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 language | English (US) |
|---|---|
| Pages (from-to) | 1699-1707 |
| Number of pages | 9 |
| Journal | Archives of Oral Biology |
| Volume | 60 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2015 |
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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 journal › Article
}
TY - JOUR
T1 - Removal of pamidronate from bone in rats using systemic and local chelation
AU - Howie, R. Nicole
AU - Bhattacharyya, Maryka
AU - Salama, Mohamed E.
AU - Refaey, Mona El
AU - Isales, Carlos M
AU - Borke, James
AU - Daoudi, Asma
AU - Medani, Fardous
AU - Elsalanty, Mohammed Elsayed
PY - 2015/12/1
Y1 - 2015/12/1
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.
KW - Bisphosphonates
KW - Bone
KW - Chelating agents
KW - Feasibility study
KW - Osteonecrosis of the jaw
UR - http://www.scopus.com/inward/record.url?scp=84942879742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942879742&partnerID=8YFLogxK
U2 - 10.1016/j.archoralbio.2015.09.001
DO - 10.1016/j.archoralbio.2015.09.001
M3 - Article
VL - 60
SP - 1699
EP - 1707
JO - Archives of Oral Biology
JF - Archives of Oral Biology
SN - 0003-9969
IS - 12
ER -