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

Recent evidence has indicated that fibroblast growth factor 21 (FGF21) regulates longitudinal bone growth, with increased FGF21 levels leading to bone loss. The present study evaluated the relationship between bone mineral density (BMD) and serum FGF21 levels in patients undergoing hemodialysis (HD). We analyzed blood samples from 95 patients undergoing HD and measured BMD using dual-energy X-ray absorptiometry of the lumbar vertebrae (L2–L4). Serum FGF21 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit. Thirteen (11.6%) patients were found to have osteoporosis, 27 (28.4%) osteopenia, and 57 patients had normal BMD. Advanced age and decreased body mass index, height, body weight, waist circumference, and triglyceride level were associated with lower lumbar T-scores, as were increased alkaline phosphatase, urea reduction rate, fractional clearance index for urea, and FGF21 levels. Low log-FGF21, increased body mass index, increased pre-HD body weight, and increased logarithmically transformed triglycerides (log-TG) were found to be significantly and independently associated with lumbar BMD by multivariate forward stepwise linear regression analysis with adjustment for significant confounders. We conclude that high serum FGF21 level is negatively associated with BMD in patients undergoing HD.

Download Full-text

Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis

Clinical Kidney Journal ◽

10.1093/ckj/sfz034 ◽

2019 ◽

Vol 13 (1) ◽

pp. 75-84 ◽

Cited By ~ 3

Author(s):

Myles Wolf ◽

Geoffrey A Block ◽

Glenn M Chertow ◽

Kerry Cooper ◽

Bruno Fouqueray ◽

...

Keyword(s):

Growth Factor ◽

Bone Turnover ◽

Secondary Hyperparathyroidism ◽

Fibroblast Growth Factor ◽

Bone Turnover Markers ◽

Calcium Supplementation ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth ◽

Secondary Analyses ◽

Turnover Markers

Abstract Background Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown. Methods To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide. Results Etelcalcetide reduced FGF23 [median % change (quartile 1–quartile 3)] from baseline to the end of the trial significantly more than placebo [–56% (–85 to –7) versus +2% (–40 to +65); P < 0.001] and cinacalcet [–68% (–87 to –26) versus –41% (–76 to +25); P < 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide. Conclusion These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium.

Download Full-text