Bone ultrastructure and x-ray microanalysis of aluminum-intoxicated hemodialyzed patients

Abstract

In hemodialyzed patients aluminum (Al) intoxication may induce osteomalacic lesions which are mainly observed when plasma immunoreactive parathyroid hormone (iPTH) concentrations are low, and osteitis fibrosa absent. In this study, the bone tissue of eight hemodialyzed patients with elevated plasma and bone Al concentrations was examined by histomorphometry, electron microscopy, and x-ray microanalysis. Five patients (group 1) had osteomalacia and minimal osteitis fibrosa, three patients (group 2) had severe osteitis fibrosa. In group 1, Al was concentrated at the mineralizing front, in hexagonal structures measuring 200 to 1,000 A which also contained phosphorus, but not calcium. Hydroxyapatite needles had a normal aspect. Osteoblasts appeared inactive. In group 2, Al was also present at the mineralizing layer of osteoid, but, in these cases, in small clusters next to abnormal calcium deposits. Osteoblasts appeared very active. Their mitochondria contained calcium and phosphorus granules, or amorphous material, measuring 1,500 to 2,000 A, emitting x-rays characteristic for Al and phosphorus. These results suggest that secondary hyperparathyroidism, by stimulating the cellular activity, may increase the uptake and release of Al by the osteoblasts. The presence of Al within the mitochondria of these cells may be one of the factors inducing the mineralization defect.

Relative in Vitro Efficacy of the Phosphate Binders Lanthanum Carbonate and Sevelamer Hydrochloride

“…Aluminum is widely recognized as the most effective phosphate‐binding drug but its use is now generally restricted to ESRD patients who are uncontrolled on other agents, owing to concerns about its toxicity, including dialysis encephalopathy,9, 10 osteomalacia,11, 12 and microcytic anaemia 13. Calcium‐based binders largely replaced aluminum in the 1980s and 1990s and have been the mainstay of treatment for many years 14.…”

Adynamic Bone Disease in Uremia: May It Be Idiopathic? Is It an Actual Disease?

“…It has recently been explained by a primary effect of aluminum on the affinity of PTH receptor which may be related to exchange of aluminum with magnesium at the G protein level [49]. Furthermore, it should be pointed out that Al was found at high concentration in the mitochondria of intoxicated patients, and that this storage may interfere with the calcium fluxes implicated in the extracellular mineral deposition [50],…”

Nutritional Aspects of Aluminium Toxicity

“…The accumulation per se of A1 at the mineralization front of bone may not be responsible for the toxic effect of Al; rather a deleterious effect on osteoblasts (Plachot et al 1984;Lieberherr et al 1987;Ott et al 1987;Blair et al 1989), their precursors (Simmons et al 1991) or, alternatively, inhibitory effects on the production or action of parathyroid hormone (Cann et al 1979;Morrissey et al 1983;Henry et al 1984;Bourdeau et al 1987) or 1,25-dihydroxycholecalciferol (Henry & Norman, 1985;Klein et al 1986) may be responsible for the bone abnormalities. In addition, Al may also contribute to the bone lesion by physically interfering with hydroxyapatite formation (Posner et al 1986) or with calcium phosphate crystal formation (Meyer & Thomas, 1986).…”