Serum levels of irisin in postmenopausal women with osteoporotic hip fractures

Li, Kai; Jing, Pengwei; Liu, Zehan; Wang, Ying; Han, Zhu; Wang, Youqiang; Zheng, Zhirui; Wu, Yue; Wang, Tong; Li, Yuhui; Zhang, Hongying; Wang, Lichun

doi:10.1016/j.cyto.2021.155708

Cited by 16 publications

(9 citation statements)

References 56 publications

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“…Our result showed that postmenopausal women with serum irisin levels were younger, and it was consistent with the bivariate analysis of a negative correlation between age and serum irisin level in this study and other studies performed on postmenopausal women (18,21). So serum irisin level decreases with aging in postmenopausal women.…”

Section: Discussionsupporting

confidence: 92%

“…We found that the serum irisin level had no difference in postmenopausal women with and without histories of falls and fractures (including VFs), no matter recent or distant events, which was quite different from previous studies. Former research showed that low serum irisin level was independently associated with fracture risks in postmenopausal women, including hip fractures, vertebral fragility fractures, and previous osteoporotic fractures (20,21,31). The difference between our study and these studies might be explained by different study designs, that was, previous studies were case-control studies, but this study was a post hoc analysis of a community epidemiological survey, so the study populations were not comparable.…”

Section: Discussionmentioning

confidence: 99%

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Serum Irisin level is associated with fall risk, muscle strength, and cortical porosity in postmenopausal women

Liang

Qi²,

Jiajue³

et al. 2023

Front. Endocrinol.

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BackgroundIrisin plays a role in bone-muscle crosstalk, but the relationship between the serum irisin level and bone microarchitecture remains unknown.ObjectiveThis study aimed to investigate the relationships between serum irisin level and fall risk, muscle strength, bone mineral density (BMD), and bone microarchitecture among Chinese postmenopausal women.MethodsIn all 138 postmenopausal women, handgrip strength, short physical performance battery (SPPB), and the timed up-and-go test were performed to evaluate muscle strength, physical performance, and fall risk, respectively. The serum irisin was measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed to acquire volumetric BMD and bone microarchitecture. Bivariate analysis was used to explore relationships between serum irisin level and muscle strength and HR-pQCT parameters. Univariate and multivariate linear regression analyses were performed to determine associations between serum irisin level and vBMD and cortical porosity (Ct.Po).ResultsAll participants had a median serum irisin level of 3.91 μg/ml. Participants with high fall risk had significantly lower serum irisin levels than those with low fall risk (2.22 μg/ml vs. 4.16 μg/ml, p=0.024). Irisin level was positively related to handgrip strength (rs=0.185, p=0.030) and SPPB performance. In univariate linear regression, serum irisin level was positively associated with cortical volumetric BMD (Ct.vBMD, radius: standardized β=0.184, p=0.031; tibia: standardized β=0.242, p=0.004), but it had no significant associations with Ct.vBMD after multivariate adjustment. After adjusting by age, height, serum sclerostin level, and body fat ratio, only Ct.Po at the distal radius had a significantly negative association with serum irisin level (standardized β=-0.276, p=0.003).ConclusionPostmenopausal women with lower serum irisin levels have a higher fall risk, weaker muscle strength, and higher cortical porosity. Moreover, serum irisin level has a positive association with Ct.vBMD, but it is affected by factors such as age.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Serum Irisin level is associated with fall risk, muscle strength, and cortical porosity in postmenopausal women

Liang

Qi²,

Jiajue³

et al. 2023

Front. Endocrinol.

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“…In a study of 160 elderly women with hip fractures occurring after minimal trauma and 160 aged-matched controls, low irisin concentrations were independently associated with an increased risk of femur fractures when adjusted for BMD or FRAX score [51]. Using a different methodological approach, Liu et al performed a cross-sectional case-control study in 215 post-menopausal women with hip fractures and 215 age-matched controls without fractures and reported lower serum irisin levels in women with fractures, while identifying irisin levels in the lowest third and fourth quartiles as being positively associated with a high risk of hip fractures and osteoporosis after adjusting for age, BMI, BMD, FRAX, and physical activity score [52]. In contrast, similar irisin levels were reported between women with incident hip fractures sampled right before fixation, and the controls were post-menopausal women with knee or hip osteoarthritis schedules for arthroplasty [53], while even higher irisin levels post-fracture were reported in a study prospectively evaluating 21 patients with low extremity fractures for 60 days [54].…”

