Bisphosphonate binding affinity affects drug distribution in both intracortical and trabecular bone of rabbits

John Turek, F. Hal Ebetino, Mark W. Lundy, Shuting Sun, Boris A. Kashemirov, Charles E. McKenna, Maxime A. Gallant, Lilian I. Plotkin, Teresita Bellido, Xuchen Duan, James T. Triffitt, R. Graham G. Russell, David B. Burr, Matthew R. Allen

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Differences in the binding affinities of bis-phosphonates for bone mineral have been proposed to determine their localizations and duration of action within bone. The main objective of this study was to test the hypothesis that mineral binding affinity affects bis-phosphonate distribution at the basic multicellular unit (BMU) level within both cortical and cancellous bone. To accomplish this objective, skeletally mature female rabbits (n = 8) were injected simultaneously with both low- and high-affinity bisphosphonate analogs bound to different fluorophores. Skeletal distribution was assessed in the rib, tibia, and vertebra using confocal microscopy. The staining intensity ratio between osteocytes contained within the cement line of newly formed rib osteons or within the reversal line of hemiosteons in vertebral trabeculae compared to osteocytes outside the cement/reversal line was greater for the high-affinity compared to the low-affinity compound. This indicates that the low-affinity compound distributes more equally across the cement/reversal line compared to a high-affinity compound, which concentrates mostly near surfaces. These data, from an animal model that undergoes intracortical remodeling similar to humans, demonstrate that the affinity of bisphosphonates for the bone determines the reach of the drugs in both cortical and cancellous bone.

Original languageEnglish (US)
Pages (from-to)202-210
Number of pages9
JournalCalcified Tissue International
Volume90
Issue number3
DOIs
StatePublished - Jan 16 2012

Keywords

  • Anti-remodeling
  • Drug accumulation
  • Fluorescent bisphosphonate
  • Skeletal distribution

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Turek, J., Ebetino, F. H., Lundy, M. W., Sun, S., Kashemirov, B. A., McKenna, C. E., Gallant, M. A., Plotkin, L. I., Bellido, T., Duan, X., Triffitt, J. T., Russell, R. G. G., Burr, D. B., & Allen, M. R. (2012). Bisphosphonate binding affinity affects drug distribution in both intracortical and trabecular bone of rabbits. Calcified Tissue International, 90(3), 202-210. https://doi.org/10.1007/s00223-012-9570-0