{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:42:51Z","timestamp":1760236971726,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH NIMHHD 2G12MD007592"],"award-info":[{"award-number":["NIH NIMHHD 2G12MD007592"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Accurate clinical evaluation of renal osteodystrophy (ROD) is currently accomplished using invasive in vivo transiliac bone biopsy, followed by in vitro histomorphometry. In this study, we demonstrate that an alternative method for ROD assessment is through a fast, label-free Raman recording of multiple biomarkers combined with computational analysis for predicting the minimally required number of spectra for sample classification at defined accuracies. Four clinically relevant biomarkers: the mineral-to-matrix ratio, the carbonate-to-matrix ratio, phenylalanine, and calcium contents were experimentally determined and simultaneously considered as input to a linear discriminant analysis (LDA). Additionally, sample evaluation was performed with a linear support vector machine (LSVM) algorithm, with a 300 variable input. The computed probabilities based on a single spectrum were only marginally different (~80% from LDA and ~87% from LSVM), both providing an unacceptable classification power for a correct sample assignment. However, the Type I and Type II assignment errors confirm that a relatively small number of independent spectra (7 spectra for Type I and 5 spectra for Type II) is necessary for a p &lt; 0.05 error probability. This low number of spectra supports the practicality of future in vivo Raman translation for a fast and accurate ROD detection in clinical settings.<\/jats:p>","DOI":"10.3390\/diagnostics10020079","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T11:55:56Z","timestamp":1580471756000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assessment of Renal Osteodystrophy via Computational Analysis of Label-free Raman Detection of Multiple Biomarkers"],"prefix":"10.3390","volume":"10","author":[{"given":"Marian","family":"Manciu","sequence":"first","affiliation":[{"name":"Department of Physics, University of Texas at El Paso, El Paso, TX 79968, USA"},{"name":"Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin E.","family":"Bennet","sequence":"additional","affiliation":[{"name":"Division of Engineering and Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avudaiappan","family":"Maran","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Biomaterials and Histomorphometry Core Laboratory, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Yaszemski","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery and Biomaterials and Histomorphometry Core Laboratory, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa A.","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Magiricu","sequence":"additional","affiliation":[{"name":"Touro College of Osteopathic Medicine, New York, NY 10027, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicia S.","family":"Manciu","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Texas at El Paso, El Paso, TX 79968, USA"},{"name":"Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"ref_1","unstructured":"Seibel, M., Robins, S., and Bilezikian, J. (2006). The Central Control of Bone Remodeling. Dynamics of Bone and Cartilage Metabolism, Elsevier, Academic Press. [2nd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4103\/2230-8210.192914","article-title":"Bone turnover markers: Emerging tool in the management of osteoporosis","volume":"20","author":"Shetty","year":"2016","journal-title":"Indian J. Endocr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00198-009-0838-9","article-title":"Bone turnover markers: Understanding their value in clinical trials and clinical practice","volume":"20","author":"Civitelli","year":"2009","journal-title":"Osteoporos Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1038\/sj.ki.5000414","article-title":"Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"69","author":"Moe","year":"2006","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Malluche, H.H., and Faugere, M.-C. (1986). Atlas of Mineralized Bone Histology, Karger.","DOI":"10.1159\/isbn.978-3-318-04339-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1681\/ASN.2010121253","article-title":"Differences in Bone Quality in Low- and High-Turnover Renal Osteodystrophy","volume":"23","author":"Malluche","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/ki.2013.254","article-title":"Recent advances in the noninvasive diagnosis of renal osteodystrophy","volume":"84","author":"Moorthi","year":"2013","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1002\/jbmr.309","article-title":"Renal osteodystrophy in the first decade of the new millennium: Analysis of 630 bone biopsies in black and white patients","volume":"26","author":"Malluche","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S140","DOI":"10.2215\/CJN.02430508","article-title":"The role of bone biopsy in patients with chronic renal failure","volume":"3","author":"Miller","year":"2008","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1507\/endocrj1954.26.Supplement_81","article-title":"Age-related changes of renal osteodystrophy","volume":"26","author":"Morii","year":"1979","journal-title":"Endocrinol Jpn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/8756-3282(93)90209-S","article-title":"Cortical aging differences and fracture implications for the human femoral neck","volume":"14","author":"Boyce","year":"1993","journal-title":"Bone"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1177\/0022034510377791","article-title":"Aging and bone","volume":"89","author":"Boskey","year":"2010","journal-title":"J. Dent. