title: Removal of pamidronate from bone in rats using systemic and local chelation.
abstract: OBJECTIVE
  Bisphosphonates become adsorbed on hydroxyapatite crystals in the bone matrix. In case of side-effects, stopping the treatment would not affect the bisphosphonates already deposited in bone. This study tests the feasibility of in-vivo targeted removal of bisphosphonates from bone using chelating agents.
  
  
  METHODS
  32 Sprague Dawley rats were given an injection of fluorescent pamidronate (OsteoSense EX; 0.16nmol/g). They were treated with either systemic (cadmium) or local [ethylenediaminetetraacetic (EDTA) or citric acid (CA)] chelating agents to induce the removal of the bisphosphonate from bone. We evaluated the decrease in fluorescence in the alveolar bone, femur, tibia, and vertebrae. We also analyzed the systemic effects of treatment.
  
  
  RESULTS
  Systemic chelation reduced the pamidronate signal universally. However, the maximum reduction was observed in the alveolar bone and femur (22% and 21%, p values 0.008 and 0.028, respectively). Systemic chelation did not impair calcium homeostasis. The chelation effect was not due to a systemic toxic effect on the liver or kidney. On the other hand local chelation at the extraction site significantly (p=0.011) decreased the pamidronate signal at bony surfaces of the socket.
  
  
  CONCLUSIONS
  Systemic and local chelating agents can remove bisphosphonate from bone. This study establishes a new concept for the prevention of side effects of bisphosphonates during high-risk situations.
authors.affiliation: Georgia Regents University, Augusta, GA, USA.
authors.forename: R Nicole
authors.initials: RN
authors.lastname: Howie
authors.affiliation: Georgia Regents University, Augusta, GA, USA.
authors.forename: Maryka
authors.initials: M
authors.lastname: Bhattacharyya
authors.affiliation: University of Utah, Salt Lake City, UT, USA.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salama
authors.affiliation: Georgia Regents University, Augusta, GA, USA.
authors.forename: Mona El
authors.initials: ME
authors.lastname: Refaey
authors.affiliation: Georgia Regents University, Augusta, GA, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Isales
authors.affiliation: Western University of Health Sciences, Pomona, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Borke
authors.affiliation: Georgia Regents University, Augusta, GA, USA.
authors.forename: Asma
authors.initials: A
authors.lastname: Daoudi
authors.affiliation: Georgia Regents University, Augusta, GA, USA.
authors.forename: Fardous
authors.initials: F
authors.lastname: Medani
authors.affiliation: Georgia Regents University, Augusta, GA, USA. Electronic address: melsalanty@gru.edu.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Elsalanty
mesh_terms: D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism*; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D019343:Citric Acid / Q000494:pharmacology; D004164:Diphosphonates / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005240:Feasibility Studies; D007677:Kidney Function Tests; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002614:Chelating Agents; D004164:Diphosphonates; D010281:Parathyroid Hormone; D002104:Cadmium; D019343:Citric Acid; D004492:Edetic Acid; D000077268:Pamidronate; D002118:Calcium
keywords: Bisphosphonates; Bone; Chelating agents; Feasibility study; Osteonecrosis of the jaw