vs. other patients and bone pain in 2 vs. zero units, respectively.

Previous Al accumulation put the individual at over fourfold risk for current Al accumulation in bone, while the duration of dialysis was also an independent risk factor.

MACE was found in over a third of patients with Al accumulation vs. less than a fifth of those without. Both bone Al accumulation (current or past) and diabetes mellitus were independent risk factors for MACE.

While Al buildup in bone increased the MACE risk over threefold, it was increased by almost the same degree with diabetes mellitus.

What are the implications?

The study's results show that current or prior Al accumulation in the body is linked to a buildup of the metal in bone. This is associated with bone pain, ruptured tendons, and pruritus at a greater frequency than controls.

Moreover, the accumulation of Al is also linked to minor disturbances in bone mineralization but has a minimal association with changes in renal osteodystrophy.

Both bone Al accumulation and diabetes mellitus were shown to predict a higher risk of MACE independently. Serum Al accumulation does not show the actual levels of Al in the body tissues and may explain the relatively high number of individuals with bone Al deposition.

We are proposing the new term "Al bone accumulation", instead of "Al intoxication", to refer the identification of Al in bone associated with non-severe symptoms (or subclinical manifestations) and outcomes."

This should be considered in all CKD patients so that it may be properly treated once identified. In CKD patients, preventive measures, including better quality control of hemodialysis water, and avoiding drugs containing significant amounts of aluminum, should be introduced and monitored.