Sixteen studies that were reported in full publications and five reported as abstracts were included. The full publications comprised 10 RCTs (190 patients) and 6 non-randomised CCTs (257 patients). The abstracts related to 1 RCT (27 patients) and 4 CCTs (60 patients).
The studies were generally small and only two had more than 25 patients per treatment arm. Only one study, published in abstract format, lasted 52 weeks; the majority of the studies lasted for 16 weeks or less. Some studies used non-equivalent oral and i.v. dosing regimens: 19 studies used oral doses that were less than half as active, therapeutically, than the i.v. treatment for comparison. The included studies differed markedly in the criterion used to define hypercalcaemia.
Twelve studies published in full used calcitriol, three full publications were of alpha-calcidol and one full publication was of doxercalciferol. All the abstracts were of calcitriol.
Five studies (and two abstracts) showed that i.v. administration significantly reduced the time to PTH suppression and/or suppressed PTH to a greater extent than oral administration. Two of the five full publication studies (and one abstract) used a much greater i.v. than oral dose.
Side-effects were only reported in detail in 9 studies.
Hypercalcaemia (9 studies): the results for hypercalcaemia differed among the studies. The event rate for hypercalcaemia varied from 0.15 to 13 events per patient-year. Six studies found no significant difference between oral and i.v. dosing. Two studies found that oral treatment significantly increased hypercalcaemia, while one study found that i.v. treatment significantly increased hypercalcaemia. One larger crossover study (70 patients) that used therapeutically equivalent (defined as the dose required to produce equal reductions in PTH) found that oral doxercalciferol significantly increased hypercalcaemia (greater than 11.2 mg/dL) compared with i.v. dosing (1.6 compared with 0.5 events per patient-year, P<0.001); two other studies found similar results. The largest parallel-group study (151 patients) found that i.v. dosing increased hypercalcaemia, but the i.v. dose used was higher than the oral dose.
Hyperphosphataemia (3 studies): none of the studies found any significant difference between oral and i.v. dosing.