Chinese Medical Sciences Journal ›› 2021, Vol. 36 ›› Issue (2): 135-149.doi: 10.24920/003729
刘婕妤1,2,3,王嘉祥1,2,3,许力1,2,邓飞艳1,2,*()
收稿日期:
2020-09-13
出版日期:
2021-06-30
通讯作者:
邓飞艳
E-mail:fdeng@suda.edu.cn
Jieyu Liu1,2,3,Jiaxiang Wang1,2,3,Li Xu1,2,Feiyan Deng1,2,*()
Received:
2020-09-13
Published:
2021-06-30
Contact:
Feiyan Deng
E-mail:fdeng@suda.edu.cn
摘要:
骨质疏松症是一种系统性的慢性骨骼疾病,其特征为骨矿密度低、骨质疏松性骨折风险升高。骨质疏松症好发于中老年人群,尤其是绝经后妇女。伴随着人口老龄化,骨质疏松症已成为全球范围内严重的公共卫生问题。尽早识别高危人群、及时有效的干预和治疗对于预防骨质疏松性骨折至关重要。鉴于骨质疏松症的遗传率较高且发病机制复杂,有必要综合考虑重要的生物分子、从而对骨质疏松性骨折进行准确的风险评估。为此,我们总结回顾了可用于骨质疏松性骨折风险评估的潜在生物分子及其最新研究进展。未来对于这些生物分子的系统评估有助于研发新的方法和检测策略,比如开发生物芯片,以应用于骨质疏松症的早期识别和骨质疏松性骨折的预防。
Jieyu Liu, Jiaxiang Wang, Li Xu, Feiyan Deng. Potential Biomolecules Capable of Assessing Risk of Osteoporotic Fracture: A Scoping Review[J].Chinese Medical Sciences Journal, 2021, 36(2): 135-149.
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Molecules | References | Sample size | Gender | Ethnicity | Age (yrs) (mean ±SD or range) | Follow-up (yrs) | Phenotype | Concentration | Effect size or difference | |
---|---|---|---|---|---|---|---|---|---|---|
Male | Female | |||||||||
IGFBP-I | Lundin et al.[ | 351 | Female | Sweden | 72.8±2.31 | 10 | OF | NA | NA | HF: Adj. HR=1.46, 95%CI(1.08-1.99) per SD increase; MOF: Adj.HR=1.33, 95%CI(1.05-1.69, P=0.017) |
Periostin | Rousseauet al.[ | 607 (women with incident fracture: 75 vs. women without incident fracture: 532) | Female | French | 66.6±8.4 | 7 | VF | 1249±340vs. 1162±298 ng/ml | NA | RR=2.81, 95%CI(1.1-7.3), P=0.03; Adj. RR=1.88, 95%CI(1.1-3.2) |
K-Postn | Bonnetet al.[ | 695 (fracture: 66 vs. no fracture: 629) | Female | Geneva | 65.0±1.5 | (mean±SD) 4.7±1.9 | Low-trauma clinical fracture | 57.5±36.6vs. 42.5±23.4 ng/ml | NA | HR=2.14, 95%CI(1.54-2.97), P<0.001 |
Adiponectin | Johansson et al.[ | 999 (fracture: 150 vs. no fracture: 849) | Male | Swedish | NA | (mean) 5.2 | OF | 14.2±8.9vs. 11.5±5.8 µg/ml | HR/SD=1.46, 95%CI (1.23-1.72) | NA |
Adiponectin | Johansson et al.[ | 989 (fracture: 124 vs. no fracture: 865) | Male | Swedish | 70-81 | (mean) 5.3 | OF | 14.4±9.3vs. 11.5±5.8 µg/ml | Adj. for age and time since baseline HR=1.47, 95%CI(1.23-1.77) per SD; Adj. for FN BMD and age HR=1.40, 95%CI(1.16-1.68) per SD | NA |
CRP | Oei et al.[ | 6386 | 59% female | Rotterdam | 69.1±8.9 | (mean) 11.6 | OF | NA | OF: HR=1.06, 95%CI(1.02-1.11) HF: HR=1.09, 95%CI(1.02-1.17) VF: OR=1.34, 95%CI(1.14-1.58) | |
BAP | Tamaki et al.[ | 522 | Female | Japanese | 54.7 (YSM<5 years); 66.6 (YSM≥5 years) | (median) 10 | VF | NA | NA | YSM<5 years:RR=4.38, 95%CI(1.45-13.21); YSM≥5 years:RR=1.39, 95%CI (1.12-1.74) |
FGF23 | Mirza et al.[ | 2868 | Male | Swedish | 75.4±3.2 | (median) 3.35 | OF/VF | NA | OF: HR=1.20, 95%CI(1.03-1.40); VF: HR=1.33, 95%CI(1.02-1.75); Above 55.7 pg/ml: HF: HR=2.30, 95%CI(1.16-4.58); non-VF: HR=1.63, 95%CI(1.01-2.63) | NA |
