Aluminum in bone

Subcutaneous injection of rabbits with aluminum chloride daily for 28 days was associated with significant accumulation of aluminum in bone, followed in order by significantly increased aluminum concentrations in renal cortex, renal medulla, liver, testes, skeletal muscle, heart, brain white matter, hippocampus, and plasma (Du Val et al. 1986). Because the brain tissue of treated rabbits had the lowest aluminum concentrations of the tissues evaluated, the authors suggested that there was a partial blood-brain barrier to entry of aluminum. 

Recent measurements of aluminum concentrations in human tissues for estimation of exposures are primarily limited to bone and brain tissues (Nieboer et al. 1995). Background levels of aluminum in bone are in the order of 1-3 g/g (ppm, dry weight). These authors also reported that background aluminum levels in brain tissues (primarily grey matter) of healthy individuals typically ranges from 1 to 3 g/g (ppm, dry weight) or <0.5 g/g (wet weight). 

Considering more complex samples or samples that demand a more laborious pretreatment, a more laborious contamination control should be adopted. Slavin and coworkers [104], in order to determine aluminum in bone, wore powderless gloves and used tantalum knives and scrapers (made from ultra-pure tantalum, relatively free from aluminum) to remove adhering tissue from bone. They also used a diamond-disc saw to cut small segments of the sample for analysis, besides using only plasticware and sub-boiling distilled HN03. 

Visser W, Van de Vyver, Verbueken A, Lentferink M, Van Grieken R, De Broe M (1984) The localization of aluminum in bone by means of histochemical and laser microprobe mass analytical methods. Calcif Tissue Int 36 S22. 

The most dramatic consequence of sHPT is alterations in bone turnover and the development of ROD. Other complications of CKD can also promote ROD. Metabolic acidosis decreases bone formation and aluminum toxicity causes aluminum uptake into bone in place of calcium, weakening the bone structure. The pathogenesis of sHPT and ROD are depicted in Fig. 23-5. 

Aiuminum-containing antacids - Constipation (may lead to intestinal obstruction) aluminum-intoxication osteomalacia and hypophosphatemia accumulation of aluminum in serum, bone, and the CNS (aluminum accumulation may be neurotoxic) encephalopathy. 

The neurotoxic effects of aluminum were first observed in people undergoing dialysis for treatment of kidney failure. This syndrome, called dialysis dementia, starts with speech disorders and progresses to dementia and convulsions. Symptoms corresponded with elevated aluminum levels commonly found in bone, brain, and muscle following 3 to 7 years of treatment. Elevated levels of aluminum were also found in the brains of people suffering from Alzheimer s disease. Despite considerable research, it is not clear if the aluminum accumulation in the brain is a cause of Alzheimer s disease or a result of changes in the brain associated with the disease. 

The major inorganic ions in bone mineral are calcium, phosphate and carbonate, with lesser amounts of magnesium, sodium, potassum, chloride, and fluoride66). Traces of iron, copper, lead, manganese, tin, aluminum, strontium, and boron have also been detected67). 

The toxicity of aluminum has been recognized most clearly by the development of bone disease caused by deposition of A1 in bones of patients on hemodialysis and in infants on intravenous therapy/ 6 Excessive A1 in the water used for dialysis may also cause brain damage. Dietary aluminum may be one cause of Alzheimer s disease/ h but this is controversial as is a possible role of aluminum in vaccines in causing inflammation in muscle.1) Solubilization of soil aluminum by acid rain has been blamed for the decline of forests in Europe and North America,) for the death of fish in acid waters,k and for very large reductions in yield for many crops/ An aluminum-resistant strain of buckwheat makes and secretes from its roots large amounts of oxalate which binds and detoxifies the Al3+ ions. ... 

A less common circumstance leading to hypercalcemia is development of a form of osteomalacia characterized by a profound decrease in bone cell activity and loss of the calcium buffering action of bone. In the absence of kidney function, any calcium absorbed from the intestine accumulates in the blood. Therefore, such patients are very sensitive to the hypercalcemic action of l,25(OH)2D. These individuals generally have a high serum calcium but nearly normal alkaline phosphatase and PTH levels. The bone in such patients generally has a high aluminum content, especially in the mineralization front, which may block normal bone mineralization. These patients do not respond favorably to parathyroidectomy. Deferoxamine, an agent used to chelate iron (see Chapter 58 ... 

Exposure to aluminum is usually not harmful. Aluminum occurs naturally in many foods. Factory workers who breathe large amounts of aluminum dusts can have lung problems, such as coughing or changes that show up in chest X-rays. The use of breathing masks and controls on the levels of dust in factories have eliminated this problem. Some workers who breathe aluminum dusts or aluminum fumes have decreased performance in some tests that measure functions of the nervous system. Some people who have kidney disease store a lot of aluminum in their bodies. The kidney disease causes less aluminum to be removed from the body in the urine. Sometimes these people developed bone or brain diseases that doctors think were caused by the excess aluminum. Some studies show that people exposed to high levels of aluminum may develop Alzheimer s disease, but other studies have not found this to be true. We do not... 

Children may be exposed to high levels of aluminum in drinking water. Brain and bone disease have been seen in children with kidney disease. Bone disease has also been seen in children taking some medicines containing aluminum. Animals exposed to aluminum appeared weaker and less active in their cages, and some movements appeared less coordinated than animals not exposed to aluminum. In addition, aluminum also made some animals unusually sensitive to high temperature. These effects are similar to those seen in adults. It does not appear that children are more sensitive than adults. 

