Table 4.
Methodology of studies on osteoporosis.
| Ref. | miR | miR Assay | Tissue | Endogenous Control | Technical Replicates | Timing of Sample Collection | miR Direction | Main Results |
|---|---|---|---|---|---|---|---|---|
| Al-Rawaf 2021 [26] | miR-148a and miR-122-5p | qRT-PCR | Serum | NR | Triplicate | In the morning, in fasted state | ↑ miR-148a ↓ miR-122-5p |
↑ miR-148a and ↓ miR-122-5p significantly associated with bone loss or osteoporosis in elderly postmenopausal women |
| Baloun 2022 [27] | let-7b-5p, miR-320a, miR-375, miR-188-5p, miR-152-3p, miR-582-5p, miR-144-5p, miR-141-3p, miR-127-3p, miR-17-5p | qRT-PCR | Serum | NR | NR | Before oophorectomy/ hysterectomy 201 ± 24 days after surgery 508 ± 127 days after Oophorectomy/hysterectomy 203 ± 71 days after estradiol treatment |
No differences | No association of miRs with osteoporosis |
| Bedene 2016 [28] | let-7d-5p, let-7e-5p, miR-30d-5p, miR-30e-5p, miR-126-3p, miR-148a-3p, miR-199a-3p, miR-423-5p, and miR-574-5p | qRT-PCR | Serum | NR | NR | NR | ↑ miR-148a-3p | miR-148a-3p as a potential plasma-based biomarker for osteoporosis |
| Chen 2016 [29] | miR-30a-5p, miR-30e-5p, miR-425-5p, miR-142-3p, miR-191a-3p, miR-215, miR-29b-3p, miR-30b-5p, miR-26a-5p, miR-345-5p, miR-361-5p, miR-185-5p, miR-103-3p | qRT-PCR | Serum | NR | NR | NR | ↓ miR-30b-5p in osteopenia/osteoporosis; ↓ miR-103-3p, miR-142-3p, miR-328-3p in osteoporosis |
miR-30b-5p down regulated in postmenopausal women with osteopenia or osteoporosis; ↓miR-103-3p, miR-142-3p, miR-328-3p only in osteoporosis |
| Chen 2017 [30] | miR-30, miR-96, miR-125b, miR-4665-3p, miR-5914 | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-125b, miR-30, and miR-5914 | miR-125b significantly upregulated in postmenopausal osteoporosis |
| Chen 2019 [31] | miR-19a-3p | qRT-PCR | Serum | U6 | NR | In the morning, in fasted state | ↓miR-19a-3p | miR-19a-3p down-regulated in osteoporosis |
| Chen 2019 b [32] |
miR-1-3p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-100-5p, miR-125b-5p, miR-133a-3p, miR-206 | qRT-PCR | Serum | miR-16-5p, -93-5p, and -191-5p |
NR | In the morning, in fasted state | ↓ miR-125b-5p and ↑ miR-21-5p and -23a-3 in osteoporosis | Relative expression level of miR-21-5p significantly negatively correlated with trochanter bone mineral content. |
| Cheng 2019 [33] | miR-365a-3p | qRT-PCR | Serum | NR | NR | In the morning, in fasted state | ↑miR-365a-3p | miR-365a-3p highly expressed in osteoporosis |
| Ciuffi 2022 [34] | miR-8085, miR-320a-3p, miR-23a-3p, miR-4497, miR-145-5p | ddPCR | Serum | Synthetic RNA spike-ins, UniSp2, UniSp4, and UniSp5 |
NR | NR | ↓ miR-23a-3p ↑ miR-320a-3p |
Levels of miR-23a-3p and miR-21-5p able to distinguish osteoporotic patients and subjects with normal BMD |
| Ding 2019 [35] | miR-100 | qRT-PCR | Serum | NR | NR | NR | ↑ miR-100 | miR-100 as potential biomarker for the diagnosis and treatment osteoporosis |
| Feurer 2019 [36] | miR-133a-3p, miR-20a-5p, miR-25-3p, miR-100-5p, miR-133b, miR-214-3p, miR-26a-5p, miR-103a-3p, miR-145-5p, miR-21-5p, miR-29a-3p, miR-106a-5p, miR-146a-5p, miR-221-5p, miR-29b-3p, miR-122-5p, miR-148a-3p, miR-222-3p, miR-338-3p, miR-124-3p, miR-155-5p, miR-223-5p, miR-34a-5p, miR-125b-5p, miR-17-5p, miR-23a-3p, miR-503-5p, miR-127-3p, miR-204-5p, miR-24-3p, miR-93-5p, miR-16-5p | qRT-PCR | Serum | UniSp6 | NR | In the morning, in fasted state | None | No significant association between prevalent or incident fractures, BTM, DXA, and HRpQCT parameters and analyzed miR |
