High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis

Rupp, Tobias; Butscheidt, Sebastian; Vettorazzi, Eik; Oheim, Ralf; Barvencik, Florian; Amling, Michael; Rolvien, Tim

doi:10.1007/s00198-019-04996-7

Cited by 55 publications

(35 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BMD is a gross measure of bone health status and does not reflect the microarchitecture of the bone [27]. Rupp et al [4] found that high FGF23 levels were associated with impaired trabecular microarchitecture at the distal radius and tibia defined by bone volume, trabecular thickness, and number among subjects with osteoporosis. However, the association between FGF23 and cortical aspects (thickness and BMD) was not significant.…”

Section: Fibroblast Growth Factor-23mentioning

confidence: 99%

“…They provide a snapshot of the bone remodelling process, which is valuable in monitoring the progression of bone-related diseases and the efficacy of osteoporosis treatment [1,2]. However, traditional BTMs may not represent individual skeletal health status because multiple studies have reported the absence of a significant association between BTMs and bone mineral density (BMD) [3], even among patients with osteoporosis [4]. In addition, multiple studies show conflicting results in the use of BTMs for fracture risk assessment [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures

Ramli

Chin

2020

Diagnostics

View full text Add to dashboard Cite

Bone turnover markers (BTMs) derived from the secretory activities of osteoblasts and the matrix-degrading activities of osteoclasts are useful in monitoring the progression of osteoporosis and the efficacy of anti-osteoporotic treatment. However, the usefulness of BTMs in predicting osteoporosis remains elusive. Osteocytes play a central role in regulating bone formation and resorption. The proteins secreted by osteocytes, such as fibroblast growth factor-23 (FGF23), sclerostin (SOST), and dickkopf-1 (DKK1), could be candidates for osteoporosis screening and fracture prediction. This review summarizes the current evidence on the potential of osteocyte-related proteins as biomarkers for osteoporosis and fracture prediction. The literature reports that SOST may be a potential marker for osteoporosis screening but not for fracture prediction. FGF23 is a potential marker for increased fracture risk, but more studies are needed to confirm its usefulness. The role of DKK1 as a marker to predict osteoporosis and fracture risk cannot be confirmed due to a lack of consistent evidence. In conclusion, circulating osteocyte markers are potential osteoporosis biomarkers, but more studies are warranted to validate their clinical use.

show abstract

Section: Fibroblast Growth Factor-23mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures

Ramli

Chin

2020

Diagnostics

View full text Add to dashboard Cite

show abstract

“…We were intrigued by the paper of Rupp and coworkers; they showed that fibroblast growth factor 23 (FGF23) levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis, also after adjusting for confounding variables [1].…”

Section: Dear Editormentioning

confidence: 99%

FGF 23 and trabecular microarchitecture

et al. 2019

View full text Add to dashboard Cite

“…

…”

mentioning

confidence: 99%

“…We thank Dr. Minisola and coworkers for their interest in our article entitled "High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis" [1], in which we have outlined the significant association between high c-terminal FGF23 (cFGF23) and impaired bone microarchitecture.…”

mentioning

confidence: 99%

FGF23 and bone microarchitecture

2019

Self Cite

View full text Add to dashboard Cite

We thank Dr. Minisola and coworkers for their interest in our article entitled "High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis" [1], in which we have outlined the significant association between high c-terminal FGF23 (cFGF23) and impaired bone microarchitecture.Next to normal FGF23 levels in most of the included osteoporosis patients, we noticed moderately increased FGF23 levels in a number of patients without phosphate wasting. In fact, we treat several patients with confirmed tumor-induced osteomalacia (TIO) by 68 Ga DOTA-TATE PET/CT and very high FGF23 levels > 1000 kRUL/l in our department, but it is correct that there are other patients with TIO and only moderately increased or normal FGF23 levels [2]. While we had already excluded two patients with TIO in the initial phase of the study, we indeed included also osteoporosis patients with FGF23 values well above the specified reference range. In the patient with the highest FGF23 level, we repeatedly observed low phosphate values. Extended diagnostics including 68 Ga DOTA-TATE PET/CT and genetic screening for all known mutations leading to increased FGF23 levels (e.g., PHEX) were all inconspicuous. However, we are aware that these results do not necessarily exclude TIO. The patient with the second highest FGF23 level showed no laboratory signs of phosphate wasting.In accordance with the present commentary by Minisola et al., we have now performed the same statistical analyses after exclusion of these two patients with the highest FGF23 levels. All associations between cFGF23 and trabecular microarchitecture remained significant in both the correlation analysis and the multiple linear regression model, besides trabecular number at the distal tibia (correlation analysis: p = 0.114). Interestingly, the correlation analysis yielded an additional significant negative association between FGF23 and cortical BMD at the distal tibia (p = 0.047).It is still debated which FGF23 assay (especially cFGF23 vs. intact FGF23 (iFGF23)) is the most appropriate to detect certain disease states of phosphate metabolism. While iFGF23 appears to be more biologically relevant, it was found that cFGF23 assays showed lower intra-individual variation [3]. As we had recently identified cases, where iFGF23 had failed to identify patients clearly presenting with clinical and laboratory signs of phosphate wasting, we decided to perform this study using the cFGF23 assay. Nonetheless, iFGF23 measurements might be superior in other cases, and this needs to be explored further.Lastly, we appreciate the authors' similar view on the potential direct role of FGF23 in bone mineralization, which is indeed supported by previous mouse studies including those using Hyp and Npt2 −/− mice. Although there is certainly a high complexity underlying the pleiotropic actions of FGF23, there is evidence for a negative influence of FGF23 on mineralization, potentially explained by FGF23-mediated suppression of the tissue-nonspecific alkaline phospha...

show abstract

High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis

Cited by 55 publications

References 25 publications

A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures

A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures

FGF 23 and trabecular microarchitecture

FGF23 and bone microarchitecture

Contact Info

Product

Resources

About