Table 1.
Overview of studies that have identified cell-free microRNAs (c-miRs) as biomarkers to distinguish osteoporosis/osteopenia (OP/Ope) patients from normal bone mineral density (BMD) without fragility fracture (woF) subjects.
| Study Design | OP Diagnosis | c-miR Source | Platforms for c-miR Quantification | Validate c-miR Biomarkers |
Normalization Strategy | AUC Value | c-miR Correlations |
Ref | |
|---|---|---|---|---|---|---|---|---|---|
| Prescreening | Validation | ||||||||
| PM: OP (40), Ope (40), CTR (40) | DXA | Plasma | / | qPCR | miR-21-5p (↓), miR-133a (↑), in OP and Ope vs. CTR | miR-16 | / | miR-21-5p and miR-133a/h- and BMD (+) and (−) respectively | [25] |
| PM: OP (10), Ope (7) CTR (19) | DXA | Serum | Microarray | qPCR | miR-30-5p (↓) in OP and Ope vs. CTR; miR-328a-3p, miR-103-3p and miR-142-3p (↓) in OP vs. CTR | miR-25-3p | miR-30-5p: 0.79; miR-328a-3p: 0.87; miR-103-3p: 0.8; miR-142-3p: 0.79 | All four miRs/BMD (+) | [26] |
| PM: OP (17), CTR (57) | DXA FRAX | Plasma | / | qPCR | miR-148-3p (↑) in OP vs. CTR | let-7a-5p and miR-16-5p | / | miR-126-3p/BMD (+); miR-423-5p/FRAX (−) | [27] |
| PM OP (20), PRM CTR (20), PM CTR (20) | DXA | Serum | Microarray | qPCR | miR-96 (↑) in OP vs. PM CTR and (↓) in OP vs. PRM CTR | U6 | / | miR-96/BALP (−) | [28] |
| OP (9), CTR (9) | DXA | Serum | Microarray | qPCR | miR-10b-3p and miR-100 (↑), and miR-328-3p and let-7g-5p (↓) in OP vs. CTR | U6 | miR-10b-3p: 0.87 | / | [29] |
| OP (60), CTR (60)/OP (60), CTR (40) | QCT | Serum | / | qPCR | miR-203 (↓) in OP vs. CTR | / | / | / | [30,31] |
| PM: LBMD (109), CTR (41) | DXA | Plasma | / | qPCR | miR-21-5p (↑) in LBMD vs. CTR | cel-miR-39 | / | miR-21-5p/BMD (−) | [32] |
| PM: LBMD (46), CTR (13) | DXA | Serum | / | qPCR | miR-21-5p, miR-23a-3p (↑), and miR- 125b-5p (↓) in LBMD vs. CTR | miR-16-5p, miR-93-5p, miR-191-5p | / | miR-21-5p and miR-133a-3p/BMD (−) and (+), respectively; miR-23a-3p/TRAP5b (+) | [33] |
| OP (48), CTR (48) | / | Serum | / | qPCR | miR-17, miR-20a, miR-21 and miR-29a (↓) in OP vs. CTR | U6 | / | / | [34] |
| OP (/), CTR (/) | / | Serum | / | qPCR | miR-579-3p (↑) in OP vs. CTR | U6 | / | / | [35] |
| PM: OP (20), CTR (20) | μCT | Serum | / | qPCR | miR-28, miR-101 and miR-373 (↓) in OP vs. CTR | U6 | / | / | [36] |
| OP (/), CTR (/) | / | Serum | / | qPCR | miR-30a-5p (↑) in OP vs. CTR | / | / | / | [37] |
| PM: OP (26), CTR (29) | / | Serum | / | qPCR | miR-410 (↑) in OP vs. CTR | U6 | / | / | [38] |
| PM: OP (15), CTR (15) | / | Serum | / | qPCR | miR-144 (↑) in OP vs. CTR | U6 | / | miR-144/Sfrp1 (+) | [39] |
| OP (30), CTR (30) | / | Serum | / | qPCR | miR-200a-3p (↑) in OP vs. CTR | U6 | / | / | [40] |
