{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:51:18Z","timestamp":1785797478073,"version":"3.56.0"},"reference-count":110,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Malaysia Ministry of Higher Education (MoHE) through the Fundamental Research Grants Scheme (FRGS)","award":["FRGS\/1\/2020\/SKK0\/UKM\/02\/27"],"award-info":[{"award-number":["FRGS\/1\/2020\/SKK0\/UKM\/02\/27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Gingival crevicular fluid (GCF) and oral fluid have emerged as promising diagnostic tools for detecting biomarkers. This review aimed to evaluate the existing literature on using oral fluids as a source of biomarkers for bone turnover diseases affecting the jawbone. A comprehensive search strategy was executed between August 2014 and August 2024 across five major databases (Web of Science, EBSCOhost Dentistry &amp; Oral Sciences Source, Cochrane Library, Scopus, and PubMed) and grey literature sources. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was applied. The screening was facilitated using Rayyan at rayyan.ai and Endnote X20 software tools, culminating in the evaluation of 14,965 citations from databases and 34 from grey literature. Following rigorous scrutiny, 37 articles were selected for inclusion in this review, encompassing diseases such as periodontitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoporosis. The quality of the included observational studies was assessed using the Revised Risk of Bias Assessment Tool for Non-Randomized Studies (RoBANS 2). Interleukin-1 beta (IL-1\u03b2), sclerostin, osteoprotegerin (OPG), and interleukin-34 (IL-34) emerged as significant biomarkers in GCF, and they were mainly from periodontitis and osteoporosis. Osteocalcin (OC), IL-1\u03b2, tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), OPG, and matrix metalloproteinase-9 (MMP-9) were significant in oral fluid or saliva, and they were from periodontitis, MRONJ, and osteoporosis. These findings underscore the potential use of oral fluids, which are regarded as non-invasive tools for biomarker identification in bone turnover. Many biomarkers overlap, and it is important to identify other specific biomarkers to enable accurate diagnosis of these conditions.<\/jats:p>","DOI":"10.3390\/diagnostics14192184","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T04:00:04Z","timestamp":1727668804000},"page":"2184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Oral and Gingival Crevicular Fluid Biomarkers for Jawbone Turnover Diseases: A Scoping Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4012-9033","authenticated-orcid":false,"given":"Nurfatima Azzahra","family":"Fadli","sequence":"first","affiliation":[{"name":"Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6856-8511","authenticated-orcid":false,"given":"Mariati","family":"Abdul Rahman","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Diagnostics and Biosciences, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-9554","authenticated-orcid":false,"given":"Saiful Anuar","family":"Karsani","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7445-0205","authenticated-orcid":false,"given":"Roszalina","family":"Ramli","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/ejo\/cjab077","article-title":"Bone turnover markers in gingival crevicular fluid and blood serum of patients with fixed orthodontic appliances","volume":"44","author":"Kloukos","year":"2022","journal-title":"Eur. J. Orthod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.51847\/Z8ruHjG41y","article-title":"Assessment of bone turnover markers prior to dental implant placement for osteoporosis patient-A case-control study","volume":"11","author":"Nirubama","year":"2023","journal-title":"Ann. Dent. Spec."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1373\/clinchem.2016.259085","article-title":"Bone turnover markers in the diagnosis and monitoring of metabolic bone disease","volume":"63","author":"Greenblatt","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.joms.2013.11.005","article-title":"Is bone turnover of jawbone and its possible over suppression by bisphosphonates of etiologic importance in pathogenesis of bisphosphonate-related osteonecrosis?","volume":"72","author":"Ristow","year":"2014","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.4317\/medoral.18298","article-title":"Osteoporosis, jawbones and periodontal disease","volume":"18","author":"Guiglia","year":"2013","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_6","first-page":"e26","article-title":"Biomarkers to predict the onset of biphosphonate-related osteonecrosis of the jaw: A systematic review","volume":"24","year":"2019","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/prd.12422","article-title":"Osteoporosis and periodontal diseases\u2013An update on their association and mechanistic