Fibroblast Growth Factor 21 Is Associated With Bone Mineral Density, but not With Bone Turnover Markers and Fractures in Chinese Postmenopausal Women

He, Jia; Fu, Wen‐Zhen; Wang, Chun; Yue, Hue; Gu, Juan; Zhang, Hao; Zhang, Zhenlin

doi:10.1016/j.jocd.2018.08.005

Cited by 14 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in that study, BMD at the femoral neck was negatively associated with the FGF21 concentration, even after adjusting for age and sex. In contrast to our study, the FGF21 concentration was positively correlated with BMD at the spine in healthy younger women (∼34 years old; Lee et al., 2013) and in postmenopausal women (∼69 years old) with fragility fractures (Hu et al., 2019), even after adjusting for age. In contrast, no association was found between the FGF21 concentration and BMD at the spine, hip or femoral neck in postmenopausal women aged ∼60 years (Choi, Lee, Kim, & Cho, 2018).…”

Section: Discussioncontrasting

confidence: 99%

“…This participant profile differed from earlier studies that were conducted on healthy participants without medications (Lee et al., 2013) or without chronic diseases (Hao et al., 2018) and women with fragility fractures (Hu et al., 2019). The lack of agreement in results could be attributable to differences in lifestyle or samples tested and the inclusion of both sexes in our study, which differed from earlier studies that included only younger (Lee et al., 2013) and older women (Choi et al., 2018; Hu et al., 2019). The independent and opposing associations of age with the higher FGF21 concentration and lower BMD could have contributed to the attenuation of the correlation observed between FGF21 and BMD at the lumbar spine in our study.…”

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

Age‐related bone loss is associated with FGF21 but not IGFBP1 in healthy adults

Lee

Fam

Chia

et al. 2020

Experimental Physiology

View full text Add to dashboard Cite

Bone fragility increases with age. The fibroblast growth factor 21 (FGF21)-insulin-like growth factor binding protein 1 (IGFBP1) axis regulates bone loss in animals. However, the role of FGF21 in mediating age-associated bone fragility in humans remains unknown. The purpose of this study was to explore the FGF21-regulatory axis in bone turnover and the age-related decline in bone mineral density (BMD). Twenty 'genetically linked' family (parent and child) pairs were recruited. Younger adults were 22-39 years old and older adults 60-71 years old. The BMD and serum concentrations of FGF21, IGFBP1, receptor activator of nuclear factor-B ligand (RANKL), tartrate-resistant acid phosphatase 5b (TRAP5b) and bone-specific alkaline phosphatase (BAP) were measured. Older adults had 10-18% lower BMD at the hip and spine (P < 0.008) and a twofold higher FGF21 concentration (P < 0.001). The IGFBP1 concentration was similar in younger and older adults (P = 0.961). The RANKL concentration was 44% lower (P = 0.006), whereas TRAP5b and BAP concentrations were 36 and 31% higher (P = 0.01 and P = 0.004), respectively, in older adults than in younger adults. Adjusting for sex did not affect these results. The FGF21 concentration was negatively correlated with BMD at the spine (r = −0.460, P = 0.003), but not with the IGFBP1 concentration (r = −0.144, P = 0.374).The IGFBP1 concentration was not correlated with BMD at the hip or spine (all P > 0.05).In humans, FGF21 might be involved in the age-associated decline in BMD, especially at the spine, through increased bone turnover. IGFBP1 is unlikely to be the downstream effector of FGF21 in driving the age-associated decline in BMD and in RANKL-associated osteoclast differentiation.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 68%

Age‐related bone loss is associated with FGF21 but not IGFBP1 in healthy adults

Lee

Fam

Chia

et al. 2020

Experimental Physiology

View full text Add to dashboard Cite

show abstract

“…However, others did not detect bone loss in rhFGF‐21–treated or AAV8‐hAAT‐FGF‐21 genetically engineered high‐fat diet–induced obesity mice, in high‐fat–fed obese monkeys and minipigs; and FGF‐21 knockout mice did not show high bone mass phenotype . An independent positive association between plasma FGF‐21 levels and BMD in 24 healthy young women and in postmenopausal women were also reported. Overall, the role of FGF‐21 on bone homeostasis remains controversial.…”