| PM: OP (15), CTR (15) | / | Serum | / | qPCR | miR-338-3p and miR-3065-5p (↑) in OP vs. CTR | U6 | miR-338-3p: 0.74; miR-3065-5p: 0.87 | / | [41] |
| OP (42), CTR (42) | / | Serum | / | qPCR | miR-19a-3p (↓) in OP vs. CTR | U6 | / | / | [42] |
| OP (60), CTR (60) | DXA | Serum | / | qPCR | miR-21-5p (↑) in OP vs. CTR | / | / | miR-21-5p/RUNKL and OPG (+) | [43] |
| OP (120), CTR (120) | / | Plasma | / | qPCR | miR-100 (↑) in OP vs. CTR | / | miR-100: 0.89 | miR-100/BMD (−) | [44] |
| OP (30), CTR (30) | / | Serum | / | qPCR | miR-375 (↑) in OP vs. CTR | U6 | / | / | [45] |
| OP (30), CTR (30) | / | Serum | / | qPCR | miR-429 (↑) in OP vs. CTR | / | / | / | [46] |
| OP (/), CTR (/) | / | Serum | / | qPCR | miR-1286 (↑) in OP vs. CTR | / | / | / | [47] |
| OP (/), CTR (/) | / | Serum | / | qPCR | miR-217 (↑) in OP vs. CTR | / | / | / | [48] |
| PM+PRM OP (70), PM+PRM CTR (70) | DXA | Serum | / | qPCR | miR-208a-3p (↑) in OP vs. CTR; miR-155-5p and miR-637 (↑) in PM OP vs. PM CTR; miR-155-5p (↓) PRM OP vs. PRM CTR | SNORD68 | PM OP vs. PM CTR: miR-208a-3p: 0.82; miR-155-5p: 0.9; miR-637: 0.63. PM OP vs. PM CTR: miR-208a-3p: 0.85; miR-155-5p: 0.83; miR-637: 0.81. | All 3 miRs/BMD (−) | [49] |
| PM: LBMD (35), CTR (30) | DXA | Serum | / | qPCR | miR-124 and miR-2861 (↑) LBMD vs. CTR; miR-21-5p, miR-29a-3p, miR-23a-3p (↓) in LBMD vs. CTR | / | miR-21-5p: 0.66; miR-29a-3p: 0.61; miR23a-3p: 0.63 | / | [50] |
| OP (33), Ope (61), CTR (12) | DXA | Serum and plasma | qPCR array | qPCR | miR-122-5p (↓ in serum) OP vs. Ope, OP vs. N, Ope vs. N; miR-4516 (↓ in plasma) OP vs. N | SNORD96A, RNU6–6P | miR-122-5p: 0.67; miR-4516: 0.73; miR-122-5p+miR-4516: 0.75 | miR-122-5p and miR-4516/BMD (+) | [51] |
| PM OP (16), PM Ope (28), PM CTR (22) | DXA or fracture | Serum | miRtaqman array card | qPCR | miR-23b-3p and miR-140-3p (↑) in OP/ Ope vs. CTR; miR-885-5p (↑) in Ope vs. CTR | RNU6-1 | miR-140-3p: 0.96 for OP, 0.84 for Ope; miR-23b-3p: 0.69 for OP, 0.73 for Ope; miR-885-5p: 0.69 for Ope | miR-23b-3p and miR-140-3p/BMD (−) | [52] |
| OP (24), CTR (24) | DXA | Plasma | Microarray | qPCR | miR-19b-3p (↓) in OP vs. CTR | U6 | miR-19b-3p: 0.93 OP, | miR-19b-3p/BMD (+) | [53] |
| PM OP (81), PRM CTR (74) | DXA | Serum | Microarray | qPCR | miR-27a (↓) in OP vs. CTR | U6 | / | / | [55] |
| PM: OP (17), Ope (14), PRM CTR (14) | DXA | Serum | Microarray | qPCR | miR-204-3p (↑) in OP/Ope vs. CTR; miR-181c-5p and miR-497-5p (↓) in OP/Ope vs. CTR | 5S | miR-204-3p: 0.96, miR-181c-5p: 0.87 and miR-497-5p: 0.92 for OP; miR-204-3p: 0.77, miR-181c-5p: 0.69 and miR-497-5p: 0.75 for Ope; | miR-204-3p/BMD (−), BMI and CTx (+); miR-181c-5p and miR-497-5p/BMD (+) | [56] |
↑: up-regulated, ↓: down-regulated, +: positive correlation, −: negative correlation.