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Effect of tumor necrosis factor inhibitor therapy on bone mineral density and biochemical markers in bone - procollagen type 1 Nterminal propeptide and beta-crosslaps in female patients suffering from rheumatoid arthritis

dc.contributor.advisorMikov, Momir
dc.contributor.advisorPopović, Đorđe
dc.contributor.otherTomašević-Todorović, Snežana
dc.contributor.otherVasović, Velibor
dc.contributor.otherGlišić, Branislav
dc.contributor.otherMikov, Momir
dc.contributor.otherPopović, Đorđe
dc.creatorJanković, Tanja
dc.date.accessioned2020-07-06T13:28:31Z
dc.date.available2020-06-23T13:28:31Z
dc.date.available2020-07-03T13:28:37Z
dc.date.issued2020-05-13
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija157407590841813.pdf?controlNumber=(BISIS)112400&fileName=157407590841813.pdf&id=14260&source=NaRDuS&language=srsr
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/12334
dc.identifier.urihttps://www.cris.uns.ac.rs/record.jsf?recordId=112400&source=NaRDuS&language=srsr
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije157407592693222.pdf?controlNumber=(BISIS)112400&fileName=157407592693222.pdf&id=14261&source=NaRDuS&language=srsr
dc.description.abstractReumatoidni artritis (RA) je hronično inflamatorno oboljenje zglobova koji nastaje usled poremećaja u regulaciji imunskih mehanizama. TNF-alfa jedan je od ključnih medijatora inflamacije u RA, a koji preko složenih mehanizama podstiče aktivnost osteoklasta koji dovodi do poremećaja u procesu koštanog remodelovanja u pravcu povećane koštane resorpcije koji se klinički može pratiti određivanjem nivoa markera koštane resorpcije i koštanog formiranja u urinu i serumu. Primenom TNF inhibitora započeo je novi koncept lečenja RA. Cilj rada: Utvrditi razliku mineralne koštane gustine (BMDg/cm2) i vrednosti koštanih biohemijskih markera-prokolagen tip 1N-terminalni propeptid (P1NP) i beta-crosslapsa pre uvođenja terapije, i nakon godinu dana sprovedene terapije TNF inhibitorima. Metode: Studija je sprovedena u Specijalnoj bolnici za reumatske bolesti Novi Sad jednim delom kao retrospektivno, a drugim delom prospektivno istraživanje, koje je obuhvatilo 50 bolesnica sa dijagnozom reumatoidnog artritisa kod kojih je postojala indikacija za uvođenje lekova iz grupe TNF inhibitora. Da bi ušle u studiju bolesnice su morale da ispune određene uključne/isključne kriterijume koji su bili vezani za dužinu trajanja RA i menopauze, način lečenja RA, stepen oštećenja zglobova i prisutnost drugih oboljenja sa reperkusijom na koštano tkivo. Pored reumatološkog i fizikalnog pregleda određivani su faktori rizika za osteoporozu i prelome. Na početku i na kraju godinu dana po uvođenju terapije TNF inhibitora rađena je osteodenzitometrija na aparatu tipa „Lunar“ merena na lumbalnoj kičmi i kuku kao i određivanje biohemijskih markera u serumu prokolagen tip 1 N-terminalni propeptid (P1NP) i betacrosslapsa ECLIA metodom. Rezultati: Prosečna starost bolesnica bila je 51,5 godina koje su u 84%, bolovale od RA do 5 godina kod kojih je u najvećem procentu dužina trajanja menopauze bila do dve godine, a u svojoj terapiji pored metotreksata su imale uključen TNF inhibitor, Etanercept 34%, Adalimubam 46%, Golimubam 9% i 2% Infliksimab.Pre uvođenja biološke terapije najveći broj bolesnica 80% imalo je osteopeniju, 14% normalan nalaz, dok je osteoporoza zabeležena kod 6% bolesnica. Na kraju jednogodišnje primene TNF inhibitora 18% bolesnica je imalo normalan osteodenzitometrijski nalaz, 78 % osteopeniji, a 4% osteoporozu. Ova promena je statistički značajna ( p=0,000). Nakon jednogodišnje primene TNF inhibitora nije došlo do smanjenja vrednosti BMD (g/cm²) merenog na lumbalnom delu kičme i kuka. Beleži se statističko značajno povećanje vrednosti T- skora (SD) merenog na lumbalnom delu kičme i vratu butne kosti. Vrednost koštanih biohemijskih markera P1NP i beta crosslapsa značajno su povećani nakon jednogodišnje primene TNF inhibitora, pri čemu se beleži veće povećanje biohemijskog markera koštane sinteze, P1NP. Zaključak: Savremeni pristup lečenja reumatoidnog artritisa podrazumeva primenu bioloških lekova kao što su TNF inhibitori koji značajno suzbijaju inflamaciju i dovode do smanjenja odnosa RANKL/OPG sistema, čime se inhibira dejstvo osteoklasta i sprečava gubitak mineralne koštane gustine. Primena TNF inhibitora nakon godinu dana sprečila je pad vrednosti BMD (g/cm²), povećana je vrednost T- skora (SD) i vrednosti koštanih biohemijskih markera, posebno markera koštane sinteze. Uprkos velikom broju studija vezanih za dejstvo TNF inhibitora na kost, za sada nema dovoljan broj istraživanja o njegovom uticaju na sprečavanju osteoporoze i preloma kostiju i nivou vrednosti koštanih biohemijskih markera posebno u dužem periodu praćenja, što će biti verovatno predmet daljih istraživanja.sr
