Table 2.
The association between FGF23 and bone mineral density and fragility fracture in CKD and ESRD patients.
| Study Design | Key Findings | Interpretation | Ref. | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient Group | Age (Year) | Study-Based | Serum FGF23 (pg./mL) | OB Activity/Proliferation |
OC Activity/Proliferation |
BMD | Fragility Fracture |
||
| post menopause eGFR 45.7 ± 24.1 (n = 105) |
73.2 (7.7) | cross-sectional (Japan) |
49 (37) E ref. > 56.8 E |
N/A | ↔NTX a (age, BMI, eFGR, Ca, Pi, PTH, 1,25(OH)2D) | N/A | ↑ vertebral a (age, eGFR) | The higher level of FGF23 was associated with vertebral fracture in the elderly with CKD. There was no significant difference between FGF23 and osteogenic biomarkers. | [34] |
| men | 73.7 | prospective | 22.4–111.1 I | N/A | N/A | N/A | ↑↑ non-vertebral a (FN BMD, Pi, PTH, 25(OH)2D3, other fracture risks) | FGF23 elevation had increased the risk of non- vertebral fractures in the subgroup of elderly men with CKD (eFGR < 60). | [28] |
| eGFR < 60 | ± 5.8 | case-cohort | (quartile 4) | ||||||
| subgroup, (n = 313) | (USA) | ||||||||
| CKD 2–5 (n = 142) |
67 ± 12 | prospective cohort |
52.55 ± 55.19 E | N/A | N/A | ↔ b | N/A | Serum FGF23 level was not associated with BMD in CKD patients. | [46] |
| (France) | |||||||||
| ESRD with MHD | 60.6 ± 11.3 | cross- sectional |
N/A | N/A | N/A | ↔ b | N/A | No association between FGF23 and BMD in ESRD patients was found. FGF23 in ESRD patients with osteoporosis was significantly higher than patients without osteoporosis or osteopenia. |
[44] |
| (n = 64) | (China) | ||||||||
| Subgroup | |||||||||
| normal (n = 10) |
55.4 ± 5.0 | 218.7 ± 28.6 E | ref. | N/A | t-score > −1 | N/A | |||
| osteopenia (n = 24) |
64.4 ± 3.9 | 235.6 ± 54.4 E | ↑BALP | N/A | t-score −1 to −2.5 |
N/A | |||
| osteoporosis (n = 30) |
67.4 ± 3.8 | 296.2 ± 48.6 E | ↑↑BALP | N/A | t-score < −2.5 | N/A | |||
| KT (n = 106) eFGR |
40.1 ± 11.1 | cross- sectional |
25.29 ± 30.81 E | N/A | N/A | ↔ b | N/A | No relationship was found between FGF23 and BMD in KT and CKD patients. | [42] |
| 72.6 ± 27.1 | (Turkey) | ||||||||
| CKD (n = 30) eGFR 65.2 ± 54.6 |
39.2 ± 11.3 | 28.86 ± 26.5 E | N/A | N/A | ↔ b | N/A | |||
| post menopause (n = 102) |
prospective case-control (Greece) |
N/A | N/A | N/A | ↔ b | N/A | Elevated FGF23 was not associated with BMD in ESRD with HD. However, BMD was significantly decreased when compared with health matched controls. | [43] | |
| Subgroups | |||||||||
| ESRD with MHD (n = 50) | 62 ± 9.6 | 1027.8 ± 556.7 C | N/A | N/A | ↓ | N/A | |||
| healthy control (n = 52) |
59 ± 9.5 | 100.3 ± 54.7 C | N/A | N/A | ref. | N/A | |||
| ESRD with MHD (n = 130) |
72 (14) |
Prospective nested case-control (Canada) |
787 (1430) C |
↔ OC b ↔P1NP b |
↔ TRAP5b b ↔ Sclerostin b |
N/A | ↑ all fracture a (PTH, ferritin, smoking, P1NP) |
C-terminal FGF23 was associated with fracture incidence in ESRD with regular HD patients. There was no significant correlation between FGF23 and bone cell biomarkers. | [35] |
| ESRD with MHD | 53 ± 14.6 | cross- sectional |
221.9 ± 248.9 E | ↔BALP b | ↔CTX-1 b | ↔ b | ↔ | FGF23 was significantly increased in ESRD patients with lumbar spine osteo- porosis, but no correlation between BMD and FGF23 was observed. The biomarkers related to bone formation and resorption did not show any difference between normal bone, osteopenia and osteoporosis. |
[45] |
| (n = 90) | (Tunisia) | ||||||||
| Subgroups | |||||||||
| LS osteoporosis (n = 8) |
65.8 ± 10.1 | ↑ 428.1 ± 275.6 E | ↔ BALP | ↔ CTX-1 | ↔ b | N/A | |||
| vs. normal/ osteopenia (ref.) | |||||||||
| TH osteoporosis (n = 18) |
63.9 ± 11.4 | ↔ 250.3 ± 250.3 E | ↔ BALP | ↔ CTX-1 | ↔ b | N/A | |||
| vs. normal/ osteopenia (ref.) | |||||||||
a adjusted by multivariate analysis, b univariate correlation, C C-terminal fragment FGF23 (kRU/L) ELISA, E intact FGF23 two site monoclonal ELISA, I intact FGF23 polyclonal ELISA; Values are expressed as mean ± SD and median (IQR), ↑↑: very significantly increased, ↑: significantly increased, no significant difference, ↓: significantly decreased, ↓↓: very significantly decreased (within study comparison); Abbreviations: all fractures, (hip fractures, other fractures, and vertebral fractures); BMD, bone mineral density; BALP, bone alkaline phosphatase; CKD, chronic kidney disease; CTX-1, serum c-telopeptide of type 1 collagen; ESRD, end-stage renal disease; KT, kidney transplant; TH, total hip; LS, lumbar spine; MHD, maintenance hemodialysis; non-vertebral, hip fracture and other fractures; NTX, urine N-terminal telopeptide; N/A, data not available; OC, serum osteocalcin; P1NP, serum propeptide of type 1 procollagen; ref., reference (comparison group by univariate analysis); TRAP5b, serum tartrate-resistant acid phosphatase 5b.