Armbrecht, G.

Duseja, A.

Eastell, R.

Evans, D.

Glüer, K.C.

Gossiel, F.

Hackl, M.

Paggiosi, M.

Reid, D.M.

Roux, C.

Vazquez, D.C.

Zarecki, P.

White Rose Research Online

Abstract citation ID: bvaf149.532Bone and Mineral MetabolismMON-790The Use Of Microrna Ratios To Predict Fractures InOlder Women: The Opus StudyDavid Carro Vazquez, PhD1, Patryk Zarecki2, Ankita Duseja3,MatthiasHackl4, KlausC.Glüer5, DavidM.Reid6, ChristianRoux7, Gabriele Armbrecht8, Fatma Gossiel2, Margaret Paggiosi2,Daniel Evans9, and Richard Eastell, MBChB, MD101UCSF, San Francisco, CA, USA; 2School of Medicine andPopulation Health, Division of Clinical Medicine, University ofSheffield, Sheffield, United Kingdom; 3Imperial College London,London, United Kingdom; 4TAmiRNA GmbH, Vienna, Austria;5Section Biomedical Imaging, Department of Radiology andNeuroradiology, University Medical Center Schleswig-Holstein(UKSH), Kiel University, Kiel, Germany; 6School of Medicine,Medical Sciences and Nutrition, University of Aberdeen,Aberdeen, United Kingdom; 7INSERM U1153, Paris DescartesUniversity, Rheumatology Department, Cochin Hospital, Paris,France; 8Department of Radiology, Charité-UniversitätsmedizinBerlin, Corporate Member of Freie Universität Berlin andHumboldt-Universität zu Berlin, Berlin, Germany; 9CaliforniaPacific Medical Center Research Institute, San Francisco, CA,USA; 10University of Sheffield, Sheffield, United KingdomDisclosure: D. Carro Vazquez: None. P. Zarecki:None. A. Duseja: None. M. Hackl: Matthias Hackl isCEO and founder of TAmiRNA GmbH. K.C. Glüer: None.D.M. Reid: None. C. Roux: None. G. Armbrecht: None.F. Gossiel: None. M. Paggiosi: None. D. Evans: None.R. Eastell: None.Introduction: Biomarkers may add to our ability topredict fracture risk in older women CirculatingmicroRNAs (miRNAs) have emerged as promising minim-ally invasive biomarkers for bone fragility. This study as-sessed whether serum miRNA ratios can predict incidentvertebral and nonvertebral fractures using a machinelearning (ML)-based approach independent of establishedrisk factors such as prior fracture and BMD. Methods:We analyzed 1,128 postmenopausal women aged 55 to 80from the population-based OPUS Study with baseline se-rum profiled using the osteomiR® miRNA kit, which quan-tifies 19 miRNAs by RT-qPCR. All pairwise miRNA ratioswere computed to evaluate predictive value for incidentfractures. During 6-year follow-up, 126 women sustainednonvertebral and 43 vertebral fractures. Logistic regres-sion models including clinical covariates were comparedto models that added miRNA ratios to the baseline model—individually in logistic regression and as selected combi-nations in ML-based Elastic Net. The baseline modelincluded age, BMI, total hip and lumbar spine BMD, preva-lent fracture status, and spike-in control (UniSp4).Model performance was evaluated using AUC and NetReclassification Improvement (NRI).Results: For nonverte-bral fractures, individual miRNA ratios added to logisticregression improved AUC from 0.599 to 0.662 (ANOVAp < 0.001) and NRI = 0.081 for hsa-miR-17-5p/hsa-miR-29b-3p, which had an odds ratio (OR) of 1.478 (p <0.001). The best ML model (AUC = 0.671, NRI = 0.114),using 20-fold cross-validation andElasticNet alpha= 1 (indi-cating pure L1 lasso regularization), selected four miRNAratios: hsa-miR-17-5p/hsa-miR-29b-3p, hsa-miR-143-3p/hsa-miR-29b-3p, hsa-miR-19b-3p/hsa-miR-29b-3p, andhsa-miR-188-5p/hsa-miR-550a-3p, with ORs ranging from1.041 to 1.315. For vertebral fractures, the individualratio hsa-miR-17-5p/hsa-miR-152-3p improved AUC from0.608 to 0.635, with NRI = 0.128 and OR = 1.406 (p <0.001). The bestMLmodel (AUC= 0.639,NRI= 0.096), usingJournal of the Endocrine Society | https://doi.org/10.1210/jendso/bvaf149 | A285J Endocrine Soc, Volume 9, Issue Supplement_1, October–November 2025A285Downloaded from https://academic.oup.com/jes/article/9/Supplement_1/bvaf149.532/8298977 by guest on 31 October 202510-fold cross-validation and alpha = 1, selected four miRNAratios: hsa-miR-144-5p/hsa-miR-152-3p, hsa-let-7b-5p/hsa-miR-451a, hsa-miR-133b/hsa-miR-152-3p, andhsa-miR-152-3p/hsa-miR-23a-3p, with ORs ranging from0.608 to 1.459. Adding bone turnover markers (BTMs), aloneor in combination with miRNA ratios, did not yield any im-provement in model performance using the same method-ology—whether added individually or as combinationsselected via ElasticNet.Discussion:CirculatingmiRNA ra-tios derived from qPCR can enhance fracture risk predictionbeyond clinical models.ML-based selection of informative ra-tios, followed by de novo logistic regression refitting with thebaseline model, improved both discrimination and reclassifi-cation. These findings support integrating circulatingmiRNA biomarkers into clinical tools for assessing fracturerisk in older women.Presentation: Monday, July 14, 20252 (T-score -4.2). Clinical risk factors for osteopor-osis include maternal history of osteoporosis. Laboratoryevaluation for secondary causes of osteoporosis was unre-vealing. She started teriparatide 20 mcg daily in August2020. Her bone density improved over the course of 2 years,but T-scores remained < -2.5. Due to her strong preferenceto continue teriparatide rather than transition to anothertreatment, she has continued teriparatide for 4 years and5 months to date. At 3 years 10 months of treatment, herlumbar spine bone density improved to 0.883 g/cm2(T-score -2.6) and procollagen I intact N-terminal propep-tide (P1NP) remains elevated at 214 ug/L. Trabecularbone score (TBS) did not improve . She has not sustainedany fractures since starting teriparatide. Side effectshave included minor injection site bleeding. This case dem-onstrates continued improvement in bone density with ex-tended teriparatide use beyond two years in apostmenopausal woman with osteoporosis complicated byA286 | Journal of the Endocrine Society | https://doi.org/10.1210/jendso/bvaf149J Endocrine Soc, Volume 9, Issue Supplement_1, October–November 2025 A286Downloaded from https://academic.oup.com/jes/article/9/Supplement_1/bvaf149.532/8298977 by guest on 31 October 2025

MON-790 The use of microrna ratios to predict fractures in older women: the opus study

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MON-790 The use of microrna ratios to predict fractures in older women: the opus study

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