Section: Discussionmentioning

confidence: 98%

Increased Expression of FGF-21 Negatively Affects Bone Homeostasis in Dystrophin/Utrophin Double Knockout Mice

Sun

Qian

et al. 2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy seen in children. In addition to skeletal muscle, DMD also has a significant impact on bone. The pathogenesis of bone abnormalities in DMD is still unknown. Recently, we have identified a novel bone‐regulating cytokine, fibroblast growth factor‐21 (FGF‐21), which is dramatically upregulated in skeletal muscles from DMD animal models. We hypothesize that muscle‐derived FGF‐21 negatively affects bone homeostasis in DMD. Dystrophin/utrophin double‐knockout (dKO) mice were used in this study. We found that the levels of circulating FGF‐21 were significantly higher in dKO mice than in age‐matched WT controls. Further tests on FGF‐21 expressing tissues revealed that both FGF‐21 mRNA and protein expression were dramatically upregulated in dystrophic skeletal muscles, whereas FGF‐21 mRNA expression was downregulated in liver and white adipose tissue (WAT) compared to WT controls. Neutralization of circulating FGF‐21 by i.p. injection of anti‐FGF‐21 antibody significantly alleviated progressive bone loss in weight‐bearing (vertebra, femur, and tibia) and non–weight bearing bones (parietal bones) in dKO mice. We also found that FGF‐21 directly promoted RANKL‐induced osteoclastogenesis from bone marrow macrophages (BMMs), as well as promoted adipogenesis while concomitantly inhibiting osteogenesis of bone marrow mesenchymal stem cells (BMMSCs). Furthermore, fibroblast growth factor receptors (FGFRs) and co‐receptor β‐klotho (KLB) were expressed in bone cells (BMM‐derived osteoclasts and BMMSCs) and bone tissues. KLB knockdown by small interfering RNAs (siRNAs) significantly inhibited the effects of FGF21 on osteoclast formation of BMMs and on adipogenic differentiation of BMMSCs, indicating that FGF‐21 may directly affect dystrophic bone via the FGFRs‐β‐klotho complex. In conclusion, this study shows that dystrophic skeletal muscles express and secrete significant levels of FGF‐21, which negatively regulates bone homeostasis and represents an important pathological factor for the development of bone abnormalities in DMD. The current study highlights the importance of muscle/bone cross‐talk via muscle‐derived factors (myokines) in the pathogenesis of bone abnormalities in DMD. © 2019 American Society for Bone and Mineral Research.

show abstract

“… 108 Serum FGF21 concentration is positively correlated with lumbar BMD. 173 FGF21 can lead to growth attenuation by antagonizing the stimulatory effects of growth hormone and even directly suppress the proliferation and differentiation of chondrocytes in the growth plate. 174 FGF21 can enhance the osteogenic effect of BMP2.…”

Section: Fgf Signaling In Skeleton Development and Repair/regeneratiomentioning

confidence: 99%

FGF/FGFR signaling in health and disease

Xie

Yang

et al. 2020

Sig Transduct Target Ther

449

391

View full text Add to dashboard Cite

Growing evidences suggest that the fibroblast growth factor/FGF receptor (FGF/FGFR) signaling has crucial roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, differentiation, proliferation, and apoptosis of various types of cells. In this review, we provide a comprehensive overview of the current understanding of FGF signaling and its roles in organ development, injury repair, and the pathophysiology of spectrum of diseases, which is a consequence of FGF signaling dysregulation, including cancers and chronic kidney disease (CKD). In this context, the agonists and antagonists for FGF-FGFRs might have therapeutic benefits in multiple systems.

show abstract

Fibroblast Growth Factor 21 Is Associated With Bone Mineral Density, but not With Bone Turnover Markers and Fractures in Chinese Postmenopausal Women

Cited by 14 publications

References 30 publications

Age‐related bone loss is associated with FGF21 but not IGFBP1 in healthy adults

Age‐related bone loss is associated with FGF21 but not IGFBP1 in healthy adults

Increased Expression of FGF-21 Negatively Affects Bone Homeostasis in Dystrophin/Utrophin Double Knockout Mice

FGF/FGFR signaling in health and disease

Contact Info

Product

Resources

About