links","volume":"89","author":"Yu","year":"2022","journal-title":"Periodontology 2000"},{"key":"ref_8","first-page":"e6699","article-title":"Bone Turnover markers in chronic periodontitis: A literature review","volume":"12","author":"Shazam","year":"2020","journal-title":"Cureus"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ahmad, A., Imran, M., and Ahsan, H. (2023). Biomarkers as biomedical bioindicators: Approaches and techniques for the detection, analysis, and validation of novel biomarkers of diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061630"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13323","DOI":"10.1016\/j.heliyon.2023.e13323","article-title":"Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of COVID-19 and other diseases","volume":"9","author":"Bodaghi","year":"2023","journal-title":"Heliyon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1039\/C5AN00780A","article-title":"Biomarker detection for disease diagnosis using cost-effective microfluidic platforms","volume":"140","author":"Sanjay","year":"2015","journal-title":"Analyst"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1128\/CDLI.5.4.507-512.1998","article-title":"Oral fluids as an alternative to serum for measurement of markers of immune activation","volume":"5","author":"Nishanian","year":"1998","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bibi, T., Khurshid, Z., Rehman, A., Imran, E., Srivastava, K.C., and Shrivastava, D. (2021). Gingival crevicular fluid (GCF): A diagnostic tool for the detection of periodontal health and diseases. Molecules, 26.","DOI":"10.3390\/molecules26051208"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Abouzaid, M., Howidi, N., Badran, Z., Mohammed, G., and Mousa, N.A. (2023). The potential role of the gingival crevicular fluid biomarkers in the prediction of pregnancy complications. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1168625"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kim, H.D., Karna, S., Shin, Y., Vu, H., Cho, H.J., and Kim, S. (2021). S100A8 and S100A9 in saliva, blood and gingival crevicular fluid for screening established periodontitis: A cross-sectional study. BMC Oral Health, 21.","DOI":"10.1186\/s12903-021-01749-z"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e23782","DOI":"10.1016\/j.heliyon.2023.e23782","article-title":"Salivary and gingival crevicular fluid biomarkers of periodontal health and\/or obesity among children and adolescents: A systematic review and meta-analysis","volume":"10","author":"Deng","year":"2023","journal-title":"Heliyon"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1007\/s00784-023-05169-x","article-title":"Biomarkers for diagnosis of Stage III, Grade C with molar incisor pattern periodontitis in children and young adults: A systematic review and meta-analysis","volume":"27","author":"Alamri","year":"2023","journal-title":"Clin. Oral Investig."},{"key":"ref_18","unstructured":"Farid, B. (2021). Orthodontic therapeutic biomarkers in saliva and gingival crevicular fluid. Current Trends in Orthodontics, Intech Open."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/prd.12107","article-title":"Gingival crevicular fluid as a source of biomarkers for periodontitis","volume":"70","author":"Barros","year":"2016","journal-title":"Periodontoly 2000"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Aguiar, M., Perinetti, G., and Capelli, J.J. (2017). The gingival crevicular fluid as a source of biomarkers to enhance efficiency of orthodontic and functional treatment of growing patients. Biomed. Res. Int., 2017.","DOI":"10.1155\/2017\/3257235"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"155504","DOI":"10.1016\/j.cyto.2021.155504","article-title":"Profiling of cytokines, chemokines and growth factors in saliva and gingival crevicular fluid","volume":"142","author":"Yong","year":"2021","journal-title":"Cytokine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S135","DOI":"10.4103\/JPBS.JPBS_56_19","article-title":"Gingival crevicular fluid: An overview","volume":"11","author":"Subbarao","year":"2019","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/cid.12694","article-title":"Use of IL-1 \u03b2, IL-6, TNF-\u03b1, and MMP-8 biomarkers to distinguish peri-implant diseases: A systematic review and meta-analysis","volume":"21","author":"Ghassib","year":"2019","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40510-017-0195-8","article-title":"A review of biomarkers in peri-miniscrew implant crevicular fluid (PMICF)","volume":"18","author":"Kaur","year":"2017","journal-title":"Prog. Orthod."