Retention, Distribution, and Effects of Intraosseously Administered Ibandronate in the Infarcted Femoral Head

Abstract

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.Introduction: 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. Materials and Methods: IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject

Femoral Head Deformation and Repair Following Induction of Ischemic Necrosis

“…The piglet model leads to femoral head deformity similar to Legg-Calvé-Perthes disease 1,2,4,5,[22][23][24] , with histologic changes characteristic of human cases [25][26][27][28][29][30][31][32][33] . Studies from humans with the disease have recognized the changes to be intermingling of necrosis and repair 25,27 , new bone formation by intramembranous ossification 30 , increased thickness of the surface cartilage 31 , retained shape and internal structure of the most medial portion of the head, and (in the central and lateral aspects of the head) a callus-like fibrocartilage, vascular granulation tissue, new bone formation on necrotic trabeculae, and chondroid tissue 32,33 .…”

“…The model differs in two important ways from Legg-Calvé-Perthes disease: (1) it induces complete ischemia rapidly by a mechanism different from that in humans, in whom periosseous vascular constriction has not been implicated, and (2) it involves a single event to induce ischemia, while there is evidence that at least some humans experience two or more episodes of ischemia on the basis of the histologic finding of necrosis of repair tissue 39,40 . The model has been helpful in demonstrating that femoral head deformation can be minimized by preventing osteoclastic bone resorption with use of bisphosphonates systemically 22 or by intraosseous injection 23 or by inducing osteoclast inhibition by other means 24 . This study demonstrates the ability of magnetic resonance imaging to assess the model in vivo and can be applied to gain further information about the development and prevention of deformity following ischemic insults.…”

Evidence for Using Bisphosphonate to Treat Legg-Calvé-Perthes Disease

“…The study, however, lacked a control group. In the studies examining the patients with leukemia or malignancy, a long-term radiographic benefit from BPs was not observed in three of six patients needing Volume The experimental studies looking at BP therapy of femoral head deformity consisted of both small-animal [28,29,34,35] and large-animal [3,12,17,45] models of femoral head ischemia (Table 3). In immature rats, the effects of zoledronic acid (the most potent aminobisphosphonate clinically available) were investigated in a surgically induced osteonecrosis model and in spontaneously hypertensive rats that develop a LCPD-like osteonecrosis.…”

“…This finding explains why multiple dosing regimens are suggested for oral or intravenous administration. Local intraosseous administration has been investigated in the piglet model by injecting 14 C-ibandronate into the necrotic femoral heads and demonstrated a wide distribution of the drug with a reasonable retention over time [3] (Fig. 6).…”

“…This left eight articles for full review by three reviewers (HKWK, DGL, MLY) [3,12,17,28,29,34,35,45] (Fig. 3).…”