Local bioavailability and distribution of systemically (parenterally) administered ibandronate in the infarcted femoral head

Harry K W Kim, Mike Sanders, Sanjay Athavale, Haikuo Bian, Frieder Bauss

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Recent studies show that bisphosphonates can decrease the development of femoral head deformity following ischemic osteonecrosis by inhibiting osteoclast-mediated bone resorption. Given the potential new indication, improved understanding of pharmacokinetics of bisphosphonates as it applies to the infarcted head would be beneficial. The purpose of this study was to investigate the local bioavailability and the distribution of ibandronate in the infarcted head at the avascular and vascular phases of the disease process. Ischemic osteonecrosis of the femoral head was surgically induced in 15 piglets. One, 3, and 6 weeks following the induction of ischemia, which represent various stages of revascularization and repair, 14C-labeled ibandronate was administered intravenously. Twenty-four hours following 14C-drug administration, the level of radioactivity and its distribution in the infarcted heads were determined using liquid scintillation analysis and autoradiography. A significant correlation was found between the extent of revascularization and the level of radioactivity measured in the infarcted heads (r = 0.80, P < 0.05). The radioactivity level in the infarcted heads measured by liquid scintillation was similar to the negative controls at 1 week when revascularization was absent, but it increased significantly at 6 weeks when extensive revascularization was present (P ≤ 0.00004). Autoradiographic assessment showed similar silver grain counts in the infarcted heads compared to the background at 1 week. At 3 weeks, a significant increase in the silver grain count was observed in the necrotic regions of the infarcted heads compared to the background (P = 0.001) even though only a small area of the heads (2%) was found to be revascularized, suggesting diffusion of 14C-drug from the revascularized to the non-revascularized areas of the head. At 6 weeks, extensive 14C-drug binding was observed in the areas of revascularization with preferential binding of 14C-drug to the newly formed bone compared to the remaining necrotic bone (P = 0.000001). These results indicate that revascularization and repair produce significant alteration of local bioavailability and distribution of ibandronate in the infarcted head. To our knowledge, this is the first study to examine the local bioavailability and distribution of bisphosphonate in the infarcted head. Current findings have important implications with regard to the timing and dosing of bisphosphonate after the onset of ischemic osteonecrosis.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalBone
Volume39
Issue number1
DOIs
StatePublished - Jul 2006

Fingerprint

Thigh
Biological Availability
Head
Diphosphonates
Osteonecrosis
Radioactivity
Silver
Pharmaceutical Preparations
ibandronic acid
Bone and Bones
Osteoclasts
Bone Resorption
Autoradiography
Vascular Diseases
Ischemia
Pharmacokinetics

Keywords

  • Avascular necrosis
  • Bioavailability
  • Bisphosphonate
  • Femoral head
  • Ibandronate
  • Ischemic necrosis
  • Osteonecrosis

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Local bioavailability and distribution of systemically (parenterally) administered ibandronate in the infarcted femoral head. / Kim, Harry K W; Sanders, Mike; Athavale, Sanjay; Bian, Haikuo; Bauss, Frieder.

In: Bone, Vol. 39, No. 1, 07.2006, p. 205-212.

Research output: Contribution to journalArticle

Kim, Harry K W ; Sanders, Mike ; Athavale, Sanjay ; Bian, Haikuo ; Bauss, Frieder. / Local bioavailability and distribution of systemically (parenterally) administered ibandronate in the infarcted femoral head. In: Bone. 2006 ; Vol. 39, No. 1. pp. 205-212.
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abstract = "Recent studies show that bisphosphonates can decrease the development of femoral head deformity following ischemic osteonecrosis by inhibiting osteoclast-mediated bone resorption. Given the potential new indication, improved understanding of pharmacokinetics of bisphosphonates as it applies to the infarcted head would be beneficial. The purpose of this study was to investigate the local bioavailability and the distribution of ibandronate in the infarcted head at the avascular and vascular phases of the disease process. Ischemic osteonecrosis of the femoral head was surgically induced in 15 piglets. One, 3, and 6 weeks following the induction of ischemia, which represent various stages of revascularization and repair, 14C-labeled ibandronate was administered intravenously. Twenty-four hours following 14C-drug administration, the level of radioactivity and its distribution in the infarcted heads were determined using liquid scintillation analysis and autoradiography. A significant correlation was found between the extent of revascularization and the level of radioactivity measured in the infarcted heads (r = 0.80, P < 0.05). The radioactivity level in the infarcted heads measured by liquid scintillation was similar to the negative controls at 1 week when revascularization was absent, but it increased significantly at 6 weeks when extensive revascularization was present (P ≤ 0.00004). Autoradiographic assessment showed similar silver grain counts in the infarcted heads compared to the background at 1 week. At 3 weeks, a significant increase in the silver grain count was observed in the necrotic regions of the infarcted heads compared to the background (P = 0.001) even though only a small area of the heads (2{\%}) was found to be revascularized, suggesting diffusion of 14C-drug from the revascularized to the non-revascularized areas of the head. At 6 weeks, extensive 14C-drug binding was observed in the areas of revascularization with preferential binding of 14C-drug to the newly formed bone compared to the remaining necrotic bone (P = 0.000001). These results indicate that revascularization and repair produce significant alteration of local bioavailability and distribution of ibandronate in the infarcted head. To our knowledge, this is the first study to examine the local bioavailability and distribution of bisphosphonate in the infarcted head. Current findings have important implications with regard to the timing and dosing of bisphosphonate after the onset of ischemic osteonecrosis.",
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