Alendronate inhibits triglyceride accumulation and oxidative stress in adipocytes and the inflammatory response of macrophages which are associated with adipose tissue dysfunction

Martini, Claudia; Sosa, Fernando Nicolas; Malvicini, Ricardo; Pacienza, Natalia; Yannarelli, Gustavo; Vila, María del Carmen

doi:10.1007/s13105-021-00826-9

Cited by 6 publications

(4 citation statements)

References 45 publications

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“…How alendronate influences on glucose metabolism is not clarified. In vitro studies suggest that alendronate decreases adipogenesis and activates lipolysis (30,31), conditions that may be altered in subjects with decreased insulin sensitivity. Furthermore, a boneresorption-specific impact on insulin signaling by Osteocalcin has been suggested, though the evidence for an effect in humans is very limited and the hypothesis is based on an animal model (32).…”

Section: Discussionmentioning

confidence: 99%

Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study

et al. 2021

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ObjectiveA link has been proposed between glucose homeostasis and bone metabolism. Bisphosphonates are first-line treatment of osteoporosis, and we aimed to investigate whether the risk of developing type 2 diabetes was associated with prior use of alendronate.Research Design and MethodsWe conducted a population-based nested case-control study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. All cases with a diagnosis of type 2 diabetes between 2008 and 2018 were matched on sex and age with 3 randomly selected controls by incidence-density sampling. Exposure was defined as ever use of alendronate and further grouped as effective and compliant use. ORs were calculated by conditional logistic regression analysis with adjustment for several confounders and test for trend for dose-response relationship.ResultsWe included 163,588 patients with type 2 diabetes and 490,764 matched control subjects with a mean age of 67 years and 55% male subjects. The odds of developing type 2 diabetes were lower among ever users of alendronate (multiple adjusted OR: 0.64 [95% CI 0.62-0.66]). A test for trend suggested a dose-response relationship between longer effective use of alendronate and lower risk of type 2 diabetes.ConclusionThese results suggest a possible protective effect of alendronate in a dose-dependent manner against development of type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study

et al. 2021

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“…The levels of triglycerides were obviously different among the normal, osteopenia and osteoporosis groups ( 71 ), which indicated that variations in triglycerides were strongly related to the occurrence and development of osteoporosis ( 72 ). Some drugs for the treatment of osteoporosis, such as bisphosphonates and calcium, have also been found to cause abnormal triglyceride metabolism in adipose tissue while promoting bone growth, showing that interfering with fat metabolism is beneficial for improving bone mass ( 73 , 74 ). At the cellular level, the adipogenic differentiation of BM-MSCs leads to the accumulation of triglycerides, which are a risk factor for osteogenesis ( 75 ).…”

Section: Lipids and Osteoporosismentioning

confidence: 99%

Obesity and lipid metabolism in the development of osteoporosis (Review)

Wang,

Zhang,

Zhao

et al. 2024

Int J Mol Med

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Osteoporosis is a common bone metabolic disease that causes a heavy social burden and seriously threatens life. Improving osteogenic capacity is necessary to correct bone mass loss in the treatment of osteoporosis. Osteoblasts are derived from the differentiation of bone marrow mesenchymal stem cells, a process that opposes adipogenic differentiation. The peroxisome proliferator-activated receptor γ and Wnt/β-catenin signaling pathways mediate the mutual regulation of osteogenesis and adipogenesis. Lipid substances play an important role in the occurrence and development of osteoporosis. The content and proportion of lipids modulate the activity of immunocytes, mainly macrophages, and the secretion of inflammatory factors, such as IL-1, IL-6 and TNF-α. These inflammatory effectors increase the activity and promote the differentiation of osteoclasts, which leads to bone imbalance and stronger bone resorption. Obesity also decreases the activity of antioxidases and leads to oxidative stress, thereby inhibiting osteogenesis. The present review starts by examining the bidirectional differentiation of BM-MScs, describes in detail the mechanism by which lipids affect bone metabolism, and discusses the regulatory role of inflammation and oxidative stress in this process. The review concludes that a reasonable adjustment of the content and proportion of lipids, and the alleviation of inflammatory storms and oxidative damage induced by lipid imbalances, will improve bone mass and treat osteoporosis. Contents1. Introduction 2. Obesity-induced osteoporosis 3. Balance of osteogenesis and adipogenesis 4. Hyperlipemia-induced pathological changes and osteoporosis 5. Lipids and osteoporosis 6. Obesity in postmenopausal osteoporosis 7. Lipid metabolism disorders in osteoporotic patients with diabetes 8. discussion

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“…However, analyzing the publication in detail reveals several issues that may indeed question the external validity of the findings (156). A complete understanding of the underlying mechanism is still lacking but one in vitro study suggests that alendronate contributes to the prevention of oxidative stress and inflammation in adipocytes (157). Hence, alendronate could potentially impede the progression of adipose tissue dysfunction and insulin resistance.…”

Section: Impact On Glucose Metabolismmentioning

confidence: 99%

“…How alendronate impact on glucose metabolism is yet to be clarified. In vitro studies have suggested a decrease in adipogenesis and activation of lipolysis (157,220), conditions suggested altered in subjects with impaired insulin sensitivity and at risk of type 2 diabetes.…”

Section: Anti-osteoporotic Therapies and Glucose Metabolismmentioning

confidence: 99%

TYPE 2 DIABETES AND BONE HEALTH: an epidemiological approach

Viggers

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Alendronate inhibits triglyceride accumulation and oxidative stress in adipocytes and the inflammatory response of macrophages which are associated with adipose tissue dysfunction

Cited by 6 publications

References 45 publications

Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study

Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study

Obesity and lipid metabolism in the development of osteoporosis (Review)

TYPE 2 DIABETES AND BONE HEALTH: an epidemiological approach

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