{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:53:18Z","timestamp":1791805998276,"version":"4.3.4"},"reference-count":72,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Aim. To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to conventional therapies. Methods. We performed further statistical analyses on patient data from two published, double-blind, randomized, and placebo-controlled studies (DB-RCTs), which examined the effects of intra-articular corticosteroids (ia-CSs), hyaluronic acid (ia-HA)\u2014K\u0418-109-3-0008\/14.01.2014, and intravenous bisphosphonates (iv-BPs) -K\u0418- 109-3-0009\/14.01.2014 compared to the country\u2019s standard pHOA therapy. The data span an 8-year follow-up of 700 patients with pHOA, including: 1. Clinical parameters (WOMAC-A, B, C, and T; PtGA). 2. Laboratory markers (serum calcium and phosphate levels; 25-OH-D and PTH, markers for bone sCTX-I and cartilage uCTX-II turnover). 3. Radiological indicators: X-ray stage (Kellgren-Lawrence (K\/L) and model (Bombelli\/OOARSI), width (mJSW), speed (JSN mm\/year), and zone of maximum narrowing of the joint space (max-JSN)\u2014determining the type of femoral head migration (FHM). 4. DXA indicators: bone geometry (HAL; NSA; and MNW); changes in regional and total bone mineral density (TH-BMD, LS-BMD, and TB-BMD). 5. Therapeutic responses (OARSI\/MCII; mJSW; JSNmm\/yearly) to different drug regimens (iv-BP -zoledronic acid (ZA\/-5 mg\/yearly for 3 years)); ia-CS 40 mg methylprednisolone acetate, twice every 6 months; and ia-HA with intermediate molecular weight (20 mg\/2 mL \u00d7 3 weekly applications, two courses every 6 months) were compared to standard of care therapy (Standard of Care\/SC\/), namely D3-supplementation according to serum levels (20\u2013120 ng\/mL; target level of 60 ng\/mL), simple analgesics (paracetamol, up to 2.0 g\/24 h), and physical exercises. The abovementioned data were integrated into a non-supervised hierarchical agglomerative clustering analysis (NHACA) using Ward\u2019s linkage method and the squared Euclidean distance to identify different endophenotypes (EFs). Univariate and multivariate multinomial logistic regression analyses were performed to determine the impact of sex and FHM on clinical and radiographic regression of pHOA. Results. A baseline cluster analysis using incoming (M0) patient data identified three EFs: hypertrophic H-HOA, atrophic A-HOA, and intermediate I-HOA. These EFs had characteristics that were similar to those of patients grouped by radiographic stage and pattern (\u2018H\u2019-RPs, \u2018I\u2019-RPs, and \u2018A\u2019-RPs), p &lt; 0.05). The repeated cluster analysis of M36 data identified four EF pHOAs: 1. Hypertrophic (slow progressors, the influence of the type of femoral head migration (FHM) outweighing the influence of sex on progression), progressing to planned total hip replacement (THR) within 5 (K\/LIII) to 10 (K\/LII) years. 2. Intermediate (sex is more important than the FHM type for progression) with two subgroups: 2#: male-associated (slow progressors), THR within 4 (K\/LIII) to 8 years. (K\/LII). 2* Female-associated (rapid progressors), THR within 3 (K\/LIII) to 5 (K\/LII) years. 3. Atrophic (rapid progressors; the influence of FHM type outweighs that of sex), THR within 2 (K\/LIII) to 4 (K\/LII) years. Each EF, in addition to the patient\u2019s individual progression rate, was also associated with a different response to the aforementioned therapies. Conclusions. Clinical endophenotyping provides guidance for a personalized approach in patients with pHOA, simultaneously assisting the creation of homogeneous patient groups necessary for conducting modern genetic and therapeutic scientific studies.<\/jats:p>","DOI":"10.3390\/life14050622","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Endophenotypes of Primary Osteoarthritis of the Hip Joint in the Bulgarian Population over 60 Years Old"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-3532","authenticated-orcid":false,"given":"Lyubomir","family":"Sapundzhiev","sequence":"first","affiliation":[{"name":"Department of Propedeutics of Internal Diseases, Medical Faculty, Medical University of Plovdiv, 4001 Plovdiv, Bulgaria"},{"name":"Rheumatology Department, University Hospital \u2018Pulmed\u2019 Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Sapundzhieva","sequence":"additional","affiliation":[{"name":"Department of Propedeutics of Internal Diseases, Medical Faculty, Medical University of Plovdiv, 4001 Plovdiv, Bulgaria"},{"name":"Rheumatology Department, University Hospital \u2018Pulmed\u2019 Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-4284","authenticated-orcid":false,"given":"Kamen","family":"Klinkanov","sequence":"additional","affiliation":[{"name":"Department of Propedeutics of Internal Diseases, Medical Faculty, Medical University of Plovdiv, 4001 Plovdiv, Bulgaria"},{"name":"Rheumatology Department, University Hospital \u2018Pulmed\u2019 Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Mitev","sequence":"additional","affiliation":[{"name":"Rheumatology Department, University Hospital \u2018Pulmed\u2019 Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2564-3291","authenticated-orcid":false,"given":"Kiril","family":"Simitchiev","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Computer Chemistry, Faculty of Chemistry, University of Plovdiv, 4001 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8857-0574","authenticated-orcid":false,"given":"Anastas","family":"Batalov","sequence":"additional","affiliation":[{"name":"Department of Propedeutics of Internal Diseases, Medical