Povezanost dolžine telomer v levkocitih z mineralno kostno gostoto in kvaliteto trabekularne kosti pri pomenopavznih ženskah

Rojnik, Tamara (author), Ostanek, Barbara (mentor)

Osteoporoza je najpogostejša presnovna bolezen kosti, ki zaradi staranja svetovnega prebivalstva predstavlja vedno večje zdravstveno in socialno-ekonomsko breme. Nastane zaradi neravnovesja med resorpcijo in tvorbo kosti, ki se klinično kaže kot zmanjšana mineralna kostna gostota in porušena mikroarhitektura kosti. Posledica krhkih kosti je zlom, ki je povezan z večjo smrtnostjo in slabšo kakovostjo življenja. Z današnjimi pristopi diagnosticiranja in zdravljenja osteoporoze, spregledamo velik del bolnic, ki so izpostavljene večjemu tveganju za zlome. Merjenje dolžine telomer v levkocitih predstavlja novo potencialno orodje, ki bi lahko dopolnjevalo obstoječe metode. Telomere so zaščitni konci kromosomov, ki se z vsako delitvijo celice krajšajo. Zato veljajo za biološki kazalec staranja ter jih povezujemo s starostnimi boleznimi, med katere sodi tudi osteoporoza. V magistrski nalogi smo preučevali povezavo med dolžino telomer v levkocitih z mineralno kostno gostoto in kvaliteto trabekularne kosti pri pomenopavznih ženskah. V ta namen smo deoksiribonukleinsko kislino izolirali iz polne krvi in levkocitnega koncentrata, relativno dolžino telomer v levkocitih izmerili s pomočjo verižne reakcije s polimerazo v realnem času in s statistično analizo preverili povezavo med dolžino telomer in mineralno kostno gostoto ter kazalcem kvalitete trabekularne kosti. Kljub negativnemu trendu med dolžino telomer in kazalcem kvalitete trabekularne kosti ter pozitivnemu trendu med dolžino telomer in mineralno kostno gostoto (kolk, ledvena vretenca, podlaht, 1/3 radius) je povezava bila statistično neznačilna. Čeprav trend kaže, da so osteoporozne ženske imele v povprečju krajše telomere, je bila razlika v dolžini telomer v primerjavi s kontrolno skupino z in brez upoštevanjem starosti in indeksa telesne mase, statistično neznačilna. Statistično neznačilna z upoštevanjem kovariat je ostala tudi razlika v dolžini telomer med ženskami z degradirano in normalno kostno mikroarhitekturo s tem, da trend kaže, da so slednje imele v povprečju krajše telomere. Zaključimo lahko, da povezave med dolžino telomer v levkocitih in mineralno kostno gostoto ter kazalcem kvalitete trabekularne kosti na vzorcu 60 slovenskih pomenopavznih žensk nismo dokazali. Naša raziskava je prva preverjala povezavo med dolžino telomer v levkocitih in kazalcem kvalitete trabekularne kosti. Da bi lahko bolje ovrednotili ali krajšanje telomer v levkocitih odraža krhkost kosti, bi bilo potrebno izvesti velike longitudinalne študije, kjer bi med drugim spremljali tudi povezavo med dolžino telomer v levkocitih in osteoporoznimi zlomi.

• Language: Slovenian
• Keywords: Osteoporoza, dolžina telomer v levkocitih, verižna reakcija s polimerazo v realnem času, mineralna kostna gostota, kazalec kakovosti trabekularne kosti.
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2019
• PID: 20.500.12556/RUL-110659
• Publication date in RUL: 18.09.2019

Secondary language

• Language: English
• Title: The association of leukocyte telomere length with bone mineral density and trabecular bone score of postmenopausal women

Abstract

Osteoporosis is the most common metabolic bone disease, which, due to the aging of the world's population, represents an increasing health and socio-economic burden. It is caused by an imbalance between bone resorption and formation, that is clinically characterized as a reduced bone mineral density and microarchitectural deterioration of bone tissue. Brittle bones lead to fractures and consequently to higher mortality rate and diminished quality of life. Current approaches to diagnosis and treatment of osteoporosis overlook a large proportion of patients, who are at greater risk of fractures. Assessment of leukocyte telomere length represents a new potential tool, that could complement existing methods. Telomeres are protective ends of chromosomes, which shorten with every cell division. Therefore, they are considered as a biomarker of aging and are associated with age-related diseases, including osteoporosis. In our research we studied the association of leukocyte telomere length with bone mineral density and quality of trabecular bone of postmenopausal women. With this intention we have first isolated the deoxyribonucleic acid from whole blood and buffy coat, then we measured relative leukocyte telomere length using real-time polymerase chain reaction and at the end we statistically analyzed association of telomere length with bone mineral density and trabecular bone score. Despite the apparent negative trend between telomere length and trabecular bone score and despite positive trend between telomere length and bone mineral density (hip, spine, forearm, 1/3 radius), no statistically significant association could be demonstrated. Although women with osteoporosis showed trend of shorter telomere length, the difference in telomere length compared to control group with or without age and body mass index adjustments remained statistically insignificant. After adjusting for covariants the difference in telomere length between women with degraded bone microarchitecture and healthy subjects remained statistically insignificant. The latter showed trend of shorter telomeres. To conclude, we could not prove association of leukocyte telomere length with bone mineral density and trabecular bone score in studied group of 60 Slovenian postmenopausal women. Our research was the first which examined the association of leukocyte telomere length and trabecular bone score. Large longitudinal studies, in which the association of leukocytes telomere length with osteoporotic fractures would be investigated are warranted to better elucidate the relevance of leukocyte telomere length in bone fragility.

• Keywords: Osteoporosis, leukocyte telomere length, real-time polymerase chain reaction, bone mineral density, trabecular bone score.