This study represents the first randomized prospective, double-blind, placebo-controlled
trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients
with mild to moderate renal failure. Sixteen patients with chronic renal impairment
(creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose
of 0.25 to 0.5 microgram daily (eight patients), or placebo. Transiliac crest bone
biopsies were performed before entrance into the study and after 12 months of experimental
observation. None of the patients were symptomatic or had radiological evidence of
bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D
levels were low in seven patients and parathyroid hormone levels were elevated in
seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment
was associated with a significant fall in serum phosphorus and alkaline phosphatase
concentrations as well as with histological evidence of an amelioration of hyperparathyroid
changes. In contrast to previous reports, no deterioration of renal function attributable
to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed
combined with meticulous monitoring. Further investigation is required to determine
whether alternative therapeutic strategies (smaller doses or intermittent therapy)
may avoid the potential for suppressing bone turnover to abnormally low levels in
the long term.