Alendronate-hydroxyapatite nanocomposites and their interaction with osteoclasts and osteoblast-like cells

The direct synthesis of hydroxyapatite in the presence of bisphosphonates is quite difficult due to the great affinity for calcium of these compounds, which are widely used in the treatment of pathologies related to bone loss. We recently developed a new method which allowed to synthesize alendronate-hydroxyapatite composite nanocrystals with a bisphosphonate content up to about 7 wt%. Herein we report the results of an in vitro study aimed to investigate the effects of alendronate incorporation into hydroxyapatite on bone cells response. Osteoblast-like MG63 cells and human osteoclasts were cultured on nanocrystals at different alendronate content (3.9, 6.2, 7.1 wt%). MG63 cells cultured on the composite nanocrystals display normal morphology, good proliferation and increased values of the differentiation parameters. In particular, when cultured on composites at relatively high alendronate contents, osteoblasts display increased values of alkaline phosphatase activity (ALP), collagen type I, and osteocalcin production, as well as significant decrease of matrix metalloproteinases (MMP-1 and MMP-13) production, with respect both to the control and to pure hydroxyapatite nanocrystals. It follows that the presence of alendronate enhances osteoblast activation and extracellular matrix mineralization processes, without any abnormal collagen degradation. The osteoclast number on the composite nanocrystals decrease indicating that the bisphosphonate exerts its inhibitory effect on osteoclast proliferation even when incorporated into hydroxyapatite.