Retention, distribution, and effects of intraosseously administered ibandronate in the infarcted femoral head.
The local distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted femoral heads were studied. Intraosseous administration effectively delivered and distributed ibandronate in the infarcted femoral heads and decreased the femoral head deformity in a large animal model of Legg-Calve-Perthes disease.


BACKGROUND
Bisphosphonate therapy has gained significant attention for the treatment of ischemic osteonecrosis of the femoral head (IOFH) because of its ability to inhibit osteoclastic bone resorption, which has been shown to contribute to the pathogenesis of femoral head deformity. Because IOFH is a localized condition, there is a need to explore the therapeutic potential of local, intraosseous administration of bisphosphonate to prevent the femoral head deformity. The purpose of this study was to investigate the distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted head.


METHODS
IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject (14)C-labeled or unlabeled ibandronate directly into the infarcted head. (14)C-ibandronate injected heads were assessed after 48 h, 3 weeks, or 7 weeks later to determine the distribution and retention of the drug using autoradiography and liquid scintillation analysis. Femoral heads injected with unlabeled ibandronate were assessed at 7 weeks to determine the degree of deformity using radiography and histomorphometry.


RESULTS
Autoradiography showed that (14)C-Ibandronate was widely distributed in three of the four heads examined at 48 h after the injection. Liquid scintillation analysis showed that most of the drug was retained in the injected head, and almost negligible amount of radioactivity was present in the bone and organs elsewhere at 48 h. At 3 and 7 weeks, 50% and 30% of the (14)C-drug were found to be retained in the infarcted heads, respectively. Radiographic and histomorphometric assessments showed significantly better preservation of the infarcted heads treated with intraosseous administration of ibandronate compared with saline (p < 0.001).


CONCLUSIONS
This study provides for the first time the evidence that local intraosseous administration is an effective route to deliver and distribute ibandronate in the infarcted femoral head to preserve the femoral head structure after ischemic osteonecrosis. In a localized ischemic condition such as IOFH, local administration of bisphosphonate may be preferable to oral or systemic administration because it minimizes the distribution of the drug to the rest of the skeleton and bypasses the need for having a restored blood flow to the infarcted head for the delivery of the drug.
Aya-ay
James
J
Shriners Hospitals for Children, Tampa, Florida 33612, USA.
Athavale
Sanjay
S
Morgan-Bagley
Stephanie
S
Bian
Haikuo
H
Bauss
Frieder
F
Kim
Harry K W
HK
D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001847:Bone Diseases / Q000188:drug therapy*; D004164:Diphosphonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005269:Femur / Q000098:blood supply* / Q000187:drug effects; D000077557:Ibandronic Acid; D007238:Infarction / Q000188:drug therapy*; D013552:Swine
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid