Effect of 22-oxacalcitriol on bone histology of hemodialyzed patients with severe secondary hyperparathyroidism

Abstract

To examine the effectiveness of 22-oxacalcitriol (OCT) injection on the improvement of severe osteitis fibrosa, we studied 10 hemodialyzed patients (age, 59 ± 12 years). The initial OCT dose was 5 μg and was administered three times weekly at the end of each hemodialysis session. OCT doses (1, 3, 5, 10, 15, and 20 μg) were changed in subsequent weeks to maintain serum calcium levels at less than 11.5 mg/dL. Administration of OCT significantly suppressed serum intact parathyroid hormone (PTH) from an initial level of 1,193 ± 584 to 775 ± 552 pg/mL in the 24th week (n = 10). OCT increased PTH levels again to 857 ± 635 pg/mL in the 48th week (n = 7). Among the 10 patients, 5 patients (high responders) showed more than a 50% suppression of serum intact PTH levels at the end of the study. The rest of the patients had hypercalcemia and did not receive increased OCT doses (low responders). At the start of the treatment, the only difference between high and low responders was serum calcium level. Serum calcium levels (adjusted for serum albumin level) increased from 9.7 ± 0.7 mg/dL (n = 10) at the beginning to 10.5 ± 0.6 mg/dL (n = 10) in the 24th week and to 11.1 ± 0.7 mg/dL (n = 7) in the 48th week. Six patients (1 to 6) agreed to undergo a second bone biopsy in the 24th week of OCT administration. In bone histomorphometric measurements, OCT significantly changed bone marrow fibrosis, mineralization (labeled mineralizing surface and bone formation rate), and osteoid formation (osteoid volume and thickness). In conclusion, intravenous OCT effectively suppressed PTH secretion and improved the bone histological characteristics of severe osteitis fibrosa, especially in patients with initial serum calcium levels less than 10 mg/dL. With concerns about OCT causing adynamic bone, additional bone histological data are needed to ensure the long-term safety of OCT.