title: Effects of zoledronate on the radiation-induced collagen breakdown: a prospective randomized clinical trial.
abstract: BACKGROUND
  A negative side effect of therapeutic irradiation is the radiation-induced bone loss which can lead, in long term, to pathological fractures. Until today, the detailed mechanism is unknown. If osteoclasts would mainly contribute to the pathological bone loss, bisphosphonates could potentially counteract the osteolytic process and possibly help to prevent long-term complications. The aim of this study was to evaluate the effect of zoledronic acid on the early radiation-induced degradation of bone collagen fibrils by monitoring the urinary excretion of hydroxylysylpyridinoline and lysylpyridinoline under radiotherapy.
  
  
  METHODS
  A total of 40 patients with skeletal metastases were assigned for a local radiotherapy and bisphosphonate treatment. The patients were prospectively randomized into two treatment groups: group A (n = 20) received the first zoledronate administration after and group B (n = 20) prior to the radiotherapy. Urine samples were collected from each patient on the first day, in the middle, and on the last day of the radiation therapy. Measurement of the bone metabolites hydroxylysylpyridinoline and lysylpyridinoline was performed by high-performance liquid chromatography. Statistical analysis was performed using the Mann-Whitney U test.
  
  
  RESULTS
  The hydroxylysylpyridinoline and lysylpyridinoline excretion decreased significantly in the combined bisphosphonate and radiotherapy group (p = 0.02, p = 0.08). No significant change of the hydroxylysylpyridinoline and lysylpyridinoline excretion was determined in the patients that received solely irradiation.
  
  
  CONCLUSIONS
  The results indicate the ability of zoledronate to prevent the early radiation-induced bone collagen degradation suggesting that the radiation-induced bone loss is mainly caused by osteoclastic bone resorption rather than by a direct radiation-induced damage.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, Haus 26, 24105, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gierloff
authors.forename: M
authors.initials: M
authors.lastname: Reutemann
authors.forename: A
authors.initials: A
authors.lastname: Gülses
authors.forename: P
authors.initials: P
authors.lastname: Niehoff
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Y
authors.initials: Y
authors.lastname: Açil
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000652:urine; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D001842:Bone and Bones / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D024042:Collagen Type I / Q000187:drug effects* / Q000528:radiation effects; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000517:prevention & control; D011878:Radiotherapy / Q000009:adverse effects; D000077211:Zoledronic Acid
chemical_list: D000596:Amino Acids; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; C015484:pyridinoline; D000077211:Zoledronic Acid; C036020:deoxypyridinoline