FGF23 | Lane et al.[ | 1680 (*Q1: 346; *Q2: 346; *Q3: 345; *Q4: 347) | Male | Swedish | Q1:73.40±5.8; Q2:73.63±5.91; Q3:74.40±6.0; Q4:73.70±5.8 | 5.3 | Non-spine OF | Q1-Q3: 4.2-22.4 pg/ml; vs. Q4: 22.4-111.1 pg/ml | RH=2.02, 95%CI(1.07-3.79) in men with eGFRCrCys <60 ml/min·1.73 m 2 | NA |
Sclerostin | Szulc et al.[ | 710 (fracture: 75 vs. no fracture: 635) | Male | French | 65±7 | 10 | OF | 0.54 (0.47, 0.64) vs. 0.61 (0.49, 0.77) ng/ml | All fracture: HR=0.55, 95%CI(0.31-0.96) per SD,P<0.05 | NA |
PEN | Tamaki et al.[ | 1285 (fracture: 25 vs. no fracture: 1260) | Male | Japanese | 73.1±5.1 | 5 | OF | 0.057 vs. 0.049 µg/ml | FN:HR=1.48, 95%CI(1.00-2.18); LS:HR=1.51, 95%CI(1.03-2.21) | NA |
esRAGE-to-PEN ratio | Tamaki et al.[ | 1285 (fracture: 25 vs. no fracture: 1260) | Male | Japanese | 73.1±5.1 | 5 | OF | (geometric mean ± SD) 3.6±1.8 vs. 4.9±0.9 | FN: HR=0.67, 95%CI(0.45-0.98); LS: HR=0.64, 95%CI(0.43-0.95) | NA |
CTX | Garnero et al.[ | 7598 (hip fracture: 109 vs. controls: 292) | Female | French | HF: 82.6±4.6; Controls: 82.5±4.5 | (mean) 22 months | HF | 305±163vs. 266± 150 µg/mmol Cr | NA | OR=2.2, 95%CI(1.3-3.6) |
CTX | Garneroet al.[ | 408 (fracture: 65 vs. controls: 343) | Female | French | Fracture: 67±9; Controls: 64±9 | (median) 6.8 | VF and peripheral fractures | 22.8±8.0vs. 21.2±8.5 µmmol/mmol Cr | NA | RR=4.5, 95%CI(2.0-10.1) |
beta-CTX | Yoshimura et al.[ | 400 (male: 199 vs. female: 200) | Male/female =1/1 | Japanese | Male: 59.4±11.4; Female: 59.8±11.6 | 10 | Spinal OF | Male: 0.187 ± 0.121 ng/ml; Female: 0.234 ± 0.145 ng/ml | NS | HR=1.80, P<0.001 |
NTX | Yoshimura et al.[ | 400 (male: 199 vs. female: 200) | Male/female =1/1 | Japanese | Male: 59.4±11.4; Female: 59.8±11.6 | 10 | Spinal OF | Male: 13.6±4.2 nmolBCE/L; Female:15.2±4.0 nmolBCE/L | NS | HR=1.96, P<0.01 |
PINP | Yoshimura et al.[ | 400 (male: 199 vs. female: 200) | Male/female =1/1 | Japanese | Male:59.4±11.4; Female: 59.8±11.6 | 10 | Spinal OF | Male: 38.2±19.5 ng/ml; Female: 50.1±21.9 ng/ml | HR=2.80, P<0.05 | HR=1.65, P<0.05 |
"
Molecules | References | Study design | Sample | Sample size | Gender | Ethnicity | Age (yrs) | Follow-up (yrs) | Phenotype | Concentration | Effect size or difference | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Male | Female | |||||||||||
Free deoxypyridinoline | Garnero et al.[ | Prospective | Urine | 7598 (HF: 109; Controls: 292) | Female | French | (mean±SD) HF: 82.6±4.6; Controls: 82.5±4.5 | (mean) 22 months | OF | 6.41±2.20vs. 5.80±1.94 nmol/mmol Cr | NA | OR=1.9, 95%CI(1.1-3.2) |
Deoxypyridinoline | Yoshimura et al.[ | Prospective | Urine | 400 (Male: 199; Female: 200) | Male/female =1/1 | Japanese | (mean±SD) Male:59.4±11.4; Female: 59.8±11.6 | 10 | Spinal OF | Male:3.06±1.53 pmol/lmol Cr; Female: 4.76±1.91 pmol/lmol Cr | NS | HR=1.40, P<0.05 |
