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Abstrak :
ABSTRAK
Pendahuluan. Kesulitan dalam tatalaksana defek tulang yang luas merupakan salah satu tantangan dewasa ini. Selain tatalaksananya yang kompleks juga dapat memberikan dampak jangka panjang negatif yang berat. Penggunaan BMP-2 dalam tatalaksana fraktur dengan defek tulang yang luas memegang peranan penting. BMP-2 berperan pada proses osteogenesis dan chondrogenesis dan menghambat osteoclastogenesis melalui RANKL signaling. Penelitian ini bertujuan untuk mengetahui efek dari perbedaan dosis BMP-2 terhadap penyembuhan fraktur dengan defek tulang yang luas. Metode. Penelitian dilakukan di Laboratorium Animal Gizi di FKUI dan Laboratorium Patologi Anatomi FKUI-RSCM, pada bulan Juli hingga September 2015. Desain penelitian adalah randomized post test control group. Sejumlah 25 ekor tikus putih Sprague Dawley dengan usia 3-4 bulan dan berat badan antara 250 ? 350 gram, dibagi secara acak menjadi kelompok kontrol hidroksiapatit (HA) saja dan kelompok kombinasi HA + BMP-2 1 μg/ml, HA + BMP-2 5 μg/ml, HA + BMP-2 10 μg/ml, HA + BMP-2 20 µg/ml. Tiap kelompok dilakukan tindakan berupa frakturisasi dengan defek tulang 10mm pada femur kanan dan dilakukan fiksasi interna dengan menggunakan intramedullary k-wire ukuran 1,4 mm secara retrograd. Setelah 6 minggu dilakukan penilaian secara histomorfometri, radiologis dan Scanning Electron Microscope (SEM). Hasil. Berdasarkan hasil penelitian secara histomorfometri ditemukan terdapat perbedaan rerata total area kalus yang bermakna diantara kelompok penelitian (p<0,001),terdapat perbedaan bermakna rerata area penulangan antara kelompok kontrol dengan kelompok 1 μg/ml, 5 μg/ml, 10 μg/ml, 20 μg/ml (masing-masing p=0,009, p=0,016, p=0,009 dan p=0,016), terdapat perbedaan bermakna rerata area kartilago antara kelompok kontrol dengan kelompok 1 μg/ml, 5 μg/ml, 10 μg/ml, 20 μg/ml (masing-masing p=0,009, p=0,009, p=0,009 dan p=0,028), terdapat perbedaan bermakna rerata area fibrosis antara kelompok kontrol dengan kelompok 1 μg/ml dengan kelompok kontrol dan 10 μg/ml(masing-masing p=0,047 dan p=0,009).Secara radiologis dengan RUST score didapatkan perbedaan bermakna antara kelompok kontrol dengan kelompok 1 μg/ml, 5 μg/ml, 10 μg/ml, 20 μg/ml (masing-masing p=0,005, p=0,006, p=0,005 dan p=0,006). Dengan SEM didapatkan gambaran kalus yang lebih homogen dan padat pada kelompok 10μg/ml dibandingkan dengan 5 μg/ml dan 20 μg/ml. Kesimpulan: Pemberian BMP-2 dapat menstimulasi proses penyembuhan fraktur pada defek tulang luas (critical bone defect) yang bermakna secara statistik, histomorfometri, radiologis maupun secara kualitatif dengan SEM. Terdapat dosis optimal dalam pemberian BMP-2.ABSTRACT
Introduction: Difficulties in the management of extensive bone defects is one of today's challenges. It is not only complex treatment but also can provide long-term negative severe effects. The use of BMP-2 in the treatment of fractures with extensive bone defect plays an important role. BMP-2 plays a role in the process of osteogenesis and chondrogenesis and inhibits osteoclastogenesis via the RANKL signaling. This study aims to determine the effect of differences in doses of BMP-2 on the healing of the fracture with extensive bone defects. Methods: The study was conducted at the Laboratory of Animal Nutrition at the Faculty of Medicine University of Indonesia (FMUI) in July until September 2015. The study design was randomized posttest control group. A number of 25 Sprague Dawley rats aged 3-4 months and bodyweight between 250-350 grams, were randomly divided into a control group of hydroxyapatite (HA) alone and HA+BMP-2 1 µg / ml, HA+BMP -2 5 ug / ml, HA + BMP-2 10 µg / ml, HA + BMP-2 20 ug / ml. Each group carried out fracturization with 10mm bone defect in right femur and internal fixation by using intramedullary K-wire size of 1.4 mm retrograde. After 6 weeks we did histomorfometri assessment, radiological and Scanning Electron Microscope (SEM). Results: Based on the research results histomorfometrcally found there are differences in the mean total area of ​​callus significantly between the study group (p <0.001), there were significant differences in the mean area of ​​woven bone between the control group with group 1 ug / ml, 5 µg / ml, 10 µg / ml, 20 ug / ml (respectively p = 0.009, p = 0.016, p = 0.009 and p = 0.016), there were significant differences