Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions

Oryan, Ahmad; Kamali, Amir; Moshiri, Ali

doi:10.1016/j.jconrel.2015.07.022

Cited by 118 publications

(116 citation statements)

References 136 publications

(350 reference statements)

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“…Because bone healing is an orchestrated process that occurs normally after each injury and also Simvastatin has low affinity to bone, it is necessary to maintain the effective concentrations of Simvastatin in the circulating blood for a long time to be sure that Simvastatin is able to continuously affect the injured healing bone. 1 Therefore, in the systemic approach, Simvastatin needs to be continuously administered for a long period of time, which increases the total dose that is required in bone regeneration.…”

Section: Route Of Administrationmentioning

confidence: 99%

“…1,2,4,105,106 Synthetic materials such as polylactide co glycolic acid (PLGA), poly lactic acid (PLA) and poly caprolactone (PCL) are polymeric in nature. 4,[107][108][109] As these biomaterials have controllable biodegradation, they are normally used for controlled delivery of Simvastatin.…”

Section: Biomaterials Used To Locally Deliver Simvastatinmentioning

confidence: 99%

“…1,2 In the last two decades, scientists have found that statins have other mechanisms that may be beneficial in bone regeneration. 3 Lipophilic statins such as Simvastatin increase osteogenesis by enhancing differentiation of mesenchymal cells into osteoblasts, upregulating bone morphogenetic protein-2 (BMP-2) and down regulating osteoblast apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…4 Thus, statins such as Simvastatin have been suggested as a dual-mode action drug. 1 Although Simvastatin is not a new generation of the statin family, it is the most investigated statin family member in the field of bone research, particularly in animal models. [5][6][7][8][9][10][11][12][13] However, the mechanisms, route of administration, dose and dosages, and effectiveness of Simvastatin have not been clearly defined in different in vivo studies on bone repair and osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12][13] However, the mechanisms, route of administration, dose and dosages, and effectiveness of Simvastatin have not been clearly defined in different in vivo studies on bone repair and osteoporosis. 1 In addition, some controversial results regarding the role of Simvastatin on bone metabolism are seen in the literature. On this basis, we are motivated to review all the important in vivo studies that have used Simvastatin to either treat osteoporosis or accelerate and enhance bone regeneration.…”

Section: Introductionmentioning

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: Route Of Administrationmentioning

confidence: 99%

Section: Biomaterials Used To Locally Deliver Simvastatinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Spatiotemporal Control Strategies for Bone Formation through Tissue Engineering and Regenerative Medicine Approaches

White

Olabisi

2018

Adv Healthcare Materials

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Global increases in life expectancy drive increasing demands for bone regeneration. The gold standard for surgical bone repair is autografting, which enjoys excellent clinical outcomes; however, it possesses significant drawbacks including donor site morbidity and limited availability. Although collagen sponges delivered with bone morphogenetic protein, type 2 (BMP2) are a common alternative or supplement, they do not efficiently retain BMP2, necessitating extremely high doses to elicit bone formation. Hence, reports of BMP2 complications are rising, including cancer promotion and ectopic bone formation, the latter inducing complications such as breathing difficulties and neurologic impairments. Thus, efforts to exert spatial control over bone formation are increasing. Several tissue engineering approaches have demonstrated the potential for targeted and controlled bone formation. These approaches include biomaterial scaffolds derived from synthetic sources, e.g., calcium phosphates or polymers; natural sources, e.g., bone or seashell; and immobilized biofactors, e.g., BMP2. Although BMP2 is the only protein clinically approved for use in a surgical device, there are several proteins, small molecules, and growth factors that show promise in tissue engineering applications. This review profiles the tissue engineering advances in achieving control over the location and onset of bone formation (spatiotemporal control) toward avoiding the complications associated with BMP2.

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Statin use in patients with type 2 diabetes has lower risk of hip fractures: A Taiwan national population‐based study

Lee

Chen

Lin

et al. 2023

Diabetes Metabolism Res

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Aims Type 2 diabetes mellitus (T2DM) frequently co‐exists with osteoporosis and dyslipidemia. Statins have been commonly used in the treatment of dyslipidemia. Recent studies have indicated a therapeutic role of statins in decreasing the risk of osteoporosis and fractures, but conflicting results have been reported. This study investigated the association between statin use and hip fracture (HFx) risk among T2DM patients. Materials and Methods A retrospective Taiwan population‐based propensity‐matched cohort study was performed using the Diabetes Mellitus Health Database from Taiwan National Health Insurance Research Database. Patients with newly diagnosed with T2DM between 2010 and 2014 were identified. Patients who previously used statins and had ever suffered HFx before the index date were excluded. HFx that occurred from 2010 to 2019 was collected to compute the cumulative rate of HFx. Hazard ratios (HRs) were calculated for the HFx risk according to the use or non‐use of statins. To evaluate the dose–effect relationship of statins, sensitivity analyses were conducted. Results After propensity score matching for age and sex, 188,588 patients were identified as statin users and non‐statin users. Statin use after T2DM diagnosis was associated with a decreased HFx risk with an adjusted HR (aHR) of 0.69 (P < 0.001). A dose–effect relationship was identified. The aHRs for developing HFx were 1.29, 0.67, and 0.36 for patients who used 28–174, 175–447, and >447 cumulative defined daily doses of statins, respectively (P < 0.001). Conclusions Statin use in adults with T2DM showed a lower risk of HFx by demonstrating a dose–response relationship.

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Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions

Cited by 118 publications

References 136 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

Spatiotemporal Control Strategies for Bone Formation through Tissue Engineering and Regenerative Medicine Approaches

Statin use in patients with type 2 diabetes has lower risk of hip fractures: A Taiwan national population‐based study

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