Metformin use is associated with a lower risk of osteoporosis in adult women independent of type 2 diabetes mellitus and obesity. REDLINC IX study

Blümel, Juan E.; Arteaga, Eugenio; Aedo, Sócrates; Arriola-Montenegro, José; López, Marcela; Martino, Mabel; Miranda, Carlos; Miranda, Octavio; Mostajo, Desireé; Ñañez, Mónica; Ojeda, Eliana; Susana, Pilnik; Rojas, José Luis Vázquez; Salinas, Carlos Aguilar; Sosa, Lida; Spritzer, Poli Mara; Tserotas, Konstantinos; Vallejo, María S.; Belardo, Alejandra; Fighera, Tayane Muniz; Chedraui, Peter

doi:10.1080/09513590.2020.1718092

Cited by 28 publications

(14 citation statements)

References 27 publications

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“…At the same time, we have also observed that the use of metformin alone can improve the bone microstructure of the spine than the diabetes group. Consistent with the literature, this research found that participants who reported that metformin use is involved in a lower risk of osteoporosis in adult women independent of type 2 diabetes mellitus and obesity [11,41]. This also accords with our earlier observations, which showed that the metformin decreased bone turnover marker and influence bone formation in clinical studies [42,43].…”

Section: Discussionsupporting

confidence: 92%

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Zhou

Guan

Liu

et al. 2022

Aging

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Background: To explore the anti-osteoporosis and anti-diabetes effects and potential underlying mechanisms of treatment with metformin and alendronate in diabetes mellitus mice. Methods: Eight-week-old C57 BL/KS db/db and db/+ female mice were evaluated according to the following treatment group for 12 weeks: control group, diabetes mellitus group, diabetes mellitus with metformin group, diabetes mellitus with Alendronate group, diabetes mellitus with metformin plus alendronate group. Glucose level, glucose tolerance test, bone mineral density, bone microarchitecture, bone histomorphometry, serum biomarkers, and qPCR analysis. Results: Combined metformin and alendronate can improve progression in glucose metabolism and bone metabolism, including blood glucose levels, blood glucose levels after 4 and 16 hours fasting, glucose tolerance test results, insulin sensitivity and reduces bone loss than the diabetes group. The use of alendronate alone can increase significantly serum glucagon-like peptide-1 levels than the diabetes group. The use of metformin alone can improve bone microstructure such as Tb.Sp and Tb.N of spine in diabetic mice. Conclusion: The combined use of alendronate and metformin has an anti-diabetes and anti-osteoporotic effect compared with diabetic mice, but they appear to act no obvious synergistically between alendronate and metformin.

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Section: Discussionsupporting

confidence: 92%

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

Zhou

Guan

Liu

et al. 2022

Aging

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“…MF also inhibits advanced glycation end product (AGE), which can promote bone turnover [ 13 ]. A recent study even suggests that MF is beneficial for bone health in adult women without T2DM and obesity [ 14 ]. Since its discovery, MF has shown desirable lipid-lowering activity [ 10 ] and cardio-protective effect [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis

Aung¹,

Amin²,

Gulraiz³

et al. 2020

Cureus

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As a worldwide aging population is on the rise, osteoporosis (OS) is becoming a global health burden. Therefore, many researchers and health authorities are looking into the potential prevention and treatment of OS. Although previously regarded as two separate pathological processes, diabetes (DM) and OS are now regarded as two conditions that can occur together. It is now believed that OS can develop as a complication of DM. This relationship is further evidenced through a reduction in bone mineral density in type-1 diabetes with a resulting increased risk of fracture. Although bone mineral density in type-2 diabetes mellitus is normal or increased, there is also increased fragility due to decreased bone quality. These abnormal bone qualities tend to occur through the production of reduced bone microvasculature and advanced glycation end product, AGE. Interestingly, one of the most common treatments for DM, metformin (MF), shows a promising result on the protection of diabetes and non-diabetes related bone turnover. It is believed that MF modulates its effect through the adenosine monophosphate-activated protein kinase (AMPK) pathway. Recent data regarded AMPK as a vital mediator of homeostasis. It is involved not only in glucose metabolism but also in osteogenesis. AMPK can directly influence the production of mature and good quality bone by decreasing osteoclasts, increasing osteoblast formation, and enhancing bone mineral deposition. As an activator of AMPK, MF also upregulates osteogenesis. Furthermore, MF can influence osteogenesis through a non-AMPK pathway, such as the fructose 1-6 phosphatase pathway, by reducing glucose levels. While already recognized as a safe and effective treatment for DM, this article discusses whether MF can be used for the prevention and treatment of OS.

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“…Similarly, another study identified a small but positive effect of metformin treatment on the mineral content and density of peripheral bone ( Nordklint et al, 2021 ). Notably, some researchers proposed that metformin administration was associated with a decreased risk of osteoporosis in adult women, regardless of whether they had type 2 diabetes or were obese ( Blümel et al, 2020 ).…”

Section: Protective Effects Of Metformin In the Musculoskeletal Systemmentioning

confidence: 99%

The Function of Metformin in Aging-Related Musculoskeletal Disorders

Song

Zhao

2022

Front. Pharmacol.

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Metformin is a widely accepted first-line hypoglycemic agent in current clinical practice, and it has been applied to the clinic for more than 60 years. Recently, researchers have identified that metformin not only has an efficient capacity to lower glucose but also exerts anti-aging effects by regulating intracellular signaling molecules. With the accelerating aging process and mankind’s desire for a long and healthy life, studies on aging have witnessed an unprecedented boom. Osteoporosis, sarcopenia, degenerative osteoarthropathy, and frailty are age-related diseases of the musculoskeletal system. The decline in motor function is a problem that many elderly people have to face, and in serious cases, they may even fail to self-care, and their quality of life will be seriously reduced. Therefore, exploring potential treatments to effectively prevent or delay the progression of aging-related diseases is essential to promote healthy aging. In this review, we first briefly describe the origin of metformin and the aging of the movement system, and next review the evidence associated with its ability to extend lifespan. Furthermore, we discuss the mechanisms related to the modulation of aging in the musculoskeletal system by metformin, mainly its contribution to bone homeostasis, muscle aging, and joint degeneration. Finally, we analyze the protective benefits of metformin in aging-related diseases of the musculoskeletal system.

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Metformin use is associated with a lower risk of osteoporosis in adult women independent of type 2 diabetes mellitus and obesity. REDLINC IX study

Cited by 28 publications

References 27 publications

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

The effects of metformin and alendronate in attenuating bone loss and improving glucose metabolism in diabetes mellitus mice

The Future of Metformin in the Prevention of Diabetes-Related Osteoporosis

The Function of Metformin in Aging-Related Musculoskeletal Disorders

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