Homocysteine | Gjesdalet al.[ | Prospective | Plasma | 4766 | Male/female=2127/2639 | Norway | 65-67 at enrollment | (mean) 12.6 | HF | 7-20 µmol/L | NS | HR=2.42, 95%CI (1.43-4.09) |
Homocysteine | Enneman et al.[ | Prospective | Plasma | 503 | Female | Netherlands | (median) 68.5 | (mean) 7 | OF | 9.4-11.6 μmol/L | NA | Adj. for age, BMI, FN-BMD, HR=1.82, 95%CI (1.02-3.22) |
DMG | Øyen et al.[ | Longitudinal | Plasma | 3310 | Male/female =1017/1204 | Norway | 71-74 | (mean) 10.8 | HF | 4.4±1.5 μmol/L | Adj. for BMD, HR=1.70, 95%CI (1.28-2.26) | |
S1P | Ardawi et al.[ | Prospective longitudinal | Plasma | 707 (Fracture: 138; No fracture: 569) | Female | Saudi Arabia | (mean) 61 | (median) 5.2±1.3 | OF | 7.23±0.79vs. 5.02±0.51 µmol/L | NA | Adj. HR=6.12, 95%CI(4.92-7.66) per SD increase. |
24, 25(OH)2D | Ginsberget al.[ | Longitudinal | Serum | 890 | Male/female =267/178 | 16% African-American | (mean) 78 | (mean) 8.4 | HF | 1.7±1.0 ng/ml | HR=0.73, 95%CI (0.61-0.87) per SD increase | |
VMR | Ginsberget al.[ | Longitudinal | Serum | 890 | Male/female =267/178 | 16% African-American | (mean) 78 | (mean) 8.4 | HF | 6.84±2.23 ng/ml | HR=0.74, 95%CI (0.61-0.88) per SD increase | |
25(OH)D | Swansonet al.[ | Prospective | Serum | 1000 (Q1: 144; Q2: 171; Q3: 113; Q4: 109) | Male | USA | 74.6±6.2 | (mean) 5.1 | Non-VF | Q1: 3.13-20.90; Q2: 20.91-25.90; Q3: 26-31; Q4: 31.10-55.80 ng/ml | Q1 (Q2,Q3,Q4 as ref.): HR=2.03, 95%CI (1.25-3.29) | NA |
1, 25(OH)2D | Swanson et al.[ | Prospective | Serum | 1000 (Q1: 144; Q2: 171; Q3: 113; Q4: 109) | Male | USA | 74.6±6.2 | (mean) 5.1 | Non-VF | Q1: 8.70-51.60; Q2: 51.70-62.00; Q3: 62.10-75.10; Q4: 75.20-142.00 ng/ml | Q1 (Q2,Q3,Q4 as ref.): HR=2.01, 95%CI (1.20-3.36) | NA |
PUFAs | Harris et al.[ | Longitudinal | Plasma | Fracture: 540; No fracture: 898 | OF: male/female=19/35; NF: male/female=429/469 | NA | OF:78.5±5.69; NF:76.5±5.48 | (median) 7 | OF | NA | HR=0.60, 95%CI(0.41-0.89) | Inverse association, Ptrend=0.06 |
"
Molecules | References | Study design | Sample | Sample size (n) | Gender | Ethnicity | Age (yrs) | Phenotype | Concentration | Effect size or difference |
---|---|---|---|---|---|---|---|---|---|---|
IGF-I | Sugimotoet al.[ | Cross-sectional | Serum | 165 | Female | Japanese | (mean) 62 | Spinal OF | NA | Lower in OF, P<0.01; cutoff 110 ng/ml provided a specificity of 81% with a sensitivity of 76% |
IGF-I | Nakaokaet al.[ | Cross-sectional | Serum | 205 | Female | Japanese | (mean) 64 | Spinal OF | NA | OR=0.19, 95%CI (0.07-0.59), P=0.003 |
IGFBP-3 | Sugimoto et al.[ | Cross-sectional | Serum | 165 | Female | Japanese | (mean) 62 | Spinal OF | NA | Lower in OF, P<0.01; cutoff 2.1 µg/ml provided a specificity of 81% with a sensitivity of 81% |