Faculty, Medical University of Plovdiv, 4001 Plovdiv, Bulgaria"},{"name":"Rheumatology Clinic, University Hospital \u2018Kaspela\u2019, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","first-page":"21","article-title":"Osteoarthritis\u2014A modern concept of etiology and pathogenesis\u2014Review article","volume":"29","author":"Sapundzhiev","year":"2021","journal-title":"Rheumatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.joca.2010.01.007","article-title":"Identifying different osteoarthritis phenotypes through epidemiology","volume":"18","author":"Felson","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"iv34","DOI":"10.1093\/rheumatology\/kex417","article-title":"Is osteoarthritis one disease or a collection of many?","volume":"57","author":"Deveza","year":"2018","journal-title":"Rheumatology"},{"key":"ref_5","first-page":"64","article-title":"Phenotypes of osteoarthritis: Current state and future implications","volume":"37","author":"Deveza","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/annrheumdis-2018-213864","article-title":"Deep phenotyping of osteoarthritis: A step forward","volume":"78","author":"Berenbaum","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","unstructured":"(2010, January 13). Phenotype, Oxford English Dictionary. Available online: http:\/\/dictionary.oed.com."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dell\u2019Isola, A., and Steultjens, M. (2018). Classification of patients with knee osteoarthritis in clinical phenotypes: Data from the osteoarthritis initiative. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191045"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bcp.2019.02.037","article-title":"Osteoarthritis phenotypes and novel therapeutic targets","volume":"165","author":"Kubassova","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.joca.2021.11.001","article-title":"Osteoarthritis in year 2021: Biochemical markers","volume":"30","author":"Henrotin","year":"2022","journal-title":"Osteoarthr. Cartil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1136\/annrheumdis-2020-217834","article-title":"Uitterlinden AGGenome-wide association of phenotypes based on clustering patterns of hand osteoarthritis identify WNT9A as novel osteoarthritis gene","volume":"80","author":"Boer","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1002\/acr.25047","article-title":"Identification of Symptom Phenotypes of Hand Osteoarthritis Using Hierarchical Clustering: Results From the DIGICOD Cohort","volume":"75","author":"Binvignat","year":"2023","journal-title":"Arthritis Care Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1136\/ard.41.2.118","article-title":"Osteoarthritis of the hip: The patient behind the disease","volume":"41","author":"Solomon","year":"1982","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bombelli, R. (1983). Osteoarthritis of the Hip: Classification and Pathogenesis, Springer. [2nd ed.].","DOI":"10.1007\/978-3-642-96691-0"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/ard.51.10.1111","article-title":"Radiographic patterns and associations of osteoarthritis of the hip","volume":"51","author":"Ledingham","year":"1992","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1136\/ard.52.4.263","article-title":"Radiographic progression of hospital referred osteoarthritis of the hip","volume":"52","author":"Ledingham","year":"1993","journal-title":"Ann. Rheum. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1136\/ard.2002.003780","article-title":"Influence of radiographic phenotype on risk of hip osteoarthritis within families","volume":"63","author":"Lanyon","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/ard.55.6.356","article-title":"Radiological progression of hip osteoarthritis: Definition, risk factors and correlations with clinical status","volume":"55","author":"Dougados","year":"1996","journal-title":"Ann. Rheum. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/art.10660","article-title":"Prognostic factors of progress of hip osteoarthritis: A systematic review","volume":"47","author":"Lievense","year":"2002","journal-title":"Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/art.24641","article-title":"Variables associated with the progression of hip osteoarthritis: A systematic review","volume":"61","author":"Wright","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s13075-019-1969-9","article-title":"Prognostic factors for progression of osteoarthritis of the hip: A systematic review","volume":"21","author":"Teirlinck","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_22","first-page":"403","article-title":"Epidemiological, clinical, biological and radiological differences between atrophic and hypertrophic patterns of hip osteoarthritis: A case-control study","volume":"22","author":"Conrozier","year":"2004","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.joca.2006.09.002","article-title":"Differences in biomarkers of type II collagen in atrophic and hypertrophic osteoarthritis of the hip: Implications for the differing pathobiologies","volume":"15","author":"Conrozier","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.joca.2017.01.006","article-title":"Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients","volume":"25","author":"Arends","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.joca.2018.12.001","article-title":"Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients","volume":"27","author":"Karsdal","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R162","DOI":"10.1186\/ar2845","article-title":"Dual energy X-ray absorptiometry analysis