title: The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling.
abstract: BACKGROUND
  Loss of bone mass after transplantation begins in the early periods after transplantations and may persist for several years, even in patients with normal renal function. While the pathogenesis of these abnormalities is still unclear, several studies suggest that preexisting bone disease, glucocorticoid therapy, and alterations in phosphate metabolism may play important roles. Recent studies indicate that osteoblast apoptosis and impaired osteoblastogenesis play important roles in the pathogenesis of glucocorticoid-induced osteoporosis.
  
  
  OBJECTIVE
  To examine the early alterations in osteoblast number and surfaces during the period following renal transplantation.
  
  
  METHODS
  Twenty patients with a mean age of 36.5 +/- 12 years were subjected to bone biopsy 22 to 160 days after renal transplantation. In 12 patients, a control biopsy was performed on the day of transplantation. Bone sections were evaluated by histomorphometric analysis and cell DNA fragmentation by the methods of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL), using immunoperoxidase and direct immunofluorescence techniques.
  
  
  RESULTS
  The main alterations in posttransplant biopsies were a decrease in osteoid and osteoblast surfaces, adjusted bone formation rate, and prolonged mineralization lag time. Peritrabecular fibrosis was markedly decreased. None of the pretransplant biopsies revealed osteoblast apoptosis. In contrast, TUNEL-positive cells in the proximity of osteoid seams or in the medullary space were observed in nine posttransplant biopsies of which four had mixed bone disease, two had adynamic bone disease, one had osteomalacia, one had osteitis fibrosa, and one had mild hyperparathyroid bone disease. Osteoblast number in posttransplant biopsies with apoptosis was lower as compared with posttransplant biopsies without apoptosis. In addition, most of them showed a marked shift toward quiescence from the cuboidal morphology of active osteoblasts. Serum phosphorus levels were lower in patients showing osteoblast apoptosis and correlated positively with osteoblast number and negatively with the number of apoptotic osteoblasts. In addition, posttransplant osteoblast surface correlated positively with parathyroid hormone (PTH) levels and negatively with glucocorticoid cumulative dose.
  
  
  CONCLUSIONS
  The data suggest that impaired osteoblastogenesis and early osteoblast apoptosis may play important roles in the pathogenesis of posttransplant osteoporosis. The possible mechanisms involved in the pathogenesis of theses alterations include posttransplant hypophosphatemia, the use of glucocorticoids, and the preexisting bone disease. PTH seems to have a protective effect by preserving osteoblast survival.
authors.affiliation: Centro Nacional de Diálisis y Trasplante, Division of Nephrology, Hospital Universitario de Caracas, Venezuela.
authors.forename: Eudocia
authors.initials: E
authors.lastname: Rojas
authors.forename: Raul G
authors.initials: RG
authors.lastname: Carlini
authors.forename: Paul
authors.initials: P
authors.lastname: Clesca
authors.forename: Anabella
authors.initials: A
authors.lastname: Arminio
authors.forename: Orlando
authors.initials: O
authors.lastname: Suniaga
authors.forename: Karen
authors.initials: K
authors.lastname: De Elguezabal
authors.forename: José R
authors.initials: JR
authors.lastname: Weisinger
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Bellorin-Font
mesh_terms: D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology* / Q000473:pathology*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011183:Postoperative Complications
chemical_list: D005938:Glucocorticoids; D010281:Parathyroid Hormone; D010758:Phosphorus