title: Combination of early bisphosphonate administration and irradiation leads to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model.
abstract: BACKGROUND
  The goal of the current study was to analyze the combined effect of bisphosphonates (BPs) and irradiation on remineralization and restabilization of osteolytic bone metastases in an animal tumor model.
  
  
  METHODS
  Bone metastases were induced in male Wistar rats via intraosseous injection of the Walker carcinosarcoma 256B cell line into both proximal tibia metaphyses on Day 1 of the study. Three treatment groups were analyzed. All animals received a single radiation dose of 17 grays (in the form of 6-megaelectron-volt electrons) on Day 7 and were sacrificed on Day 49. Group 1 (the control group) was treated with irradiation only. Groups 2 and 3 received additional BPs (clodronate; daily intraperitoneal injection dose, 20 mg/kg per day). In Group 2, BPs were given before irradiation, on Days 3-6; this schedule later was referred to as early BP treatment. In Group 3, BPs were administered simultaneously with irradiation, on Days 7-10; this schedule later was referred to as simultaneous BP treatment. The endpoints of the study were bone density and microstructural parameters of bone on Day 49. Bone density was measured using X-ray absorption. Microstructural parameters of bone were assessed using histomorphometry. A total of thirty tibiae were analyzed in each group.
  
  
  RESULTS
  After irradiation, bone density was significantly higher among animals in the early BP treatment group compared with those in the control group and those in the simultaneous BP treatment group (P = 0.001). Histomorphometric analysis of bone showed significantly better-preserved (P < 0.001) microstructural parameters (bone area, trabecular number, and trabecular separation) in the early BP treatment group compared with the control and simultaneous BP treatment groups.
  
  
  CONCLUSIONS
  Early BP administration in combination with irradiation led to improved remineralization and restabilization of osteolytic bone metastases in an animal tumor model.
authors.affiliation: Department of Clinical Radiology, University of Heidelberg, Heidelberg, Germany. krempien@med.uni-heidelberg.de
authors.forename: Robert
authors.initials: R
authors.lastname: Krempien
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Harms
authors.forename: Martina
authors.initials: M
authors.lastname: Treiber
authors.forename: Michael
authors.initials: M
authors.lastname: Wannenmacher
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Krempien
mesh_terms: D000818:Animals; D015519:Bone Density; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D002113:Calcification, Physiologic / Q000502:physiology*; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D008297:Male; D010014:Osteolysis / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004164:Diphosphonates