We have assessed the bone histology in 259 chronic dialysis patients, all of whom were in the same dialysis program. All patients had bone biopsies with quantitative histomorphometry, intact parathyroid hormone (PTH) measurements, basal and deferoxamine stimulated serum aluminum levels. Results demonstrate the increased incidence of the recently described aplastic bone lesion, particularly in patients treated with peritoneal dialysis (PD). Aluminum-related bone disease is much less common than previously described, perhaps in relation to the declining use of aluminum as a phosphate binder. A different pattern of bone lesions is seen in PD as compared with hemodialysis (HD), with low turnover disorders comprising 66% of the lesions seen in PD and high turnover lesions accounting for 62% of the bone histologic findings in HD. The difference in these patterns may relate to alterations in PTH levels, as mean PTH levels in HD patients were 2-1/2 times the levels found in PD patients (P < 0.0005), while older age, higher prevalence of diabetes and a shorter duration of dialysis may also have contributed to the findings in the PD patients. We suggest that PD, perhaps by maintaining calcium at higher levels, may more effectively suppress the parathyroid gland.

No abstract

No abstract

A histochemical stain for bone aluminum allowed us to determine the prevalence and staining characteristics of aluminum in renal osteodystrophy. The staining method correlated well with the results of atomic-absorption studies in 96 samples (r = 0.81; P less than 0.001). We examined 315 bone-biopsy samples. No aluminum was seen in controls or patients with nonrenal bone disease. In renal osteodystrophy, the mean level of stainable aluminum was significantly higher in osteomalacic lesions (1.12 +/- 0.09 mm per square millimeter of tissue area) than in mild, mixed, of fibrotic lesions (0.43 +/- 0.06, 0.34 +/- 0.11, and 0.10 +/- 0.03 mm per square millimeter, respectively; P less than 0.001). Seventy per cent of osteomalacic samples had heavy aluminum staining. The bone-apposition rate, measured by double tetracycline labels, was low in 89 per cent of the samples with high levels of aluminum. The mean level of stainable bone aluminum in patients who had a clinical response to calcitriol was significantly lower than in those who did not respond (0.13 +/- 0.4 vs. 1.06 +/- 0.9 mm per square millimeter; P less than 0.01). We conclude that aluminum deposition is associated with impaired bone formation or mineralization and with a poor response to calcitriol therapy.

To evaluate the relationship between aluminum and the characteristics of bone disease in uremia, bone aluminum content and quantitative histomorphometric analysis of bone were evaluated in bone biopsies from 59 uremic patients undergoing maintenance hemodialysis. Biopsies were classified as showing 1) pure osteomalacia (OM) in 23 cases, 2) osteitis fibrosa (OF) in 13, 3) mixed in 7, and 4) mild lesions in 16. There were no significant differences in levels of serum calcium or alkaline phosphatase between the groups, but serum phosphorus levels were slightly higher in those with OF. Serum immunoreactive parathyroid hormone levels were greater in the patients with OF and mixed lesions than in patients with OM or mild lesions (P less than 0.01). Bone aluminum exceeded normal in all groups (P less than 0.01), with values of 175 +/- 18 mg/kg dry wt in OM patients, 46 +/- 7 of OF patients, 81 +/- 29 in mixed subjects, and 67 +/- 7 in patients with mild lesions. Bone aluminum was significantly higher in the OM patients than in any other group (P less than 0.01); also, bone aluminum correlated with the quantitative measure of unmineralized osteoid in OM (r = 0.67; P less than 0.001); no correlations existed for the other groups. There were inverse correlations between bone aluminum and the serum immunoreactive parathyroid hormone (r = -0.35; P less than 0.01) and resorbing surface on biopsy (r = -0.44; P less than 0.001). Bone aluminum correlated with the duration of hemodialysis in patients with OF with mixed and mild lesions (r = 0.49); no relation was seen in OM patients, and bone aluminum was higher for the duration of dialysis, suggesting that aluminum may accumulate more rapidly in OM subjects. These findings are consistent with but do not prove the hypothesis that aluminum plays a pathogenic role in dialysis osteomalacia; the mechanism by which aluminum accumulates remains unknown.