IGFBP-3 | Yamaguchi et al.[ | Cross-sectional | Serum | 193 (VF: 61; No fracture: 132) | Female | Japanese | (mean±SD) 62.5±8.0 | VF | 2.18±1.02vs. 3.23±1.07 μg/ml | OR=0.31, 95%CI (0.16-0.61), P=0.0007 |
Periostin | Kim et al.[ | Case-control | Plasma | 266 (VF: 133; Non-VF: 133) | Female | Korean | VFs: 62.7±6.4; Non-VFs: 63.0±6.3 | OF | Per SD increment | Any fracture: OR=1.50, 95%CI (1.14-1.97), P=0.003; non-VF: OR=1.59, 95%CI (1.12-2.24), P=0.009 |
Periostin | Yan et al.[ | Case-control | Serum | 367 (HF: 261; Controls: 106) | Female | Chinese | [median (IQR)]: HF: 80 (76-84); Controls: 78 (72-83) | HF | 45.51 (28.77-79.70) vs. 32.87 (19.71-53.58) ng/ml | FN-BMD: β=-0.390, P=0.004; LS-BMD:β=-0.158, P=0.190 |
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microRNAs | References | Study design | Sample size (n) | Sample | Expression trend in Casevs. Control | Fracture diagnostic value or difference | Phenotype |
---|---|---|---|---|---|---|---|
miR-21 | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.63, 95%CI (0.53-0.73), P = 0.013 | OF |
miR-23a | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.63, 95%CI (0.53-0.73), P=0.015 | OF |
miR-24 | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.63, 95%CI (0.53-0.74, P=0.013 | OF |
miR-93 | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.68, 95%CI (0.58-0.78), P=0.001 | OF |
miR-100 | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.69, 95%CI (0.60-0.78), P=0.0003 | OF |
miR122a | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.77, 95%CI (0.69-0.86), P<0.0001 | OF |
miR124a | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.69, 95%CI (0.59-0.78), P=0.0005 | OF |
miR125b | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.76, 95%CI (0.67-0.85), P<0.0001 | OF |
miR148a | Seeligeret al.[ | Case-control | Serum: 30+30*; Bone: 20+20* | Serum, bone tissue | Up-regulated | AUC: 0.61, 95%CI (0.51-0.72), P=0.038 | OF |
miR-21-5p | Panach et al.[ | Case-control | 15+12* | Serum | Up-regulated | Fold change=1.57, P=0.002 | OF |
miR-122-5p | Panach et al.[ | Case-control | 15+12* | Serum | Up-regulated | Fold change=5.48, P=0.00008 | OF |
miR-125b-5p | Panach et al.[ | Case-control | 15+12* | Serum | Up-regulated | Fold change=4.62, P=0.0003 | OF |
miR-328-3p | Weilneret al.[ | Cross-sectional | 37 | Serum | Down-regulated | Fold change=-1.54, -2.04, P<0.05 | OF |
let-7g-5p | Weilneret al.[ | Cross-sectional | 37 | Serum | Down-regulated | Fold change=-1.24, -1.89, P<0.05 | OF |
miR-19a-3p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.929, 95%CI (0.856-0.983) | Low traumatic fractures |
miR-19b-3p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.944, 95%CI (0.879-0.997) | Low traumatic fractures |
miR-30e-5p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.959, 95%CI (0.901-0.997) | Low traumatic fractures |