| Fu 2019 [37] | miR-27a-3p | qRT-PCR | Serum | NR | NR | NR | ↓ miR-27a-3p | ↓miR-27a-3p in osteoporosis in comparison to controls |
| Fu 2021 [38] | miR-145-5p | qRT-PCR | Serum | U6 | Triplicate | In the morning, in fasted state | ↑ miR-145-5p | ↑miR-145-5p in osteoporotic in comparison to control |
| Gao 2020 [39] | miR-217 | qRT-PCR | Serum | NR | NR | NR | ↑ miR-217 | Up-regulation of miR-217 in osteoporotic in comparison to controls |
| Guo 2022 [40] | miR-221-5p | qRT-PCR | Serum | U6 | NR | NR | ↓ miR-221-5p | Down-regulation of miR-221-5p in osteoporotic in comparison to controls |
| Ismail 2020 [41] | miR-208a-3p, miR-155-5p, miR-637 | qRT-PCR | Serum | Hs_Snord68_11 | Duplicate | For premenopausal women: during the early follicular phase, i.e., days 3–7 of the menstrual cycle | ↑ miR-208a-3p, ↓ miR-155-5p | miR-208a-3p significantly upregulated, miR-155-5p markedly down-regulated in the premenopausal patients compared to its respective controls |
| Li 2014 [42] | miR-21, miR-133a, miR-146a | qRT-PCR | Plasma | miR-16 | NR | In the morning, in fasted state | ↓ miR-21 ↑ miR-133a |
Downregulation of miR-21 and upregulation of miR-133a in osteoporosis and osteopenia patients versus controls |
| Li 2018 [43] | miR-133a | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-133a | miR-133a significantly upregulated and negatively correlated with lumbar spine BMD in post-menopausal osteoporotic women |
| Li 2020 [44] | miR-483-5p | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-483-5p | ↑ expression of miR-483–5p in osteoporotic patients |
| Lu 2021 [45] | miR-206 | qRT-PCR | Serum | U6 | NR | NR | ↓ miR-206 | ↓ miR-206 in osteoporotic patient group versus controls |
| Luo 2019 [46] | miR-579-3p | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-579-3p | ↑ miR-579-3p in osteoporotic patients than controls |
| Lv 2019 [47] | miR-200a-3p | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-200a-3p | ↑miR 200a-3p in osteoporotic patients relative to controls |
| Ma 2021 [48] | miR-181c-5p, miR-497-5p, miR-204-3p, miR-1290 | qRT-PCR | Serum | 5S rRNA | NR | In the morning, in fasted state | ↓ miR-181c-5p and miR-497-5p ↑ miR-204-3p |
miR-181c-5p and miR-497-5p involved in bone metabolism and associated with progressive bone loss due to osteoporosis |
| Ma 2022 [49] | miR-455–3p | qRT-PCR | Serum | U6 | NR | NR | ↓ miR-455–3p | ↓ miR-455–3p in osteoporosis and fragility fracture patients compared to controls |
| Mandourah 2018 [50] | 370 mature miRs | qRT-PCR | Plasma and serum | SNORD61, SNORD68, SNORD72, SNORD95, SNORD96A, and RNU6-6P |
NR | NR | ↓ miR122-5p and miR4516 | miR122-5p and miR4516 present at significantly different levels between non-osteoporotic control, osteopenia, and osteoporosis patients |
| Mi 2020 [51] | miR-194-5p | qRT-PCR | Serum | U6 | Triplicate | NR | ↑ miR-194-5p | ↑ miR-194-5p level linked to osteoporosis |
| Nakashima 2020 [52] | let7d, miR1, miR17, miR20a, miR21, miR27a, miR34a, miR92, miR103a, miR122, miR126, miR130a, miR133a, miR146, miR150, miR192, miR195, miR197, miR199, miR221, miR222, miR320 |
qRT-PCR | Serum | NR | NR | In the morning, in fasted state | ↓ miR195, ↑ miR150 and miR222 | ↓ miR195 in osteoporotic females, ↑ miR150 and miR222 in osteoporotic males |
| Nobrega 2020 [53] | miR-1-3p, miR-21-5p, miR-34a-5p, miR-92a-3p, miR-100-5p, miR-126-3p, miR-130a-3p, miR-146a-5p, miR-155-5p, and miR-221-3p | qRT-PCR | Whole blood | RNU43 | NR | In the morning, in fasted state | ↑ miR-34a-5p | ↑ miR-34a-5p among very old adults who display the lowest scores of BMD |
