The assessment of fragility fracture risk based on bone densitometry and FRAX°, although commonly used, has shown some limitations. MicroRNAs (miRNAs) are promising biomarkers known to regulate post-transcriptional gene expression. Many studies have already shown that microRNAs are involved in bone homeostasis by modulating osteoblast and osteoclast gene expression. In this pilot study, we investigated the ability of an miRNA panel (namely, the OsteomiR° score) to predict fragility fracture risk in older people. miRNAs were extracted from the sera of 17 persons who developed a fracture within 3 years of collecting the serum and 16 persons who did not experience fractures in the same period. Nineteen miRNAs known to be involved in bone homeostasis were assessed, and 10 miRNAs were employed to calculate the OsteomiR° score. We found a trend towards higher OsteomiR° scores in individuals who experienced fractures compared to control subjects. The most suitable cut-off that maximized sensitivity and specificity was determined by ROC curve analysis, and a positive predictive value of 68% and a sensitivity of 76% were obtained. The OsteomiR° score was higher in osteopenic and osteoporotic subjects compared to subjects with a normal T score. Additionally, the OsteomiR° score predicted more fracture events than the recommended “need-to-treat” thresholds based on FRAX° 10-year probability. miRNAs reflect impairments in bone homeostasis several years before the occurrence of a fracture. The OsteomiR° score seems to be a promising miRNA panel for fragility fracture risk prediction and might have added value compared to FRAX°. Given the limited cohort size, further studies should be dedicated to validating the OsteomiR° score.
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Reginster JY, Burlet N (2006) Osteoporosis: a still increasing prevalence. Bone 38(2):4–9
Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22(3):465–475
Randell AG, Nguyen TV, Bhalerao N, Silverman SL, Sambrook PN, Eisman JA (2000) Deterioration in quality of life following hip fracture: a prospective study. Osteoporos Int 11(5):460–466
Melton LJ, Johnell O, Lau E, Mautalen CA, Seeman E (2004) Osteoporosis and the global competition for health care resources. J Bone Miner Res 19(7):1055–1058
Reid IR (2015) Efficacy, effectiveness and side effects of medications used to prevent fractures. J Intern Med 277(6):690–706
Camacho PM et al (2016) American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the diagnosis and treatment of postmenopausal osteoporosis-executive summary. Endocr Pract 22(4):1–42
Johnell O et al (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20(7):1185–1194
Siris ES et al (2001) Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. J Am Med Assoc 286(22):2815–2822
Kanis JA et al (2007) The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 18(8):1033–1046
Silverman SL, Calderon AD (2010) The utility and limitations of FRAX: a us perspective. Curr Osteoporos Rep 8(4):192–197
Sambrook PN et al (2007) Influence of fall related factors and bone strength on fracture risk in the frail elderly. Osteoporos Int 18(5):603–610
Giangregorio LM et al (2012) FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 27(2):301–308
Schwartz AV et al (2011) Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 305(21):2184–2192
Walter E, Dellago H, Grillari J, Dimai HP, Hackl M (2018) Cost-utility analysis of fracture risk assessment using microRNAs compared with standard tools and no monitoring in the Austrian female population. Bone 108:44–54
Hackl M, Heilmeier U, Weilner S, Grillari J (2016) Circulating microRNAs as novel biomarkers for bone diseases—complex signatures for multifactorial diseases? Mol Cell Endocrinol 432:83–95
Foessl I, Kotzbeck P, Obermayer-Pietsch B (2019) miRNAs as novel biomarkers for bone related diseases. J Lab Precis Med 4(2–2):2–2
Tie Y, Liu B, Fu H, Zheng X (2009) Circulating miRNA and cancer diagnosis. Sci China Ser C Life Sci 52(12):1117–1122
Meder B et al (2011) MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol 106(1):13–23
McClelland AD, Kantharidis P (2013) microRNA in the development of diabetic complications. Clin Sci 126(2):95–110
He P et al (2016) miR-141 modulates osteoblastic cell proliferation by regulating the target gene of IncRNA H19 and IncRNA H19-derived miR-675. Am J Transl Res 8(4):1780–1788
Li D et al (2016) Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun 7(1):10872
Zhao C et al (2015) miR-214 promotes osteoclastogenesis by targeting pten/pi3k/Akt pathway. RNA Biol 12(3):343–353