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.jocd.2010.06.002","article-title":"In vivo precision of the GE Lunar iDXA densitometer for the measurement of total-body, lumbar spine, and femoral bone mineral density in adults","volume":"13","author":"Hind","year":"2010","journal-title":"J. Clin. Densitom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1681\/ASN.2009121208","article-title":"Bone Mass and Microarchitecture in CKD Patients with Fracture","volume":"21","author":"Nickolas","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1007\/s11999-010-1692-y","article-title":"Raman Assesment of Bone Quality","volume":"469","author":"Morris","year":"2011","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jbmr.2356","article-title":"Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model","volume":"30","author":"McNerny","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.2337\/dc13-0510","article-title":"Alterations to bone mineral composition as an early indication of osteomyelitis in the diabetic foot","volume":"36","author":"Holmes","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00774-014-0599-1","article-title":"Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: A murine mandibular model","volume":"33","author":"Felice","year":"2015","journal-title":"J. Bone Miner. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1016\/j.bone.2006.06.008","article-title":"Bone tissue compositional differences in women with and without osteoporotic fracture","volume":"39","author":"McCreadie","year":"2006","journal-title":"Bone"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jbiomech.2012.11.039","article-title":"Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis","volume":"46","author":"Inzana","year":"2013","journal-title":"J. Biomech."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1002\/jor.23248","article-title":"Osteolytic and mixed cancer metastasis modulates collagen and mineral parameters within rat vertebral bone matrix","volume":"34","author":"Burke","year":"2016","journal-title":"J. Orthop. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jbiomech.2010.10.009","article-title":"Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse model","volume":"44","author":"Bi","year":"2011","journal-title":"J. Biomech."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/jbmr.2768","article-title":"Novel Raman Spectroscopic Biomarkers Indicate That Postyield Damage Denatures Bone\u2019s Collagen","volume":"31","author":"Unal","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111606-1","DOI":"10.1117\/1.JBO.19.11.111606","article-title":"Development of Raman spectral markers to assess metastatic bone in breast cancer","volume":"19","author":"Ding","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ciubuc, J.D., Manciu, M., Maran, A., Yaszemski, M.J., Sundin, E.M., Bennet, K.E., and Manciu, F.S. (2018). Raman Spectroscopic and Microscopic Analysis for Monitoring Renal Osteodystrophy Signatures. Biosensors, 8.","DOI":"10.3390\/bios8020038"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1359\/jbmr.090414","article-title":"Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture","volume":"24","author":"Faibish","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"031102","DOI":"10.1117\/1.1922927","article-title":"Infrared analysis of bone in health and disease","volume":"10","author":"Boskey","year":"2005","journal-title":"J. Biomed. Opt."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1016\/j.biomaterials.2006.11.043","article-title":"FT-IR Imaging of Native and Tissue-Engineered Bone and Cartilage","volume":"28","author":"Boskey","year":"2007","journal-title":"Biomaterials"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s002239900372","article-title":"FTIR Microspectroscopic Analysis of Human Iliac Crest Biopsies from Untreated Osteoporotic Bone","volume":"61","author":"Paschalis","year":"1997","journal-title":"Calcif. Tissue Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1002\/jbmr.10","article-title":"Infrared spectroscopy indicates altered bone turnover and remodeling activity in renal osteodystrophy","volume":"25","author":"Isaksson","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"065002","DOI":"10.1117\/1.JBO.19.6.065002","article-title":"Relationship between the V2PO4\/amide III ratio assessed by Raman spectroscopy and the calcium content measured by quantitative backscattered electron microscopy in healthy human osteonal bone","volume":"19","author":"Roschger","year":"2014","journal-title":"J. Biomed. Opt."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wasserman, L. (2003). Springer Texts in Statistics. All of Statistics. A Concise Course in Statistical Inference, Springer Science + Business Media, LLC.","DOI":"10.1007\/978-0-387-21736-9"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1046\/j.1525-1594.1998.06198.x","article-title":"Renal Osteodystrophy in Dialysis Patients: Diagnosis and Treatment","volume":"22","author":"Fournier","year":"1998","journal-title":"Artif. Organs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2337\/diaspect.21.1.19","article-title":"Secondary Hyperparathyroidism and Chronic Kidney Disease","volume":"21","author":"Tomasello","year":"2008","journal-title":"Diabetes Spectr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s11914-017-0368-x","article-title":"Calcium Balance in Chronic Kidney Disease","volume":"15","author":"Spiegel","year":"2017","journal-title":"Curr. Osteoporos. Rep."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/2\/79\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:31Z","timestamp":1760172811000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/2\/79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,31]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["diagnostics10020079"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10020079","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2020,1,31]]}}}