title: Differential effects of oral doxercalciferol (Hectorol) or paricalcitol (Zemplar) in the Cyp27b1-null mouse model of uremia.
abstract: OBJECTIVE
  Kidney disease patients experience declining calcitriol levels and develop secondary hyperparathyroidism (SHPT). Animal models of uremia based on 5/6 nephrectomy (NTX) do not consistently reproduce this calcitriol deficiency. We developed an animal model, the NTX Cyp27b1-null mouse, which completely lacks endogenous calcitriol, and examined the suitability of this model for evaluation of treatment with vitamin D analogs in uremia.
  
  
  METHODS
  NTX was performed at 2 months of age. One week post-NTX, animals were treated for 4 weeks with vehicle; doxercalciferol at 30, 100 or 300 pg/g body weight (b.w.); or paricalcitol at 100, 300 or 1,000 pg/g b.w. by gavage 3 times per week.
  
  
  RESULTS
  Serum blood urea nitrogen and creatinine were elevated. Vehicle-treated NTX null mice had hypocalcemia and SHPT. Doxercalciferol at 100 or 300 pg/g b.w. normalized serum calcium and parathyroid hormone (PTH) levels. Paricalcitol at 300 or 1,000 pg/g normalized serum calcium, but PTH levels remained elevated. Osteomalacia was corrected by 100 pg/g b.w. of doxercalciferol or 1,000 pg/g b.w. of paricalcitol. The highest dose of doxercalciferol, but not of paricalcitol, significantly reduced osteitis fibrosa.
  
  
  CONCLUSIONS
  Our results reveal the differential efficacy of doxercalciferol and paricalcitol in this novel animal model incorporating both calcitriol deficiency and renal insufficiency.
authors.affiliation: Genetics Unit, Shriners Hospital for Children, Montreal, Qué., Canada.
authors.forename: René
authors.initials: R
authors.lastname: St-Arnaud
authors.forename: Alice
authors.initials: A
authors.lastname: Arabian
authors.forename: Omar
authors.initials: O
authors.lastname: Akhouayri
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Knutson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Strugnell
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency* / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D002117:Calcitriol / Q000172:deficiency / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D010000:Osteitis / Q000188:drug therapy / Q000473:pathology; D010018:Osteomalacia / Q000188:drug therapy / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D014511:Uremia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*
chemical_list: D004872:Ergocalciferols; D010281:Parathyroid Hormone; C042533:1 alpha-hydroxyergocalciferol; C084656:paricalcitol; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002118:Calcium