Bone Abstracts

In 1999 Mundy et al. showed that simvastatin, a drug administered for high cholesterol levels, had a profound stimulatory effect on osteoblasts. Since then other studies have also confirmed that simvastatin enhances bone formation; however, the lack of a local delivery system have restricted its clinical use. We have used premixed acidic calcium phosphate cement as a local delivery system for simvastatin. To confirm that the simvastatin released retained its activity, in vitro studies were preformed. We measured how cell proliferation and differentiation was affected by different doses of simvastatin as well as their ability to quench reactive oxygen species (ROS) production.

Different doses of simvastatin were added to the liquid phase of calcium phosphate cement consisting of β-tricalcium phosphate, monocalcium phosphate anhydrous, and glycerol. The cements were moulded and soaked in PBS. At specified time points PBS was collected and used for cell studies. Saos-2 (human osteoblastic cell-line), and THP-1 (human monocytic cell-line) were seeded in tissue culture plates after which the cement extracts were added to the cells at different time points. The proliferation, measured by Alamarblue, and differentiation, measured by alkaline phosphatase activity (ALP), was quantified for Saos-2 cells after 3, 5, and 7 days. The total ROS production for THP-1 was measured after 24 h by means of luminol amplified chemiluminescence.

The in vitro studies revealed that the simvastatin released from the cements was still active and able to stimulate osteoblast differentiation. It also had the capability to quench ROS production. In conclusion simvastatin can be added to acidic calcium phosphate cements to increase the osteogenic properties and decrease the inflammatory response.