Effects of local simvastatin–alendronate conjugate in preventing periodontitis bone loss

Price, U.; Le, Hao; Powell, Sandi; Schmid, Marian J.; Marx, David B.; Zhang, Y.; Wang, D.; Narayana, Nagamani; Reinhardt, Richard

doi:10.1111/jre.12036

Cited by 30 publications

(35 citation statements)

References 50 publications

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“…Of the 17 studies, only 29.41 locally injected Simvastatin via different carriers while 70.59% locally implanted either scaffolds or microspheres which were loaded with Simvastatin in order to gradually release the drug in the injured area. Local injection of 0.5 mg Simvastatin was the most effective concentration in promoting bone repair in rats 42,49,80 and miniature pigs 59 ; the concentration of 2.5 mg was effective for the same purpose in rabbits 56 and the concentration of 10 mg seems to be effective in promoting bone repair in canine 54 ( Table 5). Of the 12 studies that locally delivered Simvastatin via different carriers, doses of 0.5 and 2.5 mg Simvastatin/scaffold were the optimum concentrations required for bone repair in rats and rabbits, respectively.…”

Section: Dose and Dosage Of Simvastatin In Maxillofacial Modelsmentioning

confidence: 99%

“…11,25,29,40,113,116,117 As another strategy, Simvastatin can be conjugated with free molecular sites of the bone scaffolds or chemical compounds (that have high affinity to bone such as bisphosphonates). 42,49,88 This method is currently under development and would be a valuable strategy in the near future. In another method, Simvastatin can be polymerized in combination with other polymers as a fibre.…”

Section: Drug Delivery Systems Used In Simvastatin Therapymentioning

confidence: 99%

“…, two studies used platelet rich plasma (PRP) + Simvastatin 41,63 and three studies used alendronate with Simvastatin. 42,49,88 Platelet rich plasma (PRP) and its other forms (gel and glue) can be obtained from patients' anticoagulant peripheral blood by one or two step centrifugation. 107,119,[121][122][123] PRPs are different from each other based on their platelet concentration which is 1.5 to 10 times greater than the physiologic plasma.…”

Section: Co-administration Of Healing Promotive Factors and Stem Cellmentioning

confidence: 99%

“…Similar to other bisphosphonates, it is chemically related to inorganic pyrophosphate, the endogenous regulator of bone turnover, but while pyrophosphate inhibits both osteoclastic bone resorption and mineralization of the new bone, alendronate specifically inhibits bone resorption without any effect on mineralization at pharmacologically achievable doses. 42,49,88 Some researchers have suggested that Alendronate should be used with Simvastatin in order to reduce the degree of bone loss because they thought that Simvastatin, although having beneficial effects on osteogenesis, has no strong inhibitory effects on osteoclastogenesis. 42,49,88 Stem cells are used to enhance bone regeneration, however, stem cell therapy has several technical issues and is a developing field.…”

Section: Co-administration Of Healing Promotive Factors and Stem Cellmentioning

confidence: 99%

“…42,49,88 Some researchers have suggested that Alendronate should be used with Simvastatin in order to reduce the degree of bone loss because they thought that Simvastatin, although having beneficial effects on osteogenesis, has no strong inhibitory effects on osteoclastogenesis. 42,49,88 Stem cells are used to enhance bone regeneration, however, stem cell therapy has several technical issues and is a developing field. Simvastatin has been used with stem cells in order to promote osteoinduction and osteogenesis in vivo.…”

Section: Co-administration Of Healing Promotive Factors and Stem Cellmentioning

confidence: 99%

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Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

Moshiri

Sharifi

Oryan

2016

Clin Exp Pharma Physio

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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.

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Section: Dose and Dosage Of Simvastatin In Maxillofacial Modelsmentioning

confidence: 99%

Section: Drug Delivery Systems Used In Simvastatin Therapymentioning

confidence: 99%

Section: Co-administration Of Healing Promotive Factors and Stem Cellmentioning

confidence: 99%

Section: Co-administration Of Healing Promotive Factors and Stem Cellmentioning

confidence: 99%

Section: Co-administration Of Healing Promotive Factors and Stem Cellmentioning

confidence: 99%

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Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

Moshiri

Sharifi

Oryan

2016

Clin Exp Pharma Physio

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Future Perspectives of Bisphosphonates in Maxillofacial, Dental, and Medical Practice

Smeets

Hanken

Jung

et al. 2014

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The Evaluation of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model

et al. 2016

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Purpose To evaluate the therapeutic efficiency of a micellar prodrug formulation of simvastatin (SIM/SIM-mPEG) and explore its safety in a closed femoral fracture mouse model. Methods The amphiphilic macromolecular prodrug of simvastatin (SIM-mPEG) was synthesized and formulated together with free simvastatin into micelles. It was also labeled with a near infrared dye for in vivo imaging purpose. A closed femoral fracture mouse model was established using a three-point bending device. The mice with established closed femoral fracture were treated with SIM/SIM-mPEG micelle, using free simvastatin and saline as controls. The therapeutic efficacy of the micelles was evaluated using a high-resolution micro-CT. Serum biochemistry and histology analyses were performed to explore the potential toxicity of the micelle formulation. Results Near Infrared Fluorescence (NIRF) imaging confirmed the passive targeting of SIM/SIM-mPEG micelles to the bone lesion of the mice with closed femoral fracture. The micelle was found to promote fracture healing with an excellent safety profile. In addition, the accelerated healing of the femoral fracture also helped to prevent disuse-associated same-side tibia bone loss accompanying the femur fracture. Conclusion SIM/SIM-mPEG micelle was found to be an effective and safe treatment for closed femoral fracture repair in mice. The evidence obtained in this study suggests that it may have the potential to be translated into a novel therapy for clinical management of skeletal fractures and non-union.

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Effects of local simvastatin–alendronate conjugate in preventing periodontitis bone loss

Abstract: The primary conclusion of this study was that locally applied SIM-ALN-CD has the potential to prevent episodes of periodontitis bone loss.

Cited by 30 publications

References 50 publications

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

Future Perspectives of Bisphosphonates in Maxillofacial, Dental, and Medical Practice

The Evaluation of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model

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