TESIS
KADAR INTERLEUKIN-6 (IL-6) YANG TINGGI SEBAGAI PENANDA TERJADINYA OSTEOARTHRITIS LUMBAL PENDERITA NYERI PINGGANG BAWAH BERUMUR DIATAS 55 TAHUN
Dewa Gede Kurnia Pratama
PEMBIMBING : Prof.DR.dr Putu Astawa, SpOT, M.Kes dr I Ketut Suyasa, SpB, SpOT (K)
PROGRAM PASCASARJANA UNIVERSITAS UDAYANA DENPASAR 2015
ABSTRAK
KADAR INTERLEUKIN-6 (IL-6) YANG TINGGI SEBAGAI PENANDA TERJADINYA OSTEOARTHRITIS LUMBAL PENDERITA NYERI PINGGANG BAWAH BERUMUR DIATAS 55 TAHUN
Nyeri pinggang bawah merupakan masalah bagi setiap klinisi.Adapun penyebab dan faktor-faktor risikonya masih belum diketahui secara pasti hingga saat ini. Oleh karena itu masih banyak studi yang meneliti berbagai penyebab dan faktor risiko nyeri pinggang sehingga berguna nantinya didalam penanganannya. Sitokin mempunyai peranan yang penting di dalam degenerasi tulang rawan sendi. Salah satunya adalah Interleukin-6 (IL-6). Namun peranan IL-6 pada OA masih merupakan kontroversi.Tujuan penelitian ini adalah mengetahui probabilitas antara faktor inflamasi interleukin-6 (IL-6) yang tinggi dengan kejadian OA lumbal pada penderita nyeri pinggang bawah yang berumur diatas 55 tahun. Rancangan penelitian ini adalah rancangan studi kasus kontrol (case control).Sampel adalah laki-laki dan perempuan yang berumur diatas 55 tahun dengan keluhan nyeri pinggang bawah sebesar 24 sampel untuk masing-masing kelompok. Kelompok kasus adalah 10 orang laki-laki dan 14 orang perempuan dengan OA lumbal, dan kelompok kontrol adalah 10 orang laki-laki dan 14 orang perempuan bukan OA lumbal. Dari masing-masing kelompok dilakukan pemeriksaan kadar IL-6 yang nantinya akan dianalisis. Dari hasil penelitian didapatkan rerata umur pada laki-laki kelompok kasus adalah 67,7±10,4 tahun, sedangkan perempuan kelompok kasus adalah 67,7± 6,3 tahun dan rata-rata umur responden pada laki-laki kelompok kontrol adalah 67,7 ± 6,3 tahun sedangkan perempuan kelompok kontrol adalah 64,9± 6,1 tahun.Pada penelitian ini tidak didapatkan perbedaan yang bermakna secara statistik (nilai laki-laki p=0,67, perempuan p=0,123) antara BMI pada kelompok kasus dan kontrol. Dari analisis chi-square menunjukkan tidak ada kemaknaan dalam statistik antara status gizi dengan kejadian OA lumbal. Dari hasil analisis mengenai efek dari kadar interleukin-6 terhadap tejadinya OA lumbal didapatkan simpulan penelitian sebagai berikut: Kadar interleukin-6 tinggi (di atas nilai median 6,60 pg/ml) memiliki kemungkinan 5 kali lebih besar terjadinya OA pada penderita nyeri pinggang bawah (p=0,009). Perempuan dengan kadar interleukin-6 yang tinggi memiliki risiko 6,9 kali lebih besar dibanding laki-laki untuk terjadinya OA lumbal (p=0,03). Kata Kunci : Nyeri Pinggang bawah, OA lumbal, Interleukin-6
ABSTRACT
HIGH INTERLEUKIN-6 AS A MARKER OF LUMBAR OSTEOARTHRITIS IN LOW BACK PAIN PATIENT MORE THAN 55 YEARS OLD
Low Back Pain is a problem for every physician nowadays. The cause and risk factor is still unclear until this day. There still many studies about low back pain causes and risk factors that can usefull for the future treatment. Cytokine has a important role in cartilage degeneration. Which one of them is Interleukin-6 (IL6). But the role of IL-6 at OA is still debating.The purpose of this study is to find out the probability between higher interleukin-6 (IL-6) value with lumbar Osteoarthritis in 55 years old above with complained low back pain. Case control study was the research method used. The samples are man and woman which more than 55 years old with low back pain.The numbers of sample were counted 24 sample for each group. As case is 10 man and 14 woman with Lumbar osteoarthritis, and control is 10 man and 14 woman without Lumbar osteoarthritis. From each samples perfomed interleukin-6 analysis. From the study, the mean of age in case group is 67,7±10,4 years for man, and 67,7± 6,3 tahun for woman. In control group is 67,7 ± 6,3 years for man and 64,9± 6,1 years for woman. In this study, there was no statistically significant (man p=0,67, woman p=0,123) for Body Mass Index between case and control group. From chi-square analysis shown no statistically significant differences between nutritional status and Lumbar Osteoarthritis. Based on Chi-square analysis for the value of interleukin-6, in group that no differ the gender shown significant result (OR=5,00, 95% CI=1,448-17,271, p=0,009). This result shown that the higher interleukin-6 or above the median (6,60 pg/mL) has higher probability for Lumbar osteoarthritis both in man and woman with low back pain.The analysis is shown signficant result also when the analysis differ the gender (OR=6,99. 95% CI=0,040-0,515, p=0,03). The conclusion of this study are : Higher interleukin-6 (above 6,60 pg/ml) has possibility 5 times higher for lumbar Osteoarthritis in patient with low back pain (p=0,009). Woman with high interleukin-6 has a possibility 6,9 times higher than man for lumbar osteoarthritis (p=0,03). Key words : Low Back Pain, Lumbar Osteoarthritis, Interleukin-6
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DAFTAR ISI Sampul Dalam .........................................................................................................