contributes to the prediction of hip osteoarthritis progression","volume":"11","author":"Betancourt","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/art.37792","article-title":"Bone parameters across different types of hip osteoarthritis and their relationship to osteoporotic fracture risk","volume":"65","author":"Rivadeneira","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/art.40735","article-title":"Are Bone Mineral Density and Fractures Related to the Incidence and Progression of Radiographic Osteoarthritis of the Knee, Hip, and Hand in Elderly Men and Women? The Rotterdam Study","volume":"71","author":"Bergink","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"ref_29","first-page":"156","article-title":"Intra-articular injection for pain relief in patients awaiting hip replacement","volume":"70","author":"Flanagan","year":"1988","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/ard.56.8.476","article-title":"Radiographic patterns and response to corticosteroid hip injection","volume":"56","author":"Plant","year":"1997","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","first-page":"100","article-title":"Impact of the Indicator \u2018Radiographic Pattern\u2019 on the Clinical Presentation and Radiographic Progression of Hip Osteoarthritis\u2014Results from an 8-Year Study","volume":"9","author":"Sapundzhiev","year":"2023","journal-title":"J. Rheum. Dis. Treat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1136\/annrheumdis-2013-204111","article-title":"The coupling of bone and cartilage turnover in osteoarthritis: Opportunities for bone antiresorptives and anabolics as potential treatments?","volume":"73","author":"Karsdal","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1007\/s10067-013-2338-8","article-title":"Alendronate treatment for hip osteoarthritis: Prospective randomized 2-year trial","volume":"32","author":"Nishii","year":"2013","journal-title":"Clin. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sapundzhiev, L., Sapundzhieva, T., Mitev, M., Simitchiev, K., and Batalov, A. (2023). Correlation between Bone Mineral Density and Progression of Hip Osteoarthritis in Adult Men and Women in Bulgaria-Results from a 7-Year Study. Life, 13.","DOI":"10.3390\/life13020421"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1136\/annrheumdis-2016-210373","article-title":"Radiographic endophenotyping in hip osteoarthritis improves the precision of genetic association analysis","volume":"76","author":"Panoutsopoulou","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/art.1780340502","article-title":"The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip","volume":"34","author":"Altman","year":"1991","journal-title":"Arthritis Rheum."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S240","DOI":"10.1002\/acr.20543","article-title":"Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP)","volume":"63","author":"Hawker","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_38","first-page":"1833","article-title":"Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee","volume":"15","author":"Bellamy","year":"1988","journal-title":"J. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1136\/ard.16.4.494","article-title":"Radiological assessment of osteo-arthrosis","volume":"16","author":"Kellgren","year":"1957","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.joca.2015.03.006","article-title":"OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hip osteoarthritis","volume":"23","author":"Lane","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s11657-013-0133-4","article-title":"Vitamin D status in Bulgaria\u2014Winter data","volume":"8","author":"Borissova","year":"2013","journal-title":"Arch. Osteoporos."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11657-011-0064-x","article-title":"Femoral neck bone mineral density and 10-year absolute fracture risk in a national representative sample of Bulgarian women aged 50 years and older","volume":"6","author":"Borissova","year":"2011","journal-title":"Arch. Osteoporos."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"57622","DOI":"10.52965\/001c.57622","article-title":"Prevalence of low bone mineral density at axial sites and fracture risk in Bulgarian population","volume":"14","author":"Kirilova","year":"2022","journal-title":"Orthop. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.joca.2004.02.001","article-title":"OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited","volume":"12","author":"Pham","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/ard.2004.022905","article-title":"Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: The minimal clinically important improvement","volume":"64","author":"Tubach","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S217","DOI":"10.1097\/00005650-198903001-00018","article-title":"Generic and disease-specific measures in assessing health status and quality of life","volume":"27","author":"Patrick","year":"1989","journal-title":"Med. Care"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1515\/CCLM.2011.602","article-title":"International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis","volume":"49","author":"Vasikaran","year":"2011","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.cca.2016.10.016","article-title":"Perspective and priorities for improvement of parathyroid hormone (PTH) measurement\u2014A view from the IFCC Working Group for PTH","volume":"467","author":"Sturgeon","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"R19","DOI":"10.1530\/EJE-17-0585","article-title":"Diagnosis of Endocrine Disease: Bone turnover