The effect of zoledronate-hydroxyapatite nanocomposites on osteoclasts and osteoblast-like cells in vitro.

This study demonstrates that zoledronate containing hydroxyapatite nanocrystals (HA-ZOL) can be synthesized as a single crystalline phase up to a zoledronate content of about 7 wt % by direct synthesis in aqueous solution, at variance with what previously found for alendronate-hydroxyapatite nanocrystals (HA-AL). On increasing zoledronate incorporation, the length of the coherent crystalline domains and the crystal dimensions of hydroxyapatite decrease, whereas the specific surface area increases. Full profile fitting of the powder X-ray diffraction patterns does not indicate major structural modifications, but an increase of the hydroxyapatite unit cell, on increasing zoledronate content. These data, together with a structural similarity between hydroxyapatite and calcium zoledronate, suggest a preferential interaction between zoledronate and the hydroxyapatite faces parallel to the c-axis direction. Osteoblast-like MG63 cells and human osteoclasts were cultured on HA-ZOL nanocrystals and as a comparison on HA-AL nanocrystals containing almost the same (about 7 wt %) bisphosphonate amount. The beneficial influence of bisphosphonates on osteoblast proliferation and differentiation is enhanced when the tests are performed in co-cultures. Similarly, the reduction of osteoclast proliferation and the increase of Caspase-3 production are dramatically enhanced in co-cultures, which highlight an even greater influence of HA-ZOL than HA-AL on osteoclast apoptosis.