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, M., Baeza, M., Contreras, J., Sorsa, T., Tervahartiala, T., Vald\u00e9s, M., Chaparro, A., and Hern\u00e1ndez-R\u00edos, P. (2020). MMP-8, TRAP-5, and OPG levels in GCF diagnostic potential to discriminate between healthy patients\u2019, mild and severe periodontitis sites. Biomolecules, 10.","DOI":"10.3390\/biom10111500"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117503","DOI":"10.1016\/j.cca.2023.117503","article-title":"Saliva biomarkers in oral disease","volume":"548","author":"Zhou","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41368-022-00209-w","article-title":"Promising applications of human-derived saliva biomarker testing in clinical diagnostics","volume":"15","author":"Song","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115781","DOI":"10.1016\/j.trac.2019.115781","article-title":"Saliva sampling: Methods and devices. An overview","volume":"124","author":"Bellagambi","year":"2020","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100503","DOI":"10.1007\/s12032-016-0863-4","article-title":"Salivary biomarkers in cancer detection","volume":"34","author":"Wang","year":"2017","journal-title":"Med. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"823","DOI":"10.7150\/ijms.25146","article-title":"Compliance with saliva collection protocol in healthy volunteers: Strategies for managing risk and errors","volume":"15","author":"Bhattarai","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3664516","DOI":"10.1155\/2022\/3664516","article-title":"Salivary biomarkers in periodontitis patients: A pilot study","volume":"2022","author":"Reddahi","year":"2022","journal-title":"Int. J. Dent."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chiamulera, M.M.A., Zancan, C.B., Remor, A.P., Cordeiro, M.F., Gleber-Netto, F.O., and Baptistella, A.R. (2021). Salivary cytokines as biomarkers of oral cancer: A systematic review and meta-analysis. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-07932-3"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Singh, P., Verma, J.K., and Singh, J.K. (2020). Validation of Salivary markers, il-1\u03b2, il-8 and lgals3bp for detection of oral squamous cell carcinoma in an indian population. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-64494-3"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.archoralbio.2017.12.022","article-title":"Diagnostic potential and future directions of biomarkers in gingival crevicular fluid and saliva of periodontal diseases: Review of the current evidence","volume":"87","author":"Ghallab","year":"2018","journal-title":"Arch. Oral Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4082\/kjfm.23.0034","article-title":"RoBANS 2: A Revised Risk of Bias Assessment Tool for Nonrandomized Studies of Interventions","volume":"44","author":"Seo","year":"2023","journal-title":"Korean J. Fam. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"155","DOI":"10.14715\/cmb\/2024.70.6.24","article-title":"Evaluation of temporomandibular joint morphology and morphometry in male osteoporotic patients using advanced imaging and biochemical markers: A cross-sectional study","volume":"70","author":"Kareem","year":"2024","journal-title":"Cell. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4103\/ijdr.ijdr_112_23","article-title":"Salivary interleukin-6 as a non-invasive biomarker for chronic periodontitis and tooth loss in Type 2 Diabetes","volume":"35","author":"Sangappa","year":"2024","journal-title":"Indian J. Dent. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.34172\/japid.2023.009","article-title":"Assessment of sclerostin levels in the gingival crevicular fluid of patients with periodontitis: A clinico-biochemical cross-sectional study","volume":"15","author":"Ashifa","year":"2023","journal-title":"J. Adv. Periodontol. Implant Dent."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1002\/JPER.22-0750","article-title":"Gingival crevicular fluid periodontal ligament-associated protein-1, sclerostin, and tumor necrosis factor-alpha levels in periodontitis","volume":"94","author":"Afacan","year":"2023","journal-title":"J. Periodontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1111\/odi.14201","article-title":"Quantitative proteomics in medication-related osteonecrosis of the jaw: A proof-of-concept study","volume":"29","author":"Bravo","year":"2023","journal-title":"Oral Dis."