Simvastatin therapy in higher dosages deteriorates bone quality: Consistent evidence from population-wide patient data and interventional mouse studies

Leutner, Michael; Butylina, Maria; Matzhold, Caspar; Klimek, Peter; Cuhaj, Carina; Bellach, Luise; Baumgartner‐Parzer, Sabina; Reiter, Birgit; Preindl, Karin; Kautzky, Alexander; Stimpfl, Thomas; Thurner, Stefan; Pietschmann, Péter; Fürnsinn, Clemens; Kautzky‐Willer, Alexandra

doi:10.1016/j.biopha.2022.114089

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…They concluded that high-dose simvastatin reduces bone quality in obese male and ovariectomized female mice, suggesting that direct drug action accounts for the association between high dosage and increased risk of osteoporosis as observed in comparable human cohorts [69]. In parallel, other works have highlighted the beneficial effect of sub-gingival delivery of simvastatin and rosuvastatin for treatment of chronic periodontitis with diabetes mellitus [70]. On the other hand, recently prospective randomized split-mouth study was done to assess the efficacy of simvastatin in bone regeneration in extraction sockets of mandibular third molars using cone beam computed tomography (CBCT) at 6th post-operative month, and it was demonstrated a statistically significant beneficial difference in bone regeneration with simvastatin treatment [71].…”

Section: Rt-pcr and Analysis Of The Expression Of Tumor Necrosis Fact...mentioning

confidence: 97%

Influence of Statins and Fibrates Drugs on Bone Health and Regeneration

Santiago,

Ruggieri,

Paulini

et al. 2024

JBNB

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In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition; in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer's disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin,

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Section: Rt-pcr and Analysis Of The Expression Of Tumor Necrosis Fact...mentioning

confidence: 97%

Influence of Statins and Fibrates Drugs on Bone Health and Regeneration

Santiago,

Ruggieri,

Paulini

et al. 2024

JBNB

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show abstract

“…474 There is evidence of an inverse relationship between cholesterol values and BMD, and there is also an association between low bone quality and diet-induced hyperlipidemia. 474,475 The increased risk of osteoporosis in patients diagnosed with hyperlipidemia might be attributed to the inflammatory status and oxidative stress promoted by cholesterol and fatty acids, which lead to greater osteoclastic activity with less bone formation and vascularization. 474,476 It has been reported that statins may have protective effects on bone, as these substances seem to increase the expression of BMP-2 474,477 and protect osteoblasts from apoptosis.…”

Section: Metabolicsyndromementioning

confidence: 99%

“…474,475 The increased risk of osteoporosis in patients diagnosed with hyperlipidemia might be attributed to the inflammatory status and oxidative stress promoted by cholesterol and fatty acids, which lead to greater osteoclastic activity with less bone formation and vascularization. 474,476 It has been reported that statins may have protective effects on bone, as these substances seem to increase the expression of BMP-2 474,477 and protect osteoblasts from apoptosis. 478 A previous review of the literature concluded that simvastatin was beneficial in the treatment of osteoporosis and had a positive effect on bone fracture healing.…”

Section: Metabolicsyndromementioning

confidence: 99%

Section: Host‐related Factors Altering Bone Metabolismmentioning

confidence: 99%

“…It is clear that, in general, hyperlipidemia and osteoporosis are linked in many of the same patients 474 . There is evidence of an inverse relationship between cholesterol values and BMD, and there is also an association between low bone quality and diet‐induced hyperlipidemia 474,475 . The increased risk of osteoporosis in patients diagnosed with hyperlipidemia might be attributed to the inflammatory status and oxidative stress promoted by cholesterol and fatty acids, which lead to greater osteoclastic activity with less bone formation and vascularization 474,476 .…”

Section: Host‐related Factors Altering Bone Metabolismmentioning

confidence: 99%

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Emerging factors affecting peri‐implant bone metabolism

Insua,

Galindo‐Moreno,

Miron

et al. 2023

Periodontology 2000

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Implant dentistry has evolved to the point that standard implant osseointegration is predictable. This is attributed in part to the advancements in material sciences that have led toward improvements in implant surface technology and characteristics. Nonetheless, there remain several cases where implant therapy fails (specifically at early time points), most commonly attributed to factors affecting bone metabolism. Among these patients, smokers are known to have impaired bone metabolism and thus be subject to higher risks of early implant failure and/or late complications related to the stability of the peri‐implant bone and mucosal tissues. Notably, however, emerging data have unveiled other critical factors affecting osseointegration, namely, those related to the metabolism of bone tissues. The aim of this review is to shed light on the effects of implant‐related factors, like implant surface or titanium particle release; surgical‐related factors, like osseodensification or implanted biomaterials; various drugs, like selective serotonin reuptake inhibitors, proton pump inhibitors, anti‐hypertensives, nonsteroidal anti‐inflammatory medication, and statins, and host‐related factors, like smoking, diet, and metabolic syndrome on bone metabolism, and aseptic peri‐implant bone loss. Despite the infectious nature of peri‐implant biological complications, these factors must be surveyed for the effective prevention and management of peri‐implantitis.

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Hyperlipidemia and osteoporosis

Leutner

2023

J. Klin. Endokrinol. Stoffw.

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ZusammenfassungDie aktuelle Datenlage zeigt auf, dass es einen Zusammenhang zwischen Hyperlipidämien und dem Knochenstoffwechsel gibt. Dieser Zusammenhang scheint auch abhängig von den Konzentrationen der Lipidparameter zu sein. Klare Evidenz dafür, dass Statine einen osteoprotektiven Effekt auf den Knochenstoffwechsel haben, gibt es bisher nicht. Rezente Entwicklungen zeigen, dass es hier dosisabhängige Zusammenhänge von verschieden potenten Statinen mit dem Knochenstoffwechsel geben könnte. Insgesamt gilt es zu untersuchen, ob der Zusammenhang von Hyperlipidämien mit dem Knochenstoffwechsel durch direkte Statineffekte und/oder durch die Konzentrationen der verschiedenen Lipidparameter gesteuert wird.

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Simvastatin therapy in higher dosages deteriorates bone quality: Consistent evidence from population-wide patient data and interventional mouse studies

Cited by 11 publications

References 27 publications

Influence of Statins and Fibrates Drugs on Bone Health and Regeneration

Influence of Statins and Fibrates Drugs on Bone Health and Regeneration

Emerging factors affecting peri‐implant bone metabolism

Hyperlipidemia and osteoporosis

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