Removal of pamidronate from bone in rats using systemic and local chelation

R. Nicole Howie, Maryka Bhattacharyya, Mohamed E. Salama, Mona El Refaey, Carlos M Isales, James Borke, Asma Daoudi, Fardous Medani, Mohammed Elsayed Elsalanty

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objectives 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. Design 32 Sprague Dawley rats were given an injection of fluorescent pamidronate (OsteoSense EX; 0.16 nmol/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.

Original languageEnglish (US)
Pages (from-to)1699-1707
Number of pages9
JournalArchives of Oral Biology
Volume60
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

pamidronate
Diphosphonates
Bone and Bones
Chelating Agents
Femur
Bone Matrix
Poisons
Feasibility Studies
Durapatite
Tibia
Cadmium
Edetic Acid
Citric Acid
Sprague Dawley Rats
Spine
Homeostasis
Fluorescence

Keywords

  • Bisphosphonates
  • Bone
  • Chelating agents
  • Feasibility study
  • Osteonecrosis of the jaw

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)
  • Cell Biology

Cite this

Removal of pamidronate from bone in rats using systemic and local chelation. / Howie, R. Nicole; Bhattacharyya, Maryka; Salama, Mohamed E.; Refaey, Mona El; Isales, Carlos M; Borke, James; Daoudi, Asma; Medani, Fardous; Elsalanty, Mohammed Elsayed.

In: Archives of Oral Biology, Vol. 60, No. 12, 01.12.2015, p. 1699-1707.

Research output: Contribution to journalArticle

Howie, RN, Bhattacharyya, M, Salama, ME, Refaey, ME, Isales, CM, Borke, J, Daoudi, A, Medani, F & Elsalanty, ME 2015, 'Removal of pamidronate from bone in rats using systemic and local chelation', Archives of Oral Biology, vol. 60, no. 12, pp. 1699-1707. https://doi.org/10.1016/j.archoralbio.2015.09.001
Howie, R. Nicole ; Bhattacharyya, Maryka ; Salama, Mohamed E. ; Refaey, Mona El ; Isales, Carlos M ; Borke, James ; Daoudi, Asma ; Medani, Fardous ; Elsalanty, Mohammed Elsayed. / Removal of pamidronate from bone in rats using systemic and local chelation. In: Archives of Oral Biology. 2015 ; Vol. 60, No. 12. pp. 1699-1707.
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abstract = "Objectives 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. Design 32 Sprague Dawley rats were given an injection of fluorescent pamidronate (OsteoSense EX; 0.16 nmol/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.",
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AU - Isales, Carlos M

AU - Borke, James

AU - Daoudi, Asma

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N2 - Objectives 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. Design 32 Sprague Dawley rats were given an injection of fluorescent pamidronate (OsteoSense EX; 0.16 nmol/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.

AB - Objectives 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. Design 32 Sprague Dawley rats were given an injection of fluorescent pamidronate (OsteoSense EX; 0.16 nmol/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.

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