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Relvas, M., Silvestre, R., Gon\u00e7alves, M., Cabral, C., Mendes-Frias, A., Monteiro, L., and Viana da Costa, A. (2023). Analysis of salivary levels of IL-1\u03b2, IL17A, OPG and RANK-L in Periodontitis using the 2017 classification of periodontal diseases-an exploratory observational study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12031003"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4103\/jisp.jisp_390_21","article-title":"Protein and mRNA expression of interleukin-33 in periodontally diseased and healthy individuals and impact of nonsurgical periodontal therapy in salivary IL-33 levels","volume":"27","author":"Renjith","year":"2023","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_44","first-page":"1825","article-title":"Expression of selected inflammatory proteins and metalloproteinases in periodontitis","volume":"26","author":"Urban","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Nair, V., Grover, V., Arora, S., Das, G., Ahmad, I., Ohri, A., Sainudeen, S., Saluja, S., and Saha, A. (2022). comparative evaluation of gingival crevicular fluid Interleukin-17, 18 and 21 in different stages of periodontal health and disease. Medicina, 58.","DOI":"10.3390\/medicina58081042"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/JPER.22-0005","article-title":"Common complement factor H polymorphisms are linked with periodontitis in elderly patients","volume":"93","author":"Salminen","year":"2022","journal-title":"J. Periodontol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4274\/meandros.galenos.2021.50251","article-title":"Measurement of Oncostatin M, Leukemia Inhibitory Factor, and Interleukin-11 Levels in Serum, Saliva, and Gingival Crevicular Fluid of Patients with Periodontal Diseases","volume":"22","author":"Aydin","year":"2021","journal-title":"Meand. Med. Dent. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S1275","DOI":"10.4103\/jpbs.jpbs_90_21","article-title":"Evaluation of gingival crevicular fluid and serum tartrate-resistant acid phosphatase levels in subjects with clinically healthy periodontium and chronic periodontitis\u2013A clinico-biochemical study","volume":"13","author":"Baddam","year":"2021","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Badros, A.Z., Meddeb, M., Weikel, D., Philip, S., Milliron, T., Lapidus, R., Hester, L., Goloubeva, O., Meiller, T.F., and Mongodin, E.F. (2021). Prospective observational study of bisphosphonate-related osteonecrosis of the jaw in multiple myeloma: Microbiota profiling and cytokine expression. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.704722"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4274\/meandros.galenos.2021.09821","article-title":"Effect of non surgical periodontal treatment on gingival crevicular fluid Interleukin-1beta and Interleukin-37 in different periodontal diseases","volume":"22","author":"Toker","year":"2021","journal-title":"Meand. Med. Dent. J."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Joseph, B., Javali, M.A., Khader, M.A., AlQahtani, S.M., and Amanullah, M. (2020). Salivary osteocalcin as potential diagnostic marker of periodontal bone destruction among smokers. Biomolecules, 10.","DOI":"10.3390\/biom10030380"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4103\/jisp.jisp_256_19","article-title":"Evaluation of deoxypyridinoline levels in gingival crevicular fluid and serum as alveolar bone loss biomarker in patients with periodontitis","volume":"24","author":"Syed","year":"2020","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2147\/CCIDE.S199680","article-title":"The effect of Phase 1 periodontal treatment on the salivary RANKL\/OPG ratio in severe chronic periodontitis","volume":"11","author":"Moghadam","year":"2019","journal-title":"Clin. Cosmet. Investig. Dent."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.sdentj.2019.03.010","article-title":"Comparative evaluation of gingival crevicular fluid (GCF) levels of Interleukin-34 levels in periodontally healthy and in patients with chronic and aggressive periodontitis-A cross-sectional study","volume":"31","author":"Batra","year":"2019","journal-title":"Saudi Dent. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jds.2019.03.002","article-title":"Diagnostic accuracy of salivary biomarkers of bone turnover in identifying patients with periodontitis in a Saudi Arabian population","volume":"14","author":"Betsy","year":"2019","journal-title":"J. Dent. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"440","DOI":"10.5114\/ceji.2019.92806","article-title":"Pathogen profile and MMP-3 levels in areas with varied attachment loss in generalized aggressive and chronic periodontitis","volume":"44","author":"Yilmaz","year":"2019","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_57","first-page":"10","article-title":"Estimation of salivary tumour necrosis factor-\u03b1 levels in post-menopausal women with chronic periodontitis","volume":"12","author":"Agrawal","year":"2018","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"280","DOI":"10.4103\/ijdr.IJDR_527_17","article-title":"Effect of nonsurgical periodontal therapy on interleukin-34 levels in periodontal health and disease","volume":"29","author":"Guruprasad","year":"2018","journal-title":"Indian J. Dent. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/jcpe.12670","article-title":"Mucin 4 and matrix metalloproteinase 7 as novel salivary biomarkers for periodontitis","volume":"44","author":"Lundmark","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2334\/josnusd.16-0241","article-title":"Effect of bisphosphonate as an adjunct treatment for chronic periodontitis on gingival crevicuar fluid levels of nuclear factor-\u03baB ligand (RANKL) and osteoprotegerin in postmenopausal osteoporosis","volume":"59","author":"Sakallioglu","year":"2017","journal-title":"J. Oral Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/ehf2.12126","article-title":"Periodontitis and bone metabolism in patients with advanced heart failure and after heart transplantation","volume":"4","author":"Mizani","year":"2017","journal-title":"ESC Heart Fail."},{"key":"ref_62","first-page":"ZC122","article-title":"Comparative analysis of salivary alkaline phosphatase in post menopausal women with and without periodontitis","volume":"11","author":"Sophia","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_63","first-page":"386","article-title":"The assessment of IL-6 and RANKL in the association between chronic periodontitis and osteoporosis","volume":"67","author":"Ursarescu","year":"2016","journal-title":"Rev. Chim."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"152","DOI":"10.4103\/0970-9290.159145","article-title":"Estimation of N-terminal telopeptides of type I collagen in periodontal health, disease and after nonsurgical periodontal therapy in gingival crevicular fluid: A clinico-biochemical study","volume":"26","author":"Aruna","year":"2015","journal-title":"Indian J. Dent. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S470","DOI":"10.4103\/0975-7406.163507","article-title":"Comparative analysis of gingival crevicular fluid a disintegrin and metalloproteinase 8 levels in health and periodontal disease: A clinic-biochemical study","volume":"7","author":"Elavarasu","year":"2015","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"341259","DOI":"10.1155\/2015\/341259","article-title":"Effect of periodontal surgery on osteoprotegerin levels in gingival crevicular fluid, saliva, and gingival tissues of chronic periodontitis patients","volume":"2015","author":"Hassan","year":"2015","journal-title":"Dis. Markers"},{"key":"ref_67","first-page":"ZC50","article-title":"Evaluation of salivary levels of pyridinoline cross linked carboxyterminal telopeptide of type i collagen (ICTP) in periodontal health and disease","volume":"9","author":"Mishra","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1902\/jop.2015.140546","article-title":"Periodontal health in women with early-stage postmenopausal breast cancer newly on aromatase inhibitors: A pilot study","volume":"86","author":"Taichman","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/odi.12204","article-title":"Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw","volume":"21","author":"Michalowicz","year":"2015","journal-title":"Oral Dis."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fine, D.H., Markowitz, K., Fairlie, K., Tischio-Bereski, D., Ferrandiz, J., Godboley, D., Furgang, D., Gunsolley, J., and Best, A. (2014). Macrophage inflammatory protein-1\u03b1 shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098541"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Khongkhunthian, S., Kongtawelert, P., Ongchai, S., Pothacharoen, P., Sastraruji, T., Jotikasthira, D., and Krisanaprakornkit, S. (2014). Comparisons between two biochemical markers in evaluating periodontal disease severity: A cross-sectional study. BMC Oral Health, 14.","DOI":"10.1186\/1472-6831-14-107"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3892\/etm.2014.2071","article-title":"Tartrate-resistant acid phosphatase 5b is a marker of osteoclast number and volume in RAW 264.7 cells treated with receptor-activated nuclear \u03baB ligand","volume":"9","author":"Lv","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.sdentj.2022.01.003","article-title":"Medication-related osteonecrosis of the jaw (MRONJ): A review of pathophysiology, risk factors, preventive measures and treatment strategies","volume":"34","author":"AlRowis","year":"2022","journal-title":"Saudi Dent. J."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Lorenzo-Pouso, A.I., Bag\u00e1n, J., Bag\u00e1n, L., G\u00e1ndara-Vila, P., Chamorro-Petronacci, C.M., Castelo-Baz, P., Blanco-Carri\u00f3n, A., Blanco-Fern\u00e1ndez, M.A., Alvarez-Calder\u00f3n, O., and Carballo, J. (2021). Medication-related osteonecrosis of the jaw: A critical narrative review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194367"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.bjorl.2020.09.010","article-title":"Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients","volume":"88","author":"Kemp","year":"2022","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e0432","DOI":"10.1097\/MD.0000000000010432","article-title":"Associations between bone-alkaline phosphatase and bone mineral density in adults with and without