Aluminum intoxication of bone in renal failure - Fact or Fiction?

We studied prospectively in four patients on chronic maintenance dialysis the effects of administration of desferrioxamine (Desferal®), a chelator of aluminum, on the removal of aluminum from bone and on bone histology. Transient rises in serum aluminum were found after initiation of therapy for a period of 1 week to 3 months. Higher degree of bone aluminum accumulation was associated with a more persistent rise in serum aluminum. Bone biopsy specimens before therapy revealed mixed uremic osteodystrophy associated with bone aluminum accumulation in three patients, and low turnover osteomalacia in the other patient. Bone aluminum accumulation was diagnosed by energy dispersive X-ray analysis, histochemically stainable bone aluminum, and increased aluminum content in bone. After 6 to 8 months of therapy with desferrioxamine, repeat bone biopsy specimens revealed disappearance or reduction in extent of stainable bone aluminum. The differences in bone histology before and after therapy were similar to those observed between uremic patients with and without accumulation of aluminum in bone. Removal of aluminum from bone was associated with a reduction in volume of lamellar osteoid, an increase in volume of osteoid of abnormal 'woven' texture, and increased activity of bone forming and resorbing cells, as evidenced by an increase in osteoid-osteoblast interface, bone-osteoclast interface, and mineralization rate. These histologic changes were accompanied by a rise in serum parathyroid hormone levels and marked clinical improvement, such as decrease in bone and muscle pain, increased strength, and physical activity. These observations fulfill the fourth prerequisite formulated by Koch for an etiologic agent. The presented data demonstrate that aluminum is an etiologic agent for mineralization abnormalities seen in patients with renal failure.