Adynamic bone disease, characterized by a low bone formation rate with normal or reduced amount of unmineralized osteoid, is supposed to be the consequence of aluminum intoxication in uremic patients. However, the emergence of adynamic bone disease has been recently reported in hemodialyzed patients in the total absence of aluminum overload. This study was aimed to assess whether such a histological pattern of adynamic bone disease was already present in uremic patients not yet on dialysis. Twenty-seven asymptomatic uremic patients (mean age +/- SD 43 +/- 10 years, mean creatinine clearance 19 +/- 3 ml/mm) were studied and bone biopsies were repeated in 16 of them after 18 +/- 10 months of treatment with oral calcium carbonate (1-3 g of elemental calcium/day) and calcidiol (21 +/- 14 micrograms/day). None of the patients received aluminum hydroxide, and the search for bone aluminum deposits was negative in all patients both before and after treatment. Two patients fulfilled the criteria of adynamic bone disease on their post-treatment biopsies. They originated from patients classified as having normal bone histology before treatment. Comparison with the other patients showed that they had comparable plasma C-terminal PTH but higher plasma creatinine than patients with normal bone histology and lower plasma C-terminal PTH than patients with osteitis fibrosa but comparable plasma creatinine. The plasma levels of 1,25(OH)2D reached values above normal after treatment in these two patients. It is suggested that adynamic bone disease not related to aluminum intoxication can develop in uremic patients independently of dialysis, and is favored by a relative hypoparathyroidism for the degree of renal failure, possibly induced by elevated plasma concentrations of calcitriol.