diabetes","volume":"97","author":"Chen","year":"2018","journal-title":"Medicine"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bellei, E., Bertoldi, C., Monari, E., and Bergamini, S. (2022). Proteomics disclose the potential of gingival crevicular fluid (gcf) as a source of biomarkers for severe periodontitis. Materials, 15.","DOI":"10.3390\/ma15062161"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Khurshid, Z., Mali, M., Naseem, M., Najeeb, S., and Zafar, M.S. (2017). Human gingival crevicular fluids (GCF) proteomics: An overview. Dent. J., 5.","DOI":"10.3390\/dj5010012"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/jcpe.13630","article-title":"Discovery, validation, and diagnostic ability of multiple protein-based biomarkers in saliva and gingival crevicular fluid to distinguish between health and periodontal diseases","volume":"49","author":"Grant","year":"2022","journal-title":"J. Clin. Periodontol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41368-023-00231-6","article-title":"Salivary biomarkers: Novel noninvasive tools to diagnose chronic inflammation","volume":"15","author":"Dongiovanni","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Brescia, V., Cazzolla, A.P., Fontana, A., Varraso, L., Capobianco, C., Lovero, R., Lo Muzio, L., Dioguardi, M., Faienza, M.F., and Crincoli, V. (2023). Bone biomarkers measured on salivary matrix: Study of biological variability in a cohort of young subjects. Appl. Sci., 13.","DOI":"10.3390\/app131810234"},{"key":"ref_82","first-page":"9967311","article-title":"Monitoring salivary levels of interleukin 1 beta (il-1\u03b2) and vascular endothelial growth factor (VEGF) for two years of orthodontic treatment: A prospective pilot study","volume":"2021","author":"Naoumova","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Romano, F., Iaderosa, G., Corana, M., Perotto, S., Baima, G., Di Scipio, F., Abbadessa, G., Mariani, G.M., Aimetti, M., and Berta, G.N. (2022). Comparing ionic profile of gingival crevicular fluid and saliva as distinctive signature of severe periodontitis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030687"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gregorczyk-Maga, I., Szustkiewicz-Karo\u0144, A., Gajda, M., Kapusta, M., Maga, W., and Sch\u00f6nborn, M. (2023). The concentration of pro-and antiangiogenic factors in saliva and gingival crevicular fluid compared to plasma in patients with peripheral artery disease and type 2 diabetes. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061596"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s44174-023-00090-z","article-title":"A review on saliva-based health diagnostics: Biomarker selection and future directions","volume":"2","author":"Kumari","year":"2023","journal-title":"Biomed. Mater. Devices"},{"key":"ref_86","first-page":"1804727","article-title":"identification of gingival crevicular fluid sampling, analytical methods, and oral biomarkers for the diagnosis and monitoring of periodontal diseases: A systematic review","volume":"2016","author":"Philip","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Preian\u00f2, M., Savino, R., Villella, C., Pelaia, C., and Terracciano, R. (2020). Gingival crevicular fluid peptidome profiling in healthy and in periodontal diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155270"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"100","DOI":"10.5604\/18982395.1227565","article-title":"Assessment of bone sialoprotein in the saliva of women at peri- and postmenopausal age","volume":"10","author":"Bachanek","year":"2016","journal-title":"J. Pre-Clin. Clin. Res."},{"key":"ref_89","first-page":"ZE01","article-title":"Point of Care-A Novel Approach to Periodontal Diagnosis-A Review","volume":"11","author":"Srivastava","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_90","first-page":"e27471","article-title":"Role of saliva as a non-invasive diagnostic method for detection of COVID-19","volume":"14","author":"Ghosh","year":"2022","journal-title":"Cureus"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"930","DOI":"10.2319\/100518-719.1","article-title":"A cross-sectional cohort study of gingival crevicular fluid biomarkers in normal-weight and obese subjects during orthodontic treatment with fixed appliances","volume":"89","author":"Saloom","year":"2019","journal-title":"Angle Orthod."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Luchian, I., Goriuc, A., Sandu, D., and Covasa, M. (2022). The role of matrix metalloproteinases (MMP-8, MMP-9, MMP-13) in periodontal and peri-implant pathological processes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031806"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2147\/JIR.S177188","article-title":"Evaluation of chemokine CXCL10 in human gingival crevicular fluid, saliva, and serum as periodontitis biomarker","volume":"11","author":"Aldahlawi","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2174\/1874210601711010573","article-title":"The effect of scaling and root planning on salivary TNF-\u03b1 and IL-1\u03b1 concentrations in patients with chronic periodontitis","volume":"11","author":"Eivazi","year":"2017","journal-title":"Open Dent. J."