title: Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH.
  
  
  METHODS
  Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality).
  
  
  RESULTS
  PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties.
  
  
  CONCLUSIONS
  These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.
authors.affiliation: Materials Engineering, Purdue University, Weldon School of Biomedical Engineering, Purdue University, West Lafayatte, Ind., USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Newman
authors.forename: Nannan
authors.initials: N
authors.lastname: Tian
authors.forename: Max A
authors.initials: MA
authors.lastname: Hammond
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wallace
authors.forename: Drew M
authors.initials: DM
authors.lastname: Brown
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Allen
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002117:Calcitriol / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D004195:Disease Models, Animal; D050723:Fractures, Bone / Q000517:prevention & control; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000097:blood; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*
chemical_list: D002120:Calcium Channel Agonists; D010281:Parathyroid Hormone; D002117:Calcitriol