Cao F, Zhan J, Chen X, Zhang K, Lai R, Feng Z (2017) miR-214 promotes periodontal ligament stem cell osteoblastic differentiation by modulating Wnt/β-catenin signaling. Mol Med Rep 16(6):9301–9308
Tu B et al (2016) miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2. Cell Death Dis 7(10):e2436
Yin Q, Wang J, Fu Q, Gu S, Rui Y (2018) CircRUNX2 through has-miR-203 regulates RUNX2 to prevent osteoporosis. J Cell Mol Med 22(12):6112–6121
Peng H, Lu SL, Bai Y, Fang X, Huang H, Zhuang XQ (2018) MiR-133a inhibits fracture healing via targeting RUNX2/BMP2. Eur Rev Med Pharmacol Sci 22(9):2519–2526
Deng Y et al (2013) Effects of a miR-31, Runx2, and Satb2 regulatory loop on the osteogenic differentiation of bone mesenchymal stem cells. Stem Cells Dev 22(16):2278–2286
Zhang L et al (2017) Overexpression of MiR-335-5p promotes bone formation and regeneration in mice. J Bone Miner Res 32(12):2466–2475
Huang J, Song G, Yin Z, Fu Z, Ye Z (2017) MiR-29a and messenger RNA expression of bone turnover markers in canonical Wnt pathway in patients with ankylosing spondylitis. Clin Lab 63(5–6):955–960
Mäkitie RE, Hackl M, Niinimäki R, Kakko S, Grillari J, Mäkitie O (2018) Altered MicroRNA profile in osteoporosis caused by impaired WNT signaling. J. Clin. Endocrinol. Metab. 103(5):1985–1996
Cao Z et al (2014) MiR-422a as a potential cellular microRNA biomarker for postmenopausal osteoporosis. PLoS ONE 9(5):e97098
Seeliger C et al (2014) Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res 29(8):1718–1728
Kocijan R et al (2016) Circulating microRNA signatures in patients with idiopathic and postmenopausal osteoporosis and fragility fractures. J Clin Endocrinol Metab 101(11):4125–4134
Feichtinger X et al (2018) Bone-related circulating MicroRNAs miR-29b-3p, miR-550a-3p, and miR-324-3p and their Association to Bone Microstructure and Histomorphometry. Sci Rep 8(1):4867
Heilmeier U et al (2016) Serum miRNA signatures are indicative of skeletal fractures in postmenopausal women with and without type 2 diabetes and influence osteogenic and adipogenic differentiation of adipose tissue-derived mesenchymal stem cells in vitro. J Bone Miner Res 31(12):2173–2192
Beaudart C et al (2015) Quality of life and physical components linked to sarcopenia: the SarcoPhAge study. Exp Gerontol 69:103–110
Norlund L et al (1997) Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum β2-microglobulin/cystatin C-ratio. Scand J Clin Lab Investig 57(6):463–470
Johansson H et al (2011) A FRAX® model for the assessment of fracture probability in Belgium. Osteoporos Int 22(2):453–461
Briot K et al (2012) Actualisation 2012 des recommandations françaises du traitement médicamenteux de l’ostéoporose post-ménopausique. Revue du rhumatisme. 79(3):264–274
Chen Y, Alman BA (2009) Wnt pathway, an essential role in bone regeneration. J Cell Biochem 106(3):353–362
Kanis JA, Oden A, Johansson H, McCloskey E (2012) Pitfalls in the external validation of FRAX. Osteoporos Int 23(2):423–431
Aubry-Rozier B, Stoll D, Krieg MA, Lamy O, Hans D (2013) What was your fracture risk evaluated by FRAX® the day before your osteoporotic fracture? Clin Rheumatol 32(2):219–223
Chen XF, Li XL, Zhang H, Liu GJ (2014) Were you identified to be at high fracture risk by FRAX® before your osteoporotic fracture occurred? Clin Rheumatol 33(5):693–698
Watts NB, Ettinger B, LeBoff MS (2009) FRAX facts. J Bone Miner Res 24(6):975–979
Poynard T et al (2011) Applicability and precautions of use of liver injury biomarker FibroTest A reappraisal at 7 years of age. BMC Gastroenterol 11(39):39
We express our sincere thanks to Matthias Hackl, Susanna Skalicky and the TamiRNA GbmH team for providing technical support for the experiments.
This study was supported by clinical chemistry department and Fondation Léon Fredericq.
Conflict of interest
JYR is a member of paid advisory boards for IBSA-GENEVRIER, MYLAN, RADIUS HEALTH, PIERRE FABRE; upon invitation, is a paid lecturer of sponsor for IBSA-GENEVRIER, MYLAN, CNIEL, DAIRY RESEARCH COUNCIL (DRC) and received grant support from industry (all through the Institution) from IBSA-GENEVRIER, MYLAN, CNIEL, RADIUS HEALTH. All other authors state that they have no conflicts of interest.
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Ladang, A., Beaudart, C., Locquet, M. et al. Evaluation of a Panel of MicroRNAs that Predicts Fragility Fracture Risk: A Pilot Study. Calcif Tissue Int 106, 239–247 (2020). https://doi.org/10.1007/s00223-019-00628-8
- Fracture risk prediction