Calcified Tissue International

, Volume 92, Issue 3, pp 251–260

Effects of Zoledronate on Irradiated Bone In Vivo: Analysis of the Collagen Types I, V and Their Cross-links Lysylpyridinoline, Hydroxylysylpyridinoline and Hydroxyproline


  • Yahya Açil
    • Department of Oral and Maxillofacial SurgeryUK-SH
    • Department of Oral and Maxillofacial SurgeryUK-SH
  • Carolin Behrens
    • Department of Oral and Maxillofacial SurgeryUK-SH
  • Björn Möller
    • Department of Oral and Maxillofacial SurgeryUK-SH
  • Volker Gassling
    • Department of Oral and Maxillofacial SurgeryUK-SH
  • Peter Niehoff
    • Department of Radiotherapy (Radiooncology)UK S-H
  • Jörg Wiltfang
    • Department of Oral and Maxillofacial SurgeryUK-SH
  • Maciej Simon
    • Department of Oral and Maxillofacial SurgeryUK-SH
Original Research

DOI: 10.1007/s00223-012-9676-4

Cite this article as:
Açil, Y., Gierloff, M., Behrens, C. et al. Calcif Tissue Int (2013) 92: 251. doi:10.1007/s00223-012-9676-4


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.


BisphosphonateBoneCollagenCollagen cross-linksRadiation-induced bone lossRadiotherapy

Copyright information

© Springer Science+Business Media New York 2012