Table 1.
The association between FGF23 and bone mineral density and fragility fracture in elderly.
| Study Design | Key Findings | Interpretation | Ref. | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient Group | Age (Year) | Study Base | Serum FGF23 (pg./mL) | OB Activity/Proliferation |
OC Activity/Proliferation |
BMD/ Bone Architecture |
Fragility Fracture | ||
| Men (n = 2782) |
75.4 ± 3.1 | cross- sectional (Sweden) |
49 ± 40.8 E | N/A | N/A | ↔ BMD a (age, smoking, height, weight) | N/A | FGF23 weakly associated with BMD in elderly men, but there was not clinical and statistical significance after adjustment with potential confounders. | [2] |
| ↑ BMD a (Pi, Ca, PTH, eGFR, 25(OH)2D3) | |||||||||
| Men (n = 3014) |
75.4 ± 3.2 | prospective cohort |
ref. > 57.4 E (median) |
N/A | N/A | N/A | ↑ a (BMI, FN BMD, eFGR, Pi, PTH, 25(OH)2D3, other fracture risks) | High circulating FGF23 was an independent risk factor of overall fragility fracture in elderly men. | [29] |
| (Sweden) | |||||||||
| Men (n = 1680) eGFR > 60 |
73.7 ± 5.8 | prospective case-cohort (USA) |
22.4–111.1 I (quartile 4) |
N/A | N/A | ↔ BMD | ↔ a (FN BMD, Pi, PTH, 25(OH)2D3, other fracture risks) | There was no significant association between BMD or osteoporosis fracture with FGF23 in elderly men who had eFGR > 60. |
[28] |
| Men (n = 997) |
75.3 ± 3.2 | cross- sectional |
42.2 (20.6) I | N/A | N/A | ↑ LS BMD a (age, BMI, cysC, Pi, PTH, 25(OH)2D3, Apo-B/A1 ratio, Iron study) | N/A | Increasing serum FGF23 level in elderly men was weakly associated with lumbar BMD. | [30] |
| (Sweden) | |||||||||
| pre- menopause (n = 60) |
43.8 ± 5.3 | cross- sectional (China) |
44.5 ± 9.2 E | ref. | ref. | ref. | N/A | In early post-menopause, estrogen deprivation caused BMD reduction from excessive bone resorption and decreased bone formation. Increased FGF23 might be a compensational response to this process. In post-menopausal women with low bone mass, increasing FGF23 showed a strong negative correlation with BMD. |
[1] |
| early menopause (n = 60) |
48.6 ± 4.7 | 76.7 ± 11.6 E | ↓ OC ↑↑P1NP |
↑ CTX-1 | ↓ PF BMD ↓ LS BMD |
N/A | |||
| late menopause (n = 60) |
53.4 ± 3.2 | 29.2 ± 8.6 E | ↓ OC ↔P1NP |
↑ CTX-1 | ↓↓ PF BMD ↓↓ LS BMD |
N/A | |||
| post menopause with low bone mass (subgroups) | |||||||||
| PF t-score −1 to −2 |
73.5 ± 9.6 E | N/A | N/A | ↓↓ PF BMD b | N/A | ||||
| PF t-score <−2 |
82.5 ± 8.4 E | ||||||||
| LS t-score −1 to −2 |
75.5 ± 9.7 E | N/A | N/A | ↓↓ LS BMD b | N/A | ||||
| LS t-score <−2 |
82.9 ± 9.1 E | ||||||||
| osteoporosis patient (n = 82) |
64.0 ± 12.7 | cross- sectional (Germany) |
98 ± 133 C | ↔ BALP | N/A | ↓ BV/TV a (age, BMI, Pi, PTH, 25(OH)2D3, BAP) | N/A | High FGF23 was associated with reduced trabecular bone micro-architecture in osteoporosis. | [3] |
| ↓↓ Tb.N a (age, BMI, Pi, PTH, 25(OH)2D3, BAP) | |||||||||
| ↓ Tb.Th a (age, BMI, Pi, PTH, 25(OH)2D3, BAP) | |||||||||
| All genders (n = 73) |
76.2 ± 8.0 | cross- sectional (Japan) |
37 (12.7) E | ↓ BALP b | ↓ P1NP b | ↔BMD b | N/A | FGF23 did not show a clinically significant association with BMD and bone remodeling when adjusted for confounders. | [31] |
| ↔ TRAP5b a (eGFR, 25(OH)2D3) | |||||||||
| post menopause (n = 55) |
61 ± 1.1 | cross- sectional (Romania) |
81.2 ± 3.6 C | N/A | ↔ CTX-1 b | ↓ FN BMD a (PTH, 25(OH)2D3, Leptin) | N/A | Serum FGF23 level was independently associated with decreasing BMD in the femoral neck in post- menopausal women. | [4] |
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 significant increased, ↑: significant increased, ↔: no significant difference, ↓: significant decrease, ↓↓: very significant decrease (within study comparison); Abbreviations: BALP, bone alkaline phosphatase; BMD, bone mineral density; BV/TV, bone volume/trabecular volume; CTX-1, serum c-telopeptide of type 1 collagen; FN, femoral neck, FT, Femoral trochanter; N/A, data not available; OC, serum osteocalcin; P1NP, serum propeptide of type 1 procollagen; PF, proximal femur, LS: lumbar spine; ref., reference (comparison group by univariate analysis), TH, total hip; Tb.N, trabecular number; Tb.Th, trabecular thickness; TRAP5b, serum tartrate-resistant acid phosphatase 5b.