dc.description.abstractRheumatoid arthritis (RA) is a chronic inflammatory joint disease resulting from compromised regulation of immune mechanisms. TNF-alpha is one of the key inflammation mediators in RA that, through complex mechanisms stimulates osteoclast activity, thereby modifying the bone remodeling process in the direction of increased bone resorption that can be clinically monitored by determining the level of bone resorption and bone formation markers in urine and serum. Use of TNF has initiated a new concept in RA treatment. Aims: To determine the differences in bone mineral density (BMD, g/cm2) and values of biochemical markers in bone procollagentype 1 N-terminal propeptide(P1NP) and betacrosslaps before and after yearlong TNF inhibitor therapy. Methods: The study was conducted at the Special Hospital for Rheumatic Diseases Novi Sad partly as retrospective and partly as prospective research, which involved 50 female patients diagnosed with rheumatoid arthritis in whom introduction of medications from the TNF inhibitor group was indicated. To be included in the study, patients had to meet certain inclusion/exclusion criteria related to RA and menopause duration, RA treatment, degree of joint impairment, and presence of comorbidities with repercussions for bone tissues. In addition to rheumatological and physical examinations, risk factors for osteoporosis and fractures were determined. At the beginning and one year after commencing TNF inhibitor therapy, osteodensitometry was performed using “Lunar” apparatus, taking measurements on lumbar spine and hip, and serum levels of biochemical markers procollagentype 1 Nterminal propeptide(P1NP) and beta-crosslaps were determined via ECLIA method. Results: Mean patient age was 51.5 years, 84% of whom suffered from RA for up to 5 years, and in the greatest percentage experienced menopause for two years, receiving therapy that in addition to methotrexate included a TNF inhibitor, Etanercept 34%, Adalimumab 46%, Golimumab 9%, and 2% Infliximab. Prior to commencing biological therapy, majority of patients 80% suffered from osteopenia, 14% had normal findings, and osteoporosis was recorded in 6% of patients. At the end of yearlong TNF inhibitor therapy, 18% of patients had normal osteodensitometry findings, 78% had osteopenia and 4% osteoporosis. This change was statistically significant (p = 0.000). As a result of yearlong TNF inhibitor therapy no reduction occurred in BMD (g/cm²) values in lumbar spine and hip. Statistically significantly higher T scores (SD) pertaining to lumbar spine and femur were measured. Values of biochemical markers P1NP and beta-crosslaps significantly improved after yearlong TNF inhibitor therapy, whereby a greater increase was recorded in the biochemical bone synthesis marker, P1NP. Conclusion: Advanced rheumatoid arthritis treatment involves the use of biological compounds such as TNF inhibitors that significantly suppress inflammation and reduce the RANKL/OPG ratio, thereby inhibiting osteoclast activity and preventing bone mineral loss. TNF inhibitor therapy after one year prevented reduction in the BMD (g/cm²) levels, while increasing the T score (SD) and bone biochemical marker values, bone synthesis marker in particular. Despite a large number of studies related to the TNF inhibitor effect on bone, there is presently not enough research on its influence on osteoporosis and bone fracture prevention and bone biochemical marker levels, especially over longer periods, which will likely be the topic of further research.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Новом Садуsr
dc.subjectreumatoidni artritis; faktor tumorske nekroze-alfa + antagonisti i inhibitori; koštana gustina; biomarkeri; koštano remodelovanje; menopauza; osteoporoza; ishod lečenjasr
dc.subjectArthritis, Rheumatoid; Tumor Necrosis Factor-alpha + antagonists and inhibitors; Bone Density; Biomarkers; Bone Remodeling; Menopause; Osteoporosis; Treatment Outcomeen
dc.titleUticaj terapije inhibitora faktora tumorske nekroze na mineralnu koštanu gustinu i koštane biohemijske markere-prokolagen tip 1N-terminalni propeptid i beta-crosslaps kod bolesnica sa reumatoidnim artritisomsr
dc.title.alternativeEffect of tumor necrosis factor inhibitor therapy on bone mineral density and biochemical markers in bone - procollagen type 1 Nterminal propeptide and beta-crosslaps in female patients suffering from rheumatoid arthritisen
dc.typedoctoralThesissr
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/35501/IzvestajKomisije.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/35500/Disertacija.pdf


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