Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.

An osteotropic alendronate-β-cyclodextrin conjugate (ALN-β-CD) was developed as a bonetargeting delivery system for improved treatment of skeletal diseases. The conjugate shows very strong binding to hydroxyapatite (HA, main component of the skeleton). Its ability in forming molecular inclusion complex with prostaglandins E 1 (PGE 1 , a potent bone anabolic agent) was confirmed by phase-solubility experiments and differential scanning calorimetry (DSC). In a bilateral rat mandible model, ALN-β-CD/PGE 1 molecular complex was shown to stimulate strong local bone anabolic reaction. In the control study, ALN-β-CD itself was also found to be bone anabolic. To investigate this finding, other control groups were studied. The histomorphometry data suggests that ALN-β-CD itself could generate more new bone at the injection site than its complex with PGE 1 . Alendronate (ALN) injection could also cause new bone formation, which locates peripheral to the site of injection. PGE 1 , saline or ethanol injections do not have anabolic effect. These findings were also confirmed by micro-CT evaluation of mandibular bones. It is clear that the bone anabolic effect of ALN-β-CD is independent of mechanical stimuli of the periosteum or ALN injection alone. Further studies are warranted to understand the working mechanism of ALN-β-CD as a bone anabolic agent.