title: 22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis.
abstract: 22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis.
  
  
  BACKGROUND
  22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure.
  
  
  METHODS
  Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks.
  
  
  RESULTS
  Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function.
  
  
  CONCLUSIONS
  These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.
authors.affiliation: Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirata
authors.forename: K
authors.initials: K
authors.lastname: Katsumata
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: N
authors.initials: N
authors.lastname: Koike
authors.forename: K
authors.initials: K
authors.lastname: Endo
authors.forename: K
authors.initials: K
authors.lastname: Tsunemi
authors.forename: H
authors.initials: H
authors.lastname: Ohkawa
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
authors.forename: M
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002908:Chronic Disease; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005246:Feedback / Q000502:physiology; D005355:Fibrosis; D006020:Glycopeptides; D006962:Hyperparathyroidism, Secondary / Q000150:complications; D008297:Male; D009393:Nephritis / Q000139:chemically induced / Q000150:complications*; D010000:Osteitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000150:complications; D014511:Uremia / Q000139:chemically induced / Q000150:complications
chemical_list: D000970:Antineoplastic Agents; D006020:Glycopeptides; D002117:Calcitriol; C051883:maxacalcitol