The normal level of aluminum in adult human lungs is about 20 mg/kg wet weight (w/w) and increases with age due to buildup reported normal levels in human bone tissue range from 5 to 10 mg/kg (Allfey 1980 Allfey et al. 1980 Coumot-Witmer et al. 1981 Flendrig et al. 1976 Hamilton et al. 1972/73 Tipton and Cook 1963). Low aluminum levels (0.3-0.8 mg/kg w/w) are found in most soft tissue organs, other than the lungs (Hamilton et al. 1972/73 Tipton and Cook 1963). 

To evaluate the retention of aluminum in tissues following oral exposure, rats were fed a diet supplemented with aluminum hydroxide for an intermediate-duration exposure period (Greger and Donnaubauer 1986). Relative to controls, treated rats had increased aluminum concentrations in bone, muscle, and kidneys. Aluminum concentrations in these tissues decreased significantly 3 days after... 

In rabbits given a single intravenous dose of aluminum lactate, aluminum concentrations did not increase above controls in the cerebellum, white brain tissue, hippocampus, spinal cord, adrenal glands, bone, heart, testes, or thyroid (Yokel and McNamara 1989). Treated animals did have significant increases of aluminum in the liver, serum, bile, kidneys, lungs, and spleen. The liver of exposed rabbits had over 80% of the total body burden of aluminum. Persistence of aluminum in the various tissues, organs, and fluids varied. Estimated half-times of aluminum were 113, 74, 44, 42, 4.2, and 2.3 days in the spleen, liver, lungs, serum, renal cortex, and renal medulla, respectively. The kidneys of treated rabbits also demonstrated a second half-time which exceeded 100 days. 

In the cases in which human aluminum toxicity has occurred, the target organs appear to be the lung, bone, and the central nervous system. No specific molecular mechanisms have been elucidated for human toxicity to aluminum. In animal models, aluminum can also produce lung, bone, and neurotoxicity, as well as developmental effects in offspring. 

The major population at risk for aluminum loading and toxicity consists of individuals with renal failure. In a study by Alfrey (1980), 82% of nondialyzed uremic patients and 100% of dialyzed uremic patients had an increased body burden of aluminum. The decreased renal function and loss of the ability to excrete aluminum, ingestion of aluminum compounds to lessen gastrointestinal absorption of phosphate, the aluminum present in the water used for dialysate, and the possible increase in gastrointestinal absorption of aluminum in uremic patients can result in elevated aluminum body burdens. The increased body burdens in uremic patients has been associated with dialysis encephalopathy (also referred to as dialysis dementia), skeletal toxicity (osteomalacia, bone pain, pathological fractures, and proximal myopathy), and hematopoietic toxicity (microcytic, hypochromic anemia). Pre-term infants may also be particularly sensitive to the toxicity of aluminum due to reduced renal capacity (Tsou et al. 1991)... 

For example, DFO treatment has been used to facilitate the removal of aluminum from bone and its entry into the blood where it can be removed by hemodialysis (Haddad and Winchester 1990). DFO is also used in dialyzed uremic patients for the treatment of neurological, hematopoietic, and skeletal toxicity. It should be noted that the clinical usefulness of DFO is limited by a variety of toxic effects including hypotension, skin rashes, stimulation of fungal growth, and possibly cataract formation. 

Fanti P Effects of aluminum on bone cells in culture Dept, of Veterans Affairs Medical Center Dept of Veterans Affairs Research and Development... 

Ahn H-W, Fulton B, Moxon D, et al. 1995. Interactive effects of fluoride and aluminum uptake and accumulation in bones of rabbits administered both agents in their drinking water. J Toxicol Environ Health 44 337-350. 

Coumot-Witmer G, Zingraff J, Plachot JJ, et al. 1981. Aluminum localization in bone from hemodialyzed patients Relationship to matrix mineralization. Kidney Int 20 375-385. 

Eastwood JB, Levin GE, Pazianas M, et al. 1990. Aluminum deposition in bone after contamination of drinking water supply. Lancet 336 462-464. 

Sharp CA, Perks J, Worsfold M, et al. 1993. Plasma aluminum in a reference population The effects of antacid consumption and its influence on biochemical indices of bone formation. Eur J Clin Invest 23 554-560. 

Woodson GC. 1998. An interesting case of osteomalacia due to antacid use associated with stainable bone aluminum in a patient with normal renal function. Bone 22 695-698. 

Phosphates are important because they affect the absorption of calcium and other elements. The absorption of inorganic phosphorus depends on the amount of calcium, iron, strontium, and aluminum present in the diet. Chapman and Pugsley (1971) have suggested that a diet containing more phosphorus than calcium is as detrimental as a simple calcium deficiency. The ratio of calcium to phosphorus in bone is 2 to 1. It has been recommended that in early infancy, the ratio should be 1.5 to 1 in older infants, 1.2 to 1 and for adults, 1 to 1. The estimated annual per capita intake in the United States is 1 g Ca and 2.9 g P, thus giving a ratio of 0.35. The danger in raising phosphorus levels is that calcium may become unavailable. 

Klein GL, Snodgrass WR, Griffin MP, Miller NL, Alfrey AC. Hypocalcemia complicating deferoxamine therapy in an infant with parenteral nutrition-associated aluminum overload evidence for a role of aluminum in the bone disease of infants. J Pediatr Gastroenterol Nutr 1989 9(3) 400-3. 

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