Tesis

Korelasi Kadar Serum Sklerostin dan Tumor Necrosis Factor-α (TNF-α) dengan Penanda Turnover Tulang pada Pasien Artritis Reumatoid Perempuan Premenopause = Correlation of Sclerostin and Tumor Necrosis Factor-α (TNF-α) in Bone Turnover Process of Premenopausal Women with Rheumatoid Arthritis.

Latar Belakang: Artritis reumatoid (AR) dapat menyebabkan penurunan massa tulang sistemik. TNF-α adalah sitokin utama pada AR yang dapat meningkatkan osteoklastogenesis dan diduga juga menghambat osteoblastogenesis. Hambatan osteoblastogenesis salah satunya melalui peningkatan sklerostin yang menyebabkan penghambatan jalur Wingless (Wnt) -b catenin canonical dan bone morphogenetic proteins (BMP). Sampai saat ini masih belum ada penelitian tentang korelasi TNF-a dan sklerostin terhadap penanda turnover tulang (CTX dan P1NP) pada pasien AR perempuan premenopause. Tujuan: Penelitian ini bertujuan untuk menjelaskan patogenesis hilangnya massa tulang pada pasien artritis rheumatoid perempuan premenopause dengan menilai hubungan antara kadar sitokin proinflamasi TNF-α, penghambat Wnt signaling sklerostin, dan penanda resorpsi tulang P1NP dan CTX. Metode: Studi potong lintang ini melibatkan 38 perempuan artritis reumatoid premenopause. Pengambilan sampel dilakukan secara konsekutif. Pemeriksaan TNF-α, sklerostin, CTX dan P1NP dilakukan dengan metode ELISA. Hasil: Sebanyak 38 sampel diikutsertakan dalam penelitian ini. Ditemukan kadar CTX (rerata 2,74 ng/ml) yang lebih tinggi dan P1NP (median 34,04 pg/ml) yang lebih rendah dibandingkan dengan sampel sehat pada penelitian sebelumnya. Terdapat korelasi negatif (r = -0,388) antara kadar TNF-α dengan kadar sklerostin yang bermakna secara statistik (p = 0,016). Terdapat pula korelasi positif (r = 0,362) antara kadar TNF-α dengan kadar P1NP yang bermakna secara statistik (p = 0,026). Penelitian ini tidak menemukan korelasi bermakna antara variabel lainnya pada pasien artritis reumatoid perempuan premenopause. Kesimpulan: Pada penelitian ini didapatkan adanya peningkatan CTX dan penurunan P1NP, adanya korelasi negatif bermakna antara kadar TNF-α dan sklerostin serta adanya korelasi positif bermakna antara kadar TNF-α dan P1NP, namun tidak didapatkan korelasi bermakna antara penanda lainnya.
Kata kunci: Artritis Reumatoid, TNF-α, sklerostin, turnover tulang, CTX, P1NP, premenopause


Background: Rheumatoid arthritis is associated with systemic bone mass loss. TNF-α is the main proinflammatory cytokine that is known to stimulate osteoclastogenesis and might inhibit osteoblastogenesis. One of the mechanisms of TNF-α osteoblastogenic inhibition is through increasing of sclerostin that causes inhibition of Wingless (Wnt) )-b catenin canonical and bone morphogenetic proteins (BMP) pathway. However, there are currently no studies that assess the correlation of TNF-α and sclerostin with bone turnover marker (CTX and P1NP) in premenopause rheumatoid arthritis patients. Objective: This study aims to explain the pathogenesis of bone mass decrease in premenopausal woman with rheumatoid arthritis by assessing the correlation between proinflammatory cytokine TNF-α, sclerostin, and bone resorption markers P1NP and CTX. Methods: This cross-sectional study involves 38 premenopausal women with AR. Sampling is done consecutively. TNF-α, sclerostin, CTX and P1NP measurement was done using ELISA Results: A total of 38 premenopausal women with rheumatoid arthritis participated in this study. This study found higher level of serum CTX (mean 2,74 ng/mL) and lower level of P1NP (median 34,04 pg/mL) than normal population in previous studies. There was a negative correlation (r = -0,388) between TNF-α levels and sclerostin levels which was significant (p = 0,016). There was also a positive correlation (r = 0,362) between TNF-α levels and P1NP levels which was also significant (p = 0,026). There were no significant correlation between the other variables on premenopausal women with rheumatoid arthritis. Conclusions: This study found an increase in CTX and decrease in P1NP. There was a significant negative correlation between TNF-α and sclerostin levels and also a significant positive correlation between TNF-α and P1NP levels, but there were no other significant correlation between other variables.
Key words: Rheumatoid Arthritis, TNF-α, sclerostin, bone turnover, CTX, P1NP, premenopause.