title: Effects of zoledronate on irradiated bone in vivo: analysis of the collagen types I, V and their cross-links lysylpyridinoline, hydroxylysylpyridinoline and hydroxyproline.
abstract: Radiotherapy can lead to a reduction of bone density with an increased risk of pathological fractures. Bisphosphonates may represent a preventive treatment option by increasing the density of anorganic bone mineral. Yet it is unknown how bisphosphonates act on irradiated collagen cross-links, which play an essential role for the mechanical stability of bone. The aim of this study was to evaluate the effects of zoledronate on bone collagens and their cross-links after irradiation. The right femur of 37 rats was irradiated with a single dose of 9.5 Gy at a high dose rate using an afterloading machine. Half of the rats (n=18) received additionally a single dose zoledronate (0.1 mg/kg body weight). Fourteen and 100 days after irradiation the femora were collected for histologic evaluation and determination of the collagen cross-links lysylpyridinoline, hydroxylysylpyridinoline, and hydroxyproline. The collagen types were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Fourteen days after treatment the lysylpyridinoline levels of all treatment groups were significantly lower compared to the untreated control. After 100 days, in the combined radiotherapy+zoledronate group significantly lower lysylpyridinoline values were determined (p=0.009). Radiotherapy and/or zoledronate did not change significantly the level of hydroxylysylpyridinoline. The concentration of hydroxyproline was 14 days after irradiation significantly higher in the combined treatment group compared to the control. No significant differences were observed 100 days after treatment. Zoledronate does not have the ability to restore the physiological bone collagen cross-link levels after radiotherapy. However, this would be necessary for regaining the physiological mechanical stability of bone after irradiation and therefore to prevent effectively radiation-induced fractures.
authors.affiliation: Department of Oral and Maxillofacial Surgery, UK-SH, Campus Kiel, Germany.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Açil
authors.forename: Matthias
authors.initials: M
authors.lastname: Gierloff
authors.forename: Carolin
authors.initials: C
authors.lastname: Behrens
authors.forename: Björn
authors.initials: B
authors.lastname: Möller
authors.forename: Volker
authors.initials: V
authors.lastname: Gassling
authors.forename: Peter
authors.initials: P
authors.lastname: Niehoff
authors.forename: Jörg
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Maciej
authors.initials: M
authors.lastname: Simon
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D024042:Collagen Type I / Q000032:analysis / Q000187:drug effects* / Q000528:radiation effects; D024062:Collagen Type V / Q000032:analysis / Q000187:drug effects* / Q000528:radiation effects; D004164:Diphosphonates / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006909:Hydroxyproline / Q000187:drug effects / Q000528:radiation effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077211:Zoledronic Acid
chemical_list: D000596:Amino Acids; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D024062:Collagen Type V; D004164:Diphosphonates; D007093:Imidazoles; C015484:pyridinoline; D000077211:Zoledronic Acid; C036020:deoxypyridinoline; D006909:Hydroxyproline