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Abstrak ....................................................................................................................
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Daftar Isi..................................................................................................................
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Daftar Gambar .........................................................................................................
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Daftar Tabel.............................................................................................................
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Daftar Singkatan ......................................................................................................
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Daftar Lampiran.......................................................................................................
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BAB I Pendahuluan .................................................................................................
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1.1 Latar Belakang Masalah .....................................................................................
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1.2 Rumusan Masalah ..............................................................................................
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1.3 Tujuan Penelitian ...............................................................................................
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1.3.1 Tujuan Umum .............................................................................................
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1.3.2 Tujuan Khusus ............................................................................................
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1.4 Manfaat Penelitian .............................................................................................
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1.4.1 Manfaat Teoritis ..........................................................................................
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1.4.2 Manfaat Klinis.............................................................................................
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BAB II Tinjauan Pustaka .........................................................................................
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2.1 Nyeri Pinggang Bawah atau Low Back Pain.......................................................
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2.2 Sendi Facet Lumbal ...........................................................................................
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2.2.1 Anatomi Sendi Facet Lumbal ..................................................................
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2.2.2 Prinsip Biomekanik .................................................................................
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2.2.3 Nyeri yang Dimediasi Proses Inflamasi ...................................................
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2.2.4 Patogenesis Kaskade Inflamasi ................................................................
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2.2.5 Respon terhadap Kaskade Inflamasi ........................................................
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2.3 Osteoarthritis (OA) Lumbal................................................................................
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2.3.1 Karakteristik OA ......................................................................................
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2.3.2 Patofisiologi OA Lumbal..........................................................................
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2.3.3 Imaging pada OA Lumbal ........................................................................
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2.4. Hubungan antara Osteoarthritis, Usia dan Jenis Kelamin ...................................
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2.5 Osteoarthritis dan Interleukin-6 .........................................................................
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2.5.1 Interleukin-6 .............................................................................................
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2.5.2 Hubungan antara Interleukin-6 dan OA ....................................................
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BAB III Kerangka Berpikir, Konsep dan Hipotesis Penelitian ..................................
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3.1 Kerangka Berpikir ..............................................................................................
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3.2 Kerangka Konsep ...............................................................................................
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3.3 Hipotesis Penelitian............................................................................................
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BAB IV Metode Penelitian ......................................................................................
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4.1 Rancangan Penelitian .........................................................................................
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4.2 Lokasi dan Waktu Penelitian ..............................................................................
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4.3 Populasi dan Sampel Penelitian ..........................................................................
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4.3.1 Populasi Penelitian ...................................................................................
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4.3.2 Sampel Penelitian .....................................................................................
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4.3.2.1 Kriteria Inklusi dan Eksklusi Penelitian ...............................................
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4.3.2.2 Cara Pemilihan Sampel dan Besar Sampel ...........................................
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4.4 Variabel Penelitian .............................................................................................
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4.4.1 Klasifikasi dan Identifikasi Variabel .........................................................
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4.4.2 Definisi Operasional Variabel...................................................................
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4.5 Instrumen Penelitian...........................................................................................
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4.6 Prosedur Penelitian ...........................................................................................
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4.7 Alur Penelitian ...................................................................................................
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4.8 Analisis Data......................................................................................................
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BAB V Hasil Penelitian ...........................................................................................
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5.1 Analisis Sampel .................................................................................................
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5.2 Analisis Deskriptif .............................................................................................
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5.2.1 Data Demografis Sampel Penelitian..........................................................
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5.2.2 Data Deskriptif Masing-masing Variabel Penelitian .................................
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5.3 Analisis Inferensial ............................................................................................
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5.3.1 Uji Normalitas ..........................................................................................
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5.3.2 Uji Komparatif .........................................................................................
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5.3.2.1 Uji Independent t-test .........................................................................