| Panach 2015 [54] | Serum/Plasma microRNA PCR Panel |
qRT-PCR | Serum | UniSP6 and cel-miR-39 | NR | NR | ↑ miR-122-5p, miR-125b-5p, and miR-21-5p | miR-122-5p, miR-125b-5p, and miR-21-5p upregulated biomarkers in bone fracture with respect to controls |
| Pertusa 2021 [55] | miR-497-5p, miR-155-5p, miR-423-5p, miR-365-3p | qRT-PCR | Serum | Cel-miR-39 | NR | NR | ↑ miR-497 and miR-423 ↓ miR-155 and miR-365 |
↑ miR-497 and miR-423 and ↓ miR-155 and miR-365 in osteoporotic than in control |
| Qiao 2019 [56] | miR-203 | qRT-PCR | Serum | NR | NR | In fasted state | ↓ miR-203 | ↓ miR-203 in patients with postmenopausal osteoporosis than in controls |
| Ramírez-Salazar 2019 [57] | miR-23b-3p, miR-140-3p, miR-885-5p | qRT-PCR | Serum | RNU6 | NR | NR | ↑ miR-140-3p and miR-23b-3p | miR-140-3p and miR-23b-3p as potential biomarkers candidates for osteoporosis |
| Salman 2021 [58] | miR-133a, miR-25 3p | qRT-PCR | Serum | RNU43 | NR | NR | ↑ miR-133a | miR-133a as biomarker for osteoporosis |
| Seeliger 2014 [59] | let-7a-5p, miR-1, miR-100-5p, miR-106b-5p, miR-10b-5p, miR-122-5p, miR-124-3p, miR-125b-5p, miR-126-3p, miR-133a, miR-133b, miR-134, miR-141-3p, miR-143-3p, miR-146a-5p, miR-150-5p, miR-155-5p, miR-17-5p/106a-5p, miR-17-3p, miR-18a-5p, miR-192-5p, miR-195-5p, miR-196a-5p, miR-19a-3p, miR-19b-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-203a, miR-205-5p, miR-208a, miR-20a-5p, miR-21-5p, miR-210, miR-214-3p, miR-215, miR-221-3p, miR-222-3p, miR-223-3p, miR-224-5p, miR-23a-3p, miR-25-3p | qRT-PCR | Serum | RNU6 | Duplicate | NR | ↑ miR-21, miR-23a, miR-24, miR-93, miR-100, miR-122a, miR-124a, miR-125b, miR-148a | miR-21, miR-23a, miR-24, miR-93, miR-100, miR-122a, miR-124a, miR-125b, and miR-148a significantly upregulated in the serum of patients with osteoporosis |
| Shuai 2020 [60] | miR-29b-3p, miR-30c-2-3p, miR-145-5p, miR-199a-5p, miR-301a-3p, miR-497-5p, miR-526b-5p, miR-550a-5p, miR-575, miR-654-5p, miR-877-3p, miR-1260b, miR-4769-3p, miR-15a-5p, miR-424-5p, miR-663a, miR-708-5p, miR-1246, miR-1299, miR-1323, miR-4447, miR-5685 | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-30c-2-3p, miR-497-5p, 550a-5p, miR-654-5p, miR-663a, miR-877-3p, miR-1299 ↓ miR-199a-5p, miR424-5p, miR-1260b |
miR-30c-2-3p, miR-199a-5p, miR424-5p, miR-497-5p, miR-550a-5p, miR-654-5p, miR-663a, miR-877-3p, miR-1260b, miR-1299 ere highly expressed in serum and differed significantly among osteopenic, osteoporotic, and healthy patients |
| Sun 2020a [61] | miR-19b | qRT-PCR | Serum | U6 | NR | In the morning, in fasted state | ↓ miR-19b | ↓ miR-19b in osteoporotic patients with vertebral compression fractures than that in controls |
| Sun 2020b [62] | miR-211 | qRT-PCR | Serum | NR | NR | NR | ↑ miR-211 | In the fracture group, miR-211 expression was significantly up-regulated compared with controls |
| Tang 2019 [63] | miR-144 | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-144 | Expression of miR-144 upregulated in osteoporotic patients compared with control |
| Wang 2018 [64] |
miR-7-5p miR-211-5p, miR-24-3p, miR-27a-3p, miR-100, miR-125b, miR-122a, miR-128, miR 145, miR-144-3p | qRT-PCR | Serum | NR | Triplicate | NR | ↑ miR-24-3p, 27a-3p, 100, 125b, 122a, 145 ↓ miR-144-3p |
Significant upregulation of miR-24-3p, 27a-3p, 100, 125b, 145, and 122a in osteoporosis compared to control. miR-144-3p downregulated in in osteoporosis compared to control |
