Novel applications of statins for bone regeneration

Abstract

The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering.

Statins in nonsurgical and surgical periodontal therapy. A systematic review and meta‐analysis of preclinical in vivo trials

“…In particular, statins are shown to be effective against A. actinomycetemcomitans and Porphyromonas gingivalis , 2 of the major species of bacteria implicated in periodontitis pathogenesis. Furthermore, statins are shown to inhibit tissue‐degrading enzymes (i.e., matrix metalloproteinases) and to exert a pro‐proliferative effect on mesenchymal stromal cells and endothelial progenitor cells . Statins are also shown to enhance osteoblastic differentiation and viability, bone morphogenetic protein and vascular endothelial growth factor expression and to interfere with bone resorption and osteoclastogenesis …”

“…Statins present high efficacy and tolerability in general, are rather inexpensive and by inhibiting cholesterol synthesis reduce the risk for cardiovascular diseases . Besides reducing cholesterol levels, statins have also been shown to possess antimicrobial, antiviral, fungicidal, anti‐inflammatory and pro‐osteogenic properties and to enhance the number and/or function of mesenchymal stromal cells and/or endothelial progenitor cells; thus, statins appear relevant in periodontology, either in preventing disease or in periodontal therapy.…”

Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent

“…Many studies have reported the benefits of statins, especially SIM, on bone formation as well as on the inhibition of bone resorption (Horiuchi & Maeda, ; Moshiri, Sharifi, & Oryan, ; Mundy, ; Shah, Werlang, Kasper, & Mikos, ; Zhang et al, ). Within the family of statins, PITA presents some interesting properties, in particular its lower price, hydrophilic properties and its comparable efficiency compared to other statins (i.e., SIM) at much lower concentrations.…”

Tissue Engineering in Orthopaedics

“…Chemical cues may promote healing by influencing the inflammatory pathway (such as statins 25 ) or by directly acting on cells (such as site-specific bisphosphonate therapy 26 ). Locally delivered small molecules for bone tissue engineering is a growing area of interest in the regenerative medicine community 27 .…”