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5.3.2.2 Uji Chi Square ....................................................................................
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BAB VI Pembahasan Hasil Penelitian......................................................................
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6.1 Normalitas Data .................................................................................................
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6.2 Analisis Karakteristik Sampel Berdasarkan Umur ..............................................
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6.3 Analisis Karakteristik Sampel Berdasarkan BMI dan Status Gizi .......................
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6.4 Analisis Karakteristik Sampel Berdasarkan Lamanya Keluhan LBP ...................
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6.5 Analisis Kadar Interleukin-6 pada Kasus dan Kontrol ........................................
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6.6 Kelemahan Penelitian.........................................................................................
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BAB VII Simpulan dan Saran ..................................................................................
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7.1 Simpulan Penelitian ...........................................................................................
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7.2 Saran..................................................................................................................
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Daftar Pustaka .........................................................................................................
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Lampiran .................................................................................................................
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DAFTAR GAMBAR
Gambar 2.1 Gambar Sendi facet Lumbal..................................................................
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Gambar 2.2 Gambaran foto polos oblik tulang belakang lumbal...............................
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Gambar 3.1 Kerangka Berpikir ...............................................................................
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Gambar 3.2 Kerangka Konsep Penelitian ................................................................
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Gambar 4.1 Skema Studi Kasus Kontrol .................................................................
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Gambar 4.2 Alur Penelitian .....................................................................................
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Gambar 5.1 Rerata umur sampel penelitian berdasarkan kelompok kasus dan kontrol.................................................................................................
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Gambar 5.2 Perbandingan rerata BMI berdasarkan kelompok kasus dan kontrol ......
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Gambar 5.3 Grafik status gizi sampel penelitian berdasarkan kelompok kasus dan kontrol.................................................................................................
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Gambar 5.4 Grafik perbandingan lamanya keluhan LBP pada kelompok kasus dan kontrol.................................................................................................
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Gambar 5.5 Grafik perbandingan rerata kadar IL-6 pada kelompok kasus dan kontrol.................................................................................................
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Gambar 5.6 Grafik jumlah kadar IL-6 berdasarkan nilai median pada kelompok laki-laki kasus dan kontrol ...................................................................
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Gambar 5.7 Grafik jumlah kadar IL-6 berdasarkan nilai median pada kelompok perempuan kasus dan kontrol...............................................................
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DAFTAR TABEL Tabel 2.1 Molekul Inflamasi yang Terlibat dalam Degenerasi diskus .......................
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Tabel 2.2 Protein Katabolik yang Terlibat dalam Degenerasi Diskus ........................
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Tabel 5.1 Data demografis sampel berdasarkan kasus dan control ............................
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Tabel 5.2 Ringkasan rerata variabel penelitian berdasarkan kelompok kasus dan kontrol .....................................................................................................
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Tabel 5.3 Uji normalitas data variabel-variabel penelitian ........................................
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Tabel 5.4 Hasil uji komparabilitas variabel penelitian untuk kelompok kasus dan kontrol .....................................................................................................
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Tabel 5.5 Hasil analisis chi-square status gizi berdasarkan kelompok kasus dan kontrol .....................................................................................................
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Tabel 5.6 berdasarkan kelompok kasus dan control tanpa membedakan jenis kelamin ....................................................................................................
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Tabel 5.7 Hasil analisis chi-square kadar IL-6 berdasarkan kelompok kasus dan control .....................................................................................................
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DAFTAR SINGKATAN
ADAMTs
: A Disintegrin Like and Metalloprotease with Trombospondin
AP
: Antero-Posterior
BMI
: Body Mass Index
CT-Scan
: Computed Tomography Scan
CI
: Confidence Interval
DD
: Disk Degeneration
IL-1
: Interleukin 1
IL-1β
: Interleukin 1β
IL-6
: Interleukin-6
IMT
: Indeks Massa Tubuh
IVD
: Inter Vertebrae Disk
LBP
: Low Back Pain
M-CSF
: Macrophage colony-stimulating factor
MMP
: Matrix metalloproteinase
MRI
: Magnetic Resonance Imaging
OA
: Osteoarthritis
RANK-L
: Receptor Activator of Nuclear Factor κ B Ligand
TGFα
: Transforming Growth Factor α
TNFα
: Tumor necrosis factor α
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DAFTAR LAMPIRAN Lampiran 1. Ethical Clearance Penelitian .................................................................
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Lampiran 2. Surat Ijin Penelitian ..............................................................................
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Lampiran 3. Tabulasi Data Sampel...........................................................................
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Lampiran 4. Informed Consent Penelitian ................................................................
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Lampiran 5. Pengantar Pemeriksaan Radiologi ........................................................
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Lampiran 6. Kuesioner Penelitian ............................................................................
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Lampiran 7. Hasil Kadar IL-6 ..................................................................................
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Lampiran 8. Analisis statistik SPSS .........................................................................
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