| Weilner 2015 [65] | miR-10a-5p, miR-10b-5p, miR-133b, miR-22-3p, miR-328-3p, let-7g-5p | qRT-PCR | Serum | U6 and 5S rRNA | NR | Between 8:00 a.m. and 10:00 a.m. in fasted state | ↑ miR-22-3p, ↓ miR-328-3p and let-7g-5p | De-regulation of miR-22-3p, miR-328-3p, and let-7g-5p in osteoporotic fractured patients |
| Wu 2021 [66] | miR-10a-3p | qRT-PCR | Serum | U6 | Triplicate | NR | ↑ miR-10a-3p | ↑ miR-10a-3p in osteoporotic patients |
| Xia 2018 [67] | miR-203 | qRT-PCR | Serum | NR | Triplicate | In the morning, in fasted state | ↓ miR-203 | ↓ miR-203 in osteoporosis patients that in controls |
| Xu 2022 [68] | miR-491-5p, miR-485-3p | qRT-PCR | Plasma | U6 | NR | NR | ↓ miR-491-5p and miR-485-3p | Expression levels of miR-491-5p and miR-485-3p declined in osteoporotic patients with vertebral fractures when compared to those without fractures |
| Yang 2019 [69] | miR-217 | qRT-PCR | Serum | NR | NR | In the morning, in fasted state | ↑ miR-217 | ↑ miR-217 in osteoporotic patients |
| Yavropoulou 2017 [70] | miR-21-5p, miR-23a-3p, miR-24-2-5p, miR-26a-5p, miR-29a, miR-33a-5p, miR-124-3p, miR-135b-5p, miR-214-3p, miR-218-5p, miR-335-3p, miR-2861 | qRT-PCR | Serum | RNU6-2 | Triplicate | NR | ↑ miR-124 and miR-2861; ↓ miR-21, miR-23, miR-29, miR-21-5p | miR-21-5p, miR-23a, miR-29a-3p, miR-124-3p, and miR-2861 significantly deregulated in osteoporotic compared with controls. ↑ miR-124 and miR-2861 and ↓ miR-21, miR-23 and miR-29 in osteoporotic compared with controls. ↓miR-21-5p in osteoporotic/osteopenic women with vertebral fractures |
| Yin 2022 [71] | miR-215-5p | qRT-PCR | Serum | U6 | Triplicate | In fasted state | ↓ miR-215-5p | ↓ miR-215-5p in patients with osteoporosis |
| You 2016 [72] | miR-27a | qRT-PCR | Serum | U6 | Triplicate | NR | ↓ miR-27a | miR-27a significantly down-regulated in postmenopausal osteoporotic patients |
| Yu 2020 [73] | miR-137 | qRT-PCR | Serum | U6 | NR | NR | ↑ miR-137 | ↑ miR-137 in osteoporotic in comparison to controls |
| Yuan 2021 [74] | miR-26a | qRT-PCR | Serum | NR | NR | NR | ↑ miR-26a | ↑ miR-26a in patients with osteoporosis |
| Zarecki 2020 [75] | miR-19b-3p miR-486-3p, miR-550a-3p, miR-106b-5p, miR-144-3p, miR-451a, miR-29b-3p, miR-96-5p, miR-188-5p, miR-532-3p, miR-30e-5p, miR-214-3p, miR-143-3p, miR-133b, miR-21-5p, miR-23a-3p, miR-152-3p, miR-335-5p, miR-127-3p, miR-375 |
qRT-PCR | Serum | cel-miR-39-3p | NR | After an overnight fast | ↑ miR-375, miR-532-3p, miR-19b-3p, miR-152-3p, miR-23a-3p, miR-335-5p, miR-21-5p | Up-regulated miR-375, miR-532-3p, miR-19b-3p, miR-152-3p, miR-23a-3p, miR-335-5p, miR-21-5p in patients with vertebral fractures and osteoporosis compared to osteoporosis without fracture and controls |
| Zhang 2019 [76] | miR-30a-5p | qRT-PCR | Serum | NR | NR | NR | ↑ miR-30a-5p | miR-30a-5p significantly upregulated in osteoporosis patients |
| Zhang 2021 [77] | miR-502-3p | qRT-PCR | Serum | U6 | Three duplicates | NR | ↓ miR-502-3p | ↓ miR-502-3p in osteoporotic than in controls |
| Zhao 2019 [78] | miR-17, miR-20a, miR-21, miR-26a, miR-29b, and miR-106b |
qRT-PCR | Serum | U6 | NR | NR | ↓ miR-21 | ↓ miR-21 expression in patients with osteoporosis than in controls |
| Zhou 2019 [79] | miR-let-7c | qRT-PCR | Serum | NR | Triplicate | NR | ↑ miR-let-7c | miR-let-7c up-regulated in patients with postmenopausal osteoporosis compared with controls |
↑: increase; and ↓: decrease.