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Kerschan-Schindl, K., Boschitsch, E., Marculescu, R., Gruber, R., and Pietschmann, P. (2020). Bone turnover markers in serum but not in saliva correlate with bone mineral density. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-68442-z"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/cncr.32644","article-title":"A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes","volume":"126","author":"Basak","year":"2020","journal-title":"Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1177\/0022034520970536","article-title":"SARS-CoV-2 detection in gingival crevicular fluid","volume":"100","author":"Gupta","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Kuo, T.-R., and Chen, C.-H. (2017). Bone biomarker for the clinical assessment of osteoporosis: Recent developments and future perspectives. Biomark. Res., 5.","DOI":"10.1186\/s40364-017-0097-4"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"115031","DOI":"10.1016\/j.bone.2019.08.004","article-title":"Osteocalcin affects bone mineral and mechanical properties in female mice","volume":"128","author":"Berezovska","year":"2019","journal-title":"Bone"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.acc.2017.06.005","article-title":"Calcium and Bone Metabolism Indices","volume":"Volume 82","author":"Makowski","year":"2017","journal-title":"Advances in Clinical Chemistry"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"450","DOI":"10.2298\/SARH1608450V","article-title":"Capture the fracture\u2013Use of bone turnover markers in clinical practice","volume":"144","author":"Vuksanovic","year":"2016","journal-title":"Srp. Arh. Celok. Lek."},{"key":"ref_102","unstructured":"Rowe, P., Koller, A., and Sharma, S. (2023). Physiology, Bone Remodeling. StatPearls, StatPearls Publishing."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Aibar-Almaz\u00e1n, A., Voltes-Mart\u00ednez, A., Castellote-Caballero, Y., Afanador-Restrepo, D.F., Carcel\u00e9n-Fraile, M.D.C., and L\u00f3pez-Ruiz, E. (2022). Current status of the diagnosis and management of osteoporosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169465"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bone.2016.10.007","article-title":"Role and mechanism of action of sclerostin in bone","volume":"96","author":"Sato","year":"2017","journal-title":"Bone"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Lin, X., Patil, S., Gao, Y.G., and Qian, A. (2020). The bone extracellular matrix in bone formation and regeneration. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00757"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/JPER.21-0611","article-title":"Association between periodontal disease, tooth extraction, and medication-related osteonecrosis of the jaw in women receiving bisphosphonates: A national cohort-based study","volume":"94","author":"Kwoen","year":"2023","journal-title":"J. Periodontol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bast\u00edas, D., Maturana, A., Mar\u00edn, C., Mart\u00ednez, R., and Niklander, S.E. (2024). Salivary biomarkers for oral cancer detection: An exploratory systematic review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052634"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13005-021-00280-4","article-title":"A pragmatic window of opportunity to minimise the risk of MRONJ development in individuals with osteoporosis on Denosumab therapy: A hypothesis","volume":"17","author":"Campisi","year":"2021","journal-title":"Head Face Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"C\u00e1rdenas, A.M., Ardila, L.J., Vernal, R., Melgar-Rodr\u00edguez, S., and Hern\u00e1ndez, H.G. (2022). Biomarkers of periodontitis and its differential DNA methylation and gene expression in immune cells: A systematic review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231912042"},{"key":"ref_110","first-page":"ZE07","article-title":"Bonebiomarkers in periodontal disease: A review article","volume":"9","author":"Ram","year":"2015","journal-title":"J. Clin. Diagn. Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/19\/2184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:07:19Z","timestamp":1760112439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/19\/2184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,30]]},"references-count":110,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["diagnostics14192184"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics14192184","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,30]]}}}