Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations

Abstract

SUMMARYSimvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.

Hydroxychloroquine decreases human MSC‐derived osteoblast differentiation and mineralization in vitro

“…Indeed, both in vitro and in vivo studies have reported the beneficial effects of statins on osteoblast differentiation and mineralization . Additionally, in vivo studies showed that statins are a potential treatment for osteoporosis . Based on these studies, we expected to find improved MSC‐derived osteoblast differentiation and/or mineralization and we speculated that SIM may antagonize the negative effects of HCQ.…”

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.…”

Bone Loss in HIV Infection

“…There is one case report of successful teriparatide use in an HIV-infected man with severe osteoporosis [123] although robust data regarding its use in HIV-infected patients are lacking. In addition, the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) simvastatin has been shown to increase osteoblast activity and decrease osteoclastogenesis, and is associated with increased fracture healing in in vivo animal models [124], while pravastatin has been shown to prevent PI-induced senescence in MSCs and restore osteoblastic potential in vitro [89]. Clinically however, in HIV-infected individuals on stable cART who had heightened immune activation, treatment with rosuvastatin for 96 weeks was not associated with any changes in BMD, although it was associated with improvement in lean body mass [125].…”