Desferrioxamine therapy in hemodialysis patients with aluminum-associated bone disease

Abstract

Aluminium toxicity in dialysis patients is associated with decreased bone turnover and a relative parathyroid hormone (PTH) deficiency. Desferrioxamine (DFO), a chelating agent, has been reported to improve bone histology in aluminium associated, low turnover bone disease in dialysis patients not subjected to parathyroidectomy. Information on the effect of DFO therapy on parathyroid gland function is lacking. In the present study, in addition to changes in bone histology, parathyroid gland function was evaluated in 18 hemodialysis patients with aluminium associated, low turnover bone disease (osteomalacia and aplastic bone disease) before and after one year of DFO treatment (1 to 6 g/week). Parathyroid gland function was assessed by using a calcium free and high calcium (3.5 to 4 mEq/liter) hemodialysis bath. A comparison of findings before and after DFO treatment revealed the following: 1) no difference in serum calcium, phosphorus, alkaline phosphatase, albumin, and aluminum; 2) a decrease in stainable trabecular bone aluminum (P < 0.001), and an increase in osteoblastic osteoid (P < 0.03), osteoclasts/mm2 (P < 0.01), and bone formation rate (P < 0.008); 3) in previously parathyroidectomized patients, an increase in osteoblastic osteoid (P < 0.001); 4) a shift of the PTH-calcium curve to the right; thus, for similar levels of serum calcium, the PTH concentration was increased after DFO; 5) an increase in the PTH concentration (P < 0.02) at the serum calcium level required for maximum PTH inhibition; 6) an increase in the serum calcium level (P < 0.02) at the set point for PTH (the serum calcium concentration required to suppress PTH by 50%); and 7) no difference in maximum PTH stimulation induced by hypocalcemia. In conclusion, in patients with aluminum associated, low turnover bone disease: 1) aluminum removal from bone may improve bone histology even in patients with total parathyroidectomy; 2) aluminum accumulation may be an important factor in the PTH deficiency; and 3) DFO therapy appears to result in increased PTH secretion per individual parathyroid cell.