Evidence for Alterations of Vitamin D Metabolism in Methylprednisolone-Treated Rabbits

Summary

Our aim was to investigate the effects of high doses of glucocorticoids on vitamin D metabolism and to evaluate whether these effects play a role in the onset of corticosteroid-induced osteopenia. For that reason, plasma 25 hydroxyvitamin D [25(OH)D] levels and ⁴⁵Ca bone uptake were measured in 18 rabbits (group I): Eleven were treated with methylprednisolone (MPT) for 3 weeks and the results were compared to those obtained in 7 controls (C). An additional group of 15 rabbits (group II = 7 MPT and 8 C) received intraperitoneal injections of both ¹⁴C-vitamin D and ³H-25 (OH)D and plasma concentrations of labelled vitamin D, 25 hydroxyvitamin D [25(OH)D], 24,25 dihydroxyvitamin D [24,25(OH)₂D] and 1,25-dihydroxyvitamin D [1,25(OH)₂ D] were respectively measured 2 and 6 days after ¹⁴C-vitamin D and ³H-25(OH)D injections. In group I, serum calcium remained unchanged both in MPT and C animals. Plasma 25(OH)D decreased significantly (P< 0.02) in MPT rabbits compared with controls. The bone trabecular volume was correlated positively with the changes in plasma 25(OH)D: r = 0.75, P< 0.01. The results observed in group II showed that less ³H-25(OH)D remained in circulation in MPT rabbits compared with controls after a ³H-25(OH)D injection. The present results seem to indicate that the turnover rate of the 25(OH)D is accelerated in MPT animals. This alteration might be due to a disruption of the enterohepatic circulation, since both the ³H-24,25(OH)₂ D: ³H-25(OH)D ratio remained unaffected by methylprednisolone and labelled 1,25(OH)₂ D were not detectable in plasma of treated animals. However, it seems highly unlikely that the marginal alteration of the 25(OH)D metabolism could explain the profound changes in bone metabolism observed in the present study.

Key-Words:

Corticosteroid Treatment - Osteopenia - Vitamin D Metabolism