1,25-(OH)2-16ene-23yne-D3 reduces secondary hyperparathyroidism in uremic rats with little calcemic effect.
OBJECTIVE
To compare the effects of vitamin D analogs versus calcitriol on serum levels of Ca, P and parathyroid hormone (PTH). A compound better than calcitriol should increase the Ca x P product less than calcitriol for an equivalent decrease in PTH levels.


METHODS
Biological activity of 4 vitamin D analogs, 1,25-(OH)(2)-16ene- D(3) (RO(1)), 1,25-(OH)(2)-16ene-23yne-D(3) (RO(2)), 1,25-(OH)(2)-26,27-hexafluoro-16ene-23yne-D(3) (RO(3)) and 1,25-(OH)(2)-16ene-23yne-26,27-hexafluoro-19nor-D(3) (RO(4)) was tested vs. calcitriol in parathyroidectomized rats. In a second set of experiments, the effects of RO(2), RO(4) and calcitriol were studied in 5/6 nephrectomized rats with secondary hyperparathyroidism.


RESULTS
In parathyroidectomized rats, all analogs (250 pmol/day) led calcemia to rise after 7 days. In uremic rats, all treatments reduced PTH levels. RO(4) revealed toxicity. RO(2) was as effective as calcitriol in suppressing PTH in a dose dependent manner. Mean plasma ionized calcium did not change from baseline to day 14 and day 28 on RO(2) (250 or 500 pmol/day) whereas it increased significantly on RO(2) (1,000 pmol/day) and calcitriol (125 or 250 pmol/day). Increasing the dose of calcitriol led Ca x P to rise more dramatically than increasing the dose of RO(2), which appears to have a wider therapeutic window than calcitriol.


CONCLUSIONS
1,25-(OH)(2)-16ene-23yne-D(3) (RO(2)) may represent a novel candidate for the treatment of renal osteodystrophy in humans.
Lippuner
Kurt
K
Osteoporosis Unit/Policlinic of Medicine, University Hospital of Berne, Berne, Switzerland.
Perrelet
Romain
R
Casez
Jean-Paul
JP
Popp
Albrecht
A
Uskokovic
Milan R
MR
Jaeger
Philippe
P
D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives*; D002118:Calcium / Q000097:blood; D006934:Hypercalcemia / Q000097:blood / Q000139:chemically induced; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D007274:Injections, Intraperitoneal; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D016226:Phosphorus, Dietary / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000097:blood / Q000150:complications*
D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary; D010758:Phosphorus; D002117:Calcitriol; C064183:Ro 23-7553; D002118:Calcium