miR-140-5p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.947, 95%CI (0.900-0.983) | Low traumatic fractures |
miR-152-3p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.962, 95%CI (0.918-0.993) | Low traumatic fractures |
miR-324-3p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.950, 95%CI (0.885-0.994) | Low traumatic fractures |
miR-335-5p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.939, 95%CI (0.872-0.986) | Low traumatic fractures |
miR-550a-3p | Kocijan et al.[ | Case-control | 36+39* | Serum | Down-regulated | AUC: 0.909, 95%CI (0.837-0.970) | Low traumatic fractures |
hsa-miR-4516 | Mandourah et al.[ | Case-control | 139 | Serum, Plasma | Up-regulated | P=0.00014 | OF |
miR-140-3p | Ramírez-Salazaret al.[ | Case-control | 20+20* | Serum | Up-regulated | AUC: 0.92, P<0.0001 | OF |
miR-23b-3p | Ramírez-Salazaret al.[ | Case-control | 20+20* | Serum | Up-regulated | AUC: 0.88, P<0.0001 | OF |
"
Molecules | References | Study design | Sample | Sample size (n) | Gender | Ethnicity | Age§ (yrs) | Phenotype | Concentration | Effect size or difference in concentration or percentage | |
---|---|---|---|---|---|---|---|---|---|---|---|
Male | Female | ||||||||||
Urinary calcium | Rull et al.[ | Cross- sectional | Urine | OFs:55; Non-OFs:32 | Female | Spanish | OF: 70.1±13.8, Non-OF: 56.7±6.4 | OF | 8.95±0.73vs.9.19±0.38 mg/dl | NA | 40% vs. 18.8% hypercalciuria, P=0.04 |
Homocysteine | Kuroda et al.[ | Cross- sectional | Plasma | Grade 0: 1052; Grade 1: 137; Grade 2: 124; Grade 3: 162 | Female | Japanese | 66.6±9.0 | VF | Grade 0: 8.9±2.9, Grade 1: 9.2±2.8, Grade 2: 9.8±3.7, Grade 3: 11.3±5.3 µmol/L | NA | OR (95%CI): 1.22(1.03, 1.46)-1.27(1.04-1.58), P<0.05 |
Homocysteine | Zhu et al.[ | Cross- sectional | Plasma | OF: 39; HEF: 22; NF: 21 | Male/female =14/27 | Chinese | 80.61±5.61 (OF: 81.82±5.49, HEF: 78.88±5.75, Non-OF: 79.75±5.47) | OF | OF: 17.21±5.99, HEF: 10.82±3.60, Non-OF: 12.91±4.32 µmol/L | F=9.483, P= 0.000 | |
Homocysteine | Bahtiri et al.[ | Cross- sectional | Serum | Osteoporosis: 49; Normal: 33 | Female | NA | 56.53±5.84 | OF | 16.84±11.71vs. 13.09±2.53 µmol/L | NA | LS-BMD (r=-0.163, P<0.05), FN-BMD (r=-0.164, P<0.05) |
S1P | Kim et al.[ | Case-control | Plasma | VF: 69; Non-VF: 69 | Female | Korean | VF: 65.1±6.7; Non-VF: 64.9±6.5 | VF | 7.49±3.44vs. 5.58±2.01 µmol/L | NA | OR=9.33, 95%CI (2.68-32.49) |
S1P | Bae et al.[ | Longitudinal | Plasma | Treated with antiosteoporotic:172; Untreated: 76 | Female | Korean | Treated: 58.4±6.3; Untreated: 59.1±7.7, | OF | 4.90±0.2vs. 5.27±0.4 µmol/L | Highest tertile: 5.90-16.51 μmol/L | NA |
Retinol | Navarro-Valverdeet al.[ | Cross- sectional | Serum | 154 | Female | Spanish | >65 | OF | NA | NA | LS-BMD (r=-0.210, P<0.01), FN-BMD (r=-0.324, P<0.001) |
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