Evidence for a toxic effect of aluminum on osteoblasts: A histomorphometric study in hemodialysis patients with aplastic bone disease

To evaluate the potential role of aluminum (Al) in a subset of dialysis patients with aplastic bone disease, we have studied tetracycline-labeled bone biopsies of 32 patients (22 males and 10 females, 45–73 years) on maintenance hemodialysis. Selection criteria included normal resorption surfaces (RS) and osteoid thickness. Eleven patients (Group I) had no stainable bone Al (Al -; 61.7 ± 7.2 years) and 21 (Group II) had stainable bone Al (Al +; 57.7 ± 6.8 years). Serum Al was normal to slightly elevated in Group I, but significantly higher in Group II (p < 0.01). Al surfaces (AlS), undetectable in Group I, were 67.8 ± 17.9% in Group II. Bone Al content (BAC) was much lower in Group I than in Group II (14.8 ± 3.7 vs. 113.8 ± 100.2 μg/g, p < 0.01), but higher in Group I than in controls (p < 0.05). Extensive thin osteoid seams were present in Group II. AlS was correlated with OS (r = 0.56, p < 0.001) and OV (r = 0.48, p < 0.01). Labeled surfaces were decreased in both groups. Labeled osteoid surfaces (TLS/OS) were below 2 SD of the mean control values in 96% of patients and calcification rate (CR) was depressed below 0.20 μm/day in 44% of patients. Bone formation rate (BFR) was strikingly depressed, values being below one SD of the mean control value in 92–100% of patients at both levels and below 2 SD of the mean in 82% of patients at BMU levels. Mineralization lag time (OMP) was markedly prolonged above 2 SD of controls in 89% of patients. A major observation was in the extent of osteoblast osteoid surfaces (OblS/OS) which was found significantly different in Group I (34.2%) than in Group II (15%) (p < 0.001); these differences were consistently found in osteoid surfaces covered by different morphological types of osteoblasts (plump, intermediate, and flat). Negative correlations were found between AlS and OblS/OS (r = −0.57, p < 0.001), intermediate OblS/OS (r = −0.38, p < 0.05) and flat OblS/OS (r = −0.56, p < 0.01). These findings indicate an impairment of osteoblastic function, with depression of bone formation at all levels, and strongly suggest a toxic effect of Al on osteoblasts.