markers: Are they clinically useful?","volume":"178","author":"Eastell","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.joca.2010.01.012","article-title":"Serum and urinary biochemical markers for knee and hip-osteoarthritis: A systematic review applying the consensus BIPED criteria","volume":"18","author":"DeGroot","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.joca.2019.12.012","article-title":"The cartilage degradation marker, urinary CTX-II, is associated with the risk of incident total joint replacement in postmenopausal women. A 18 year evaluation of the OFELY prospective cohort","volume":"28","author":"Garnero","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.jocd.2015.06.013","article-title":"Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD","volume":"18","author":"Shepherd","year":"2015","journal-title":"J. Clin. Densitom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.joca.2004.04.004","article-title":"Measurement of structural progression in osteoarthritis of the hip: The Barcelona consensus group","volume":"12","author":"Altman","year":"2004","journal-title":"Osteoarthr. Cartil."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.joca.2015.03.004","article-title":"OARSI Clinical Trials Recommendations: Hip imaging in clinical trials in osteoarthritis","volume":"23","author":"Gold","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"A1","DOI":"10.1016\/j.joca.2006.11.009","article-title":"Atlas of individual radiographic features in osteoarthritis, revised","volume":"15","author":"Altman","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Nielsen, F. (2016). Introduction to HPC with MPI for Data Science. Undergraduate Topics in Computer Science, Springer.","DOI":"10.1007\/978-3-319-21903-5"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10115-012-0522-9","article-title":"Overlapping correlation clustering","volume":"35","author":"Bonchi","year":"2013","journal-title":"Knowl. Inf. Syst."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF02294245","article-title":"An examination of procedures for determining the number of clusters in a data set","volume":"50","author":"Milligan","year":"1985","journal-title":"Psychometrika"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/1467-9868.00293","article-title":"Estimating the number of clusters in a data set via the gap statistic","volume":"63","author":"Tibshirani","year":"2001","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.csda.2006.11.025","article-title":"Cluster-wise assessment of cluster stability","volume":"52","author":"Hennig","year":"2007","journal-title":"Comput. Stat. Data Anal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/biom.12647","article-title":"Statistical significance for hierarchical clustering","volume":"73","author":"Kimes","year":"2017","journal-title":"Biometrics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/biomet\/75.2.383","article-title":"A stagewise rejective multiple test procedure based on a modified Bonferroni test","volume":"75","author":"Hommel","year":"1988","journal-title":"Biometrika"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1136\/annrheumdis-2018-214827","article-title":"Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): A randomised, double-blind, placebocontrolled phase 3 trial","volume":"78","author":"Takeuchi","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tanaka, Y. (2021). Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061241"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1759720X20906040","article-title":"Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review","volume":"12","author":"Baraliakos","year":"2020","journal-title":"Ther. Adv. Musculoskel. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.arth.2023.09.003","article-title":"2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective","volume":"38","author":"Hannon","year":"2023","journal-title":"J. Arthroplast."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/acr.24131","article-title":"2019 American College of Rheumatology\/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.joca.2005.09.007","article-title":"Intra-articular treatment of hip osteoarthritis: A randomized trial of hyaluronic acid, corticosteroid, and isotonic saline","volume":"14","author":"Qvistgaard","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/ard.2009.127183","article-title":"Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis","volume":"70","author":"Atchia","year":"2011","journal-title":"Ann. Rheum. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/art.24301","article-title":"Effect of hyaluronic acid in symptomatic hip osteoarthritis. A multicenter, randomized, placebo-controlled trial","volume":"60","author":"Richette","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.joca.2018.08.018","article-title":"Evaluation of use of intraarticular injection as a treatment for painful hip osteoarthritis: A randomized, double-blindq multicenter, parallel group study comparing a single 6-ml injection of hylan GF-20 with saline","volume":"27","author":"Brander","year":"2019","journal-title":"Osteoarthr. Cartil."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/5\/622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:56Z","timestamp":1760107256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/5\/622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,11]]},"references-count":72,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["life14050622"],"URL":"https:\/\/doi.org\/10.3390\/life14050622","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,11]]}}}