Section: Irisin In Post-menopausal and Senile Osteoporosismentioning

confidence: 99%

Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature

Tsourdi

Anastasilakis

Hofbauer

et al. 2022

JCM

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Irisin is a hormone-like myokine produced by the skeletal muscle in response to exercise. Upon its release into the circulation, it is involved in the browning process and thermogenesis, but recent evidence indicates that this myokine could also regulate the functions of osteoblasts, osteoclasts, and osteocytes. Most human studies have reported that serum irisin levels decrease with age and in conditions involving bone diseases, including both primary and secondary osteoporosis. However, it should be emphasized that recent findings have called into question the importance of circulating irisin, as well as the validity and reproducibility of current methods of irisin measurement. In this review, we summarize data pertaining to the role of irisin in the bone homeostasis of healthy children and adults, as well as in the context of primary and secondary osteoporosis. Additional research is required to address methodological issues, and functional studies are required to clarify whether muscle and bone damage per se affect circulating levels of irisin or whether the modulation of this myokine is caused by the inherent mechanisms of underlying diseases, such as genetic or inflammatory causes. These investigations would shed further light on the effects of irisin on bone homeostasis and bone disease.

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“…A recent study showed that patients with T1DM have lower circulating levels of irisin compared to the healthy controls [ 21 ]. Similarly, postmenopausal women with osteoporotic hip fractures exhibited lower serum levels of irisin compared with normal control women [ 22 ]. The administration of FNDC5/irisin was considered a potential therapeutic approach to improve or treat osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

FNDC5/irisin ameliorates bone loss of type 1 diabetes by suppressing endoplasmic reticulum stress‑mediated ferroptosis

Dong,

Han,

Gao

et al. 2024

J Orthop Surg Res

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Background Ferroptosis is known to play a crucial role in diabetic osteopathy. However, key genes and molecular mechanisms remain largely unclear. This study aimed to identify a crucial ferroptosis-related differentially expressed gene (FR-DEG) in diabetic osteopathy and investigate its potential mechanism. Methods We identified fibronectin type III domain-containing protein 5 (FNDC5)/irisin as an essential FR-DEG in diabetic osteopathy using the Ferroptosis Database (FerrDb) and GSE189112 dataset. Initially, a diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ), followed by intraperitoneal injection of irisin. MC3T3-E1 cells treated with high glucose (HG) were used as an in vitro model. FNDC5 overexpression plasmid was used to explore underlying mechanisms in vitro experiments. Femurs were collected for micro-CT scan, histomorphometry, and immunohistochemical analysis. Peripheral serum was collected for ELISA analysis. Cell viability was assessed using a CCK-8 kit. The levels of glutathione (GSH), malondialdehyde (MDA), iron, reactive oxygen species (ROS), and lipid ROS were detected by the corresponding kits. Mitochondria ultrastructure was observed through transmission electron microscopy (TEM). Finally, mRNA and protein expressions were examined by quantitative real‐time PCR (qRT‐PCR) and western blot analysis. Results The expression of FNDC5 was found to be significantly decreased in both in vivo and in vitro models. Treatment with irisin significantly suppressed ferroptosis and improved bone loss. This was demonstrated by reduced lipid peroxidation and iron overload, increased antioxidant capability, as well as the inhibition of the ferroptosis pathway in bone tissues. Furthermore, in vitro studies demonstrated that FNDC5 overexpression significantly improved HG-induced ferroptosis and promoted osteogenesis. Mechanistic investigations revealed that FNDC5 overexpression mitigated ferroptosis in osteoblasts by inhibiting the eukaryotic initiation factor 2 alpha (eIF2α)/activated transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) pathway. Conclusions Collectively, our study uncovered the important role of FNDC5/irisin in regulating ferroptosis of diabetic osteopathy, which might be a potential therapeutic target.

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Serum levels of irisin in postmenopausal women with osteoporotic hip fractures

Cited by 16 publications

References 56 publications

Serum Irisin level is associated with fall risk, muscle strength, and cortical porosity in postmenopausal women

Serum Irisin level is associated with fall risk, muscle strength, and cortical porosity in postmenopausal women

Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature

FNDC5/irisin ameliorates bone loss of type 1 diabetes by suppressing endoplasmic reticulum stress‑mediated ferroptosis

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