Statin released by means of tricalcium phosphate lysine delivery system in a defect and segmental femoral injury in an animal model

Statins, which are 3 -hydroxy-3 -methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hyperlipidemia, and are largely metabolized in the liver. Recent studies and animal data suggest that statins promote osteogenesis and increase bone strength. Physiologically, marked reduction in total cholesterol level may interfere with the synthesis of reproductive and adrenal hormones. However, little is known about the effects of statins delivered by sustained delivery system to a target site of a defect and segmental bone fractures on the morphology of the liver and adrenal gland. Therefore, the purpose of this study was to develop a targeted statin delivery system using Tricalcium Phosphate Lysine (TCPL) for defect and segmental femoral injuries and evaluate the effects on the injured bones and on the histomorphology of the liver and adrenal after sustained delivery of statin for a period of 30 days and 12 weeks post-surgery. At the end of 30 days (Phase I), and 12 weeks (Phase II), all the animals were euthanized (with overdose of halothane). The vital organs (including the liver and adrenal), reproductive organs, and the femoral bones were collected for histomorphological analysis. Simvastatin used in this study significantly increased fracture healing in both phases. However, in Phase I study, the adrenal wet weight recorded in the statin group was slightly higher than the weights recorded for the sham and the control groups, but the difference was not statistically significant (p = 0.157). Also, there was atrophy of the zona fasciculata and the zona reticularis, and compensatory hypertrophy of the medulla of the adrenal glands in the samples taken from two of the rats in Phase I. In addition, the wet weight of the liver in the statin group was not significantly different from the control and the sham groups (p = 0.320), although, there was an insignificant decrease of the wet weight compared to the control and sham groups. The histomorphological evaluation by the Image pro digital analysis showed that the liver morphology was different from the control. There appeared to be an atrophy of the liver, with a denser appearance compared to the control and sham groups (Phase I). In Phase II study, there were no significant morphological and wet weight differences of the liver and adrenal glands in the statin group compared to the control and sham groups. In conclusion, sustained delivery of statin in a short period may lead to alteration of the histomorphology of the liver and adrenal gland in a rat model and with adaptation to normal morphology after a long period of sustained delivery of statin. Keywords: Statins, Fracture, Healing, Drug Delivery System, Tricalcium Phosphate Lysine, Simvastatin, morphological changes, biochemical markers.
INTRODUCTION Reproductive hormonal levels may be influenced by the levels or the bioavailability of cholesterol. Estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway [4]. There is [...]