Repozitorij Medicinskog fakulteta Sveučilišta u Zagrebu

Dinamika koštanog metabolizma nakon transplantacije jetre

Jadrijević, Stipislav (2011) Dinamika koštanog metabolizma nakon transplantacije jetre. PhD thesis, Sveučilište u Zagrebu.

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    Croatian abstract

    U završnom stadiju jetrene bolesti poremećen je koštani metabolizam. Kronična bolest jetre i njoj pridružena stanja, kao što su hipogonadizam, poremećen metabolizam vitamina D, poremećen metabolizam žuči, podhranjenost, ingestija alkohola, te slabija tjelesna aktivnost dovode do gubitka koštane mase (BMD). Isto tako poznato je da je ubrzan gubitak koštane mase u ranom periodu nakon transplantacije, a to se pak objašnjava utjecajem kortikosteroida, imunosupresivnih lijekova i imobilizacije u ranom postoperativnom periodu. Gubitak koštane mase dovodi do povećanog rizika od fraktura kod transplantiranih pacijenata, a samim tim se povećava morbiditet i mortalitet kod tih pacijenata. Primarni cilj ovog rada bio je pratiti koštani metabolizam, tj dinamiku koštane razgradnje i koštane izgradnje, osteoprotegerina i statusa vitamina D u bolesnika s transplantiranom jetrom u prvoj godini nakon zahvata. Dinamiku koštanog metabolizma pratili smo kod 88 bolesnika mjerenjem biokemijskih pretraga koštane izgradnje i razgradnje, 25-hidroksivitamina D, te osteoprotegerina (molekule poveznice regulacije koštane pregradnje) u vrijeme transplantacije, te nakon 14 dana, 3, 6 i 12 mjeseci. Denzitometrija vrata bedrene kosti i slabinske kralježnice u 22 bolesnika 6 i 12 mjeseci nakon transplantacije. Rezultati mjerenja biokemijskih pretraga su pokazali ubrzanu koštanu razgradnju tijekom cijelog razdoblja praćenja, smanjenu koštanu izgradnju na temelju koncentracija osteokalcina koja se povećala i popravila u ovom razdoblju, hipovitaminozu D u cijelom razdoblju, te početno visoke koncentracije osteoprotegerina koje su se smanjile u nastavku praćenja. Ostali pokazatelji koštane izgradnje P1CP i koštana alkalna fosfataza su tijekom praćenja bile uglavnom unutar referentnog raspona. Koncentracija crosslapsa se smanjuje (p=0,005) u razdoblju od 14 dana do 12 mjeseci; osteokalcin se u odnosu na početno mjerenje povećava (p<0,02), a osteoprotegerin smanjuje (p<0,003) u svim daljnjim mjerenjima; kontinuirana hipovitaminoza 25-OH D se pogoršava 3 mjeseca nakon transplantacije (p<0,02); P1CP se smanjuje nakon 3 i 12 mjeseci (p<0,02); koštana alkalna fosfataza se povećava nakon 14 dana i 6 mjeseci (p<0,03). Koštana masa u većine bolesnika je normalna ili umjereno smanjena (osteopenija), te se popravlja (p<0,01) u području vrata bedrene kosti na kraju praćenja, ali se ne mijenja u slabinskoj kralježnici. Poremećaj koštanog metabolizma kod bolesnika u prvoj godini nakon transplantacije jetre ukazuje na izrazito usporenu koštanu izgradnju koja se popravlja ubrzo nakon tranplantacije, te postojanje umjereno povećane koštane razgradnje. Ovaj poremećaj je iskazan i promjenama osteoprotegerina, molekule regulacije aktivnosti osteoblasta i osteoklasta. Koštana masa kod ovih bolesnika je normalna ili snižena (osteopenija), te se popravlja za područje vrata bedrene kosti, ali je bez promjena u slabinskoj kralježnici.

    English abstract

    Deterioration of bone metabolism is a major complication of end-stage liver disease. Chronic liver disease and its associated conditions, including hypogonadism, disturbed vitamin D and bile metabolism, malnourishment, alcohol ingestion, and poor physical activity all lead to decrease in bone mineral density (BMD). In addition, loss of bone mass in the early post-transplant period is known to be rapid and has been ascribed to the effects of corticosteroids, immunosuppressive agents and immobilization in the early postoperative period. Bone mass deficit leads to an increased risk of fractures in transplanted patients, with concomittant increased morbidity and mortality in those patients. The primary objective of this study was to monitor bone metabolism, ie. the dynamics of bone resorption and formation, osteoprotegerin, and vitamin D status in the liver transplant patients over the course of the first year following transplantation. The dynamics of bone metabolism was investigated in the study comprised 88 patients and included measurement of biochemical parameters of bone turnover, 25- hydroxy vitamin D and osteoprotegerin (decoy ligand for osteoclast function) at transplantation, afer 14 days, 3, 6 and 12 months. Densitometry was performed at the left hip and lumbar spine in 22 patient after 6 and 12 months. Results of biochemical measurements indicated increased bone resorption during the entire follow-up period, decreased bone formation as assessed by osteocalcin which normalized, 25-OH D deficiency, and initially increased osteoprotegerin which also normalized in this period. Other bone formation markers P1CP and bone alkaline phosphatase were mostly within normal range. Crosslaps decreased after 14 days and thereafter (p=0.005), osteocalcin increased (p<0.02) and osteoprotegerin decreased (p<0.003) after initial measurements; 25-OH D deficiency further decreased after 3 months (p<0.02); P1CP decreased after 3 and 12 months (p<0.02); bone alkaline phosphatase increased after 14 days and 6 months (p<0.03). Bone mass in most patients was either normal or osteopenic, with improvement at the left hip after 12 months (p<0.01), but no change at the lumbar spine. Metabolic bone disorder in the first post-transplant year was characterised by decreased bone formation which improves almost immediately after liver transplantation, and continuosly increased bone resorption. Variations in osteoprotegerin levels corresponded to osteoblast and osteoclast cell activities. Bone mass in liver transplant recipients was normal or osteopenic, but improved only for the hip site.

    Item Type: Thesis (PhD)
    Mentor: Kušec, Vesna
    Divisions: Izvan medicinskog fakulteta
    Depositing User: Marijan Šember
    University: Sveučilište u Zagrebu
    Institution: Medicinski fakultet
    Number of Pages: 94
    Status: Unpublished
    Creators:
    CreatorsEmail
    Jadrijević, Stipislav
    Date: 20 June 2011
    Date Deposited: 09 Sep 2011
    Last Modified: 23 Sep 2011 18:12
    Subjects: /
    Related URLs:
      URI: http://medlib.mef.hr/id/eprint/1008

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