Efficacy of 1α-Hydroxycholesterol (1α-D₃) on the Long Term Treatment of ROD

Abstract

Effects of long term treatment of ROD by peroral administration of 1α-D₃ were evaluated. Twenty patients under stable hemodialysis having some signs of hypocalcemia, hyper-alkalinephosphatasemia, radiological bone changes or symptoms like bone fracture or bone pain were followed up about 5 years under daily administration of 1α-D₃. As a control group, 15 hemodialysed patients without clinical sign or symptom of ROD were followed up for the same period. The results obtained were as follows: 1) A dose dependent correction of hypocalcemia and hyperalkalinephosphatasemia was confirmed in all cases under 1α-D₃ treatment. However significant decrease of serum inorganic phosphate and increase of serum magnesium levels were observed only in high dose of 1α-D₃ administration, namely 3.0μg/day. 2) Serum iPTH levels (C-terminal assay) were unstable during three months of 1a-D₃ administrap tion but showed a significant decrease after 23 months. 3) Improvement of radiological bone changes estimated from MCI and from the pattern of subperiosteal bone resorption was clearly demonstrated. However to obtain significant effects on bone radiography, observation of more than three years was needed. Considering the evidence of decreasing tendency of MCI in hemodialysed patients, the early administration of 1α-D₃ might be inevitable. 4) From the evidence of a sharp increase of serum calcinum level and a high probability of hyper calcemia in its high dose administration, 1.Oμg/day in initial dose and stepwise addition of 0.5-1.0μg/day might be more safer. 5) As side effects of 1α-D₃ administration, there were liver function disturbance in 2/20, itching is 3/20 and hypercalcemia in 5/20.