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

Calcif Tissue Int. 2012 Mar;90(3):202-10. doi: 10.1007/s00223-012-9570-0. Epub 2012 Jan 17.


Differences in the binding affinities of bisphosphonates 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 bisphosphonate 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Bone Density Conservation Agents / pharmacokinetics*
  • Bone Remodeling / drug effects*
  • Bone Remodeling / physiology
  • Bone and Bones / cytology
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism*
  • Diphosphonates / pharmacokinetics*
  • Female
  • Haversian System / cytology
  • Haversian System / drug effects
  • Haversian System / metabolism
  • Osteocytes / cytology
  • Osteocytes / drug effects
  • Osteocytes / metabolism
  • Osteoporosis / drug therapy
  • Rabbits
  • Tissue Distribution / physiology


  • Bone Density Conservation Agents
  • Diphosphonates