in the average area of ​​the cartilage between the control group with group 1 ug / ml, 5 µg / ml, 10 µg / ml, 20 ug / ml (respectively p = 0.009, p = 0.009, p = 0.009 and p = 0.028), there were significant differences in the average area of ​​fibrosis between the control group with group 1 ug / ml in the control group and 10 mg / ml (respectively -masing p = 0.047 and p = 0.009) .In radiologist assessment with RUST scores obtained significant differences between the control group and group 1 ug / ml, 5 µg / ml, 10 µg / ml, 20 µg / ml (respectively p = 0.005 , p = 0.006, p = 0.005 and p = 0.006). SEM features with callus more homogeneous and dense in the group of 10μg / mL compared with 5 ug / ml and 20 µg / ml. Conclusion: Administration of BMP-2 could stimulate the process of fracture healing in large bone defects (critical bone defect) which was statistically significant with histomorfometri assestment, radiological and qualitatively with the SEM. There is an optimal dose in the administration of BMP-2.;Introduction: Difficulties in the management of extensive bone defects is one of today's challenges. It is not only complex treatment but also can provide long-term negative severe effects. The use of BMP-2 in the treatment of fractures with extensive bone defect plays an important role. BMP-2 plays a role in the process of osteogenesis and chondrogenesis and inhibits osteoclastogenesis via the RANKL signaling. This study aims to determine the effect of differences in doses of BMP-2 on the healing of the fracture with extensive bone defects. Methods: The study was conducted at the Laboratory of Animal Nutrition at the Faculty of Medicine University of Indonesia (FMUI) in July until September 2015. The study design was randomized posttest control group. A number of 25 Sprague Dawley rats aged 3-4 months and bodyweight between 250-350 grams, were randomly divided into a control group of hydroxyapatite (HA) alone and HA+BMP-2 1 µg / ml, HA+BMP -2 5 ug / ml, HA + BMP-2 10 µg / ml, HA + BMP-2 20 ug / ml. Each group carried out fracturization with 10mm bone defect in right femur and internal fixation by using intramedullary K-wire size of 1.4 mm retrograde. After 6 weeks we did histomorfometri assessment, radiological and Scanning Electron Microscope (SEM). Results: Based on the research results histomorfometrcally found there are differences in the mean total area of ​​callus significantly between the study group (p <0.001), there were significant differences in the mean area of ​​woven bone between the control group with group 1 ug / ml, 5 µg / ml, 10 µg / ml, 20 ug / ml (respectively p = 0.009, p = 0.016, p = 0.009 and p = 0.016), there were significant differences in the average area of ​​the cartilage between the control group with group 1 ug / ml, 5 µg / ml, 10 µg / ml, 20 ug / ml (respectively p = 0.009, p = 0.009, p = 0.009 and p = 0.028), there were significant differences in the average area of ​​fibrosis between the control group with group 1 ug / ml in the control group and 10 mg / ml (respectively -masing p = 0.047 and p = 0.009) .In radiologist assessment with RUST scores obtained significant differences between the control group and group 1 ug / ml, 5 µg / ml, 10 µg / ml, 20 µg / ml (respectively p = 0.005 , p = 0.006, p = 0.005 and p = 0.006). SEM features with callus more homogeneous and dense in the group of 10μg / mL compared with 5 ug / ml and 20 µg / ml. Conclusion: Administration of BMP-2 could stimulate the process of fracture healing in large bone defects (critical bone defect) which was statistically significant with histomorfometri assestment, radiological and qualitatively with the SEM. There is an optimal dose in the administration of BMP-2.

Abstrak :
[ABSTRAK
Pendahuluan. Irigasi dan debridement yang adekuat dinilai sebagai faktor yang paling menentukan dalam pencegahan infeksi pada fraktur terbuka. Povidone Iodine dan hidrogen peroksida sering digunakan sebagai adjuvant pada proses irigasi untuk membunuh mikroorganisme dan menurunkan angka infeksi. Penelitian ini bertujuan untuk menilai pengaruh povidone iodine dan hidrogen peroksida terhadap penyembuhan fraktur dan reaksi jaringan yang terjadi. Metode. Empat puluh ekor tikus Sprague Dawley jantan dialokasikan acak ke dalam kelompok perlakuan, yaitu; kelompok I (kontrol), kelompok II (povidone iodine 10%), kelompok III (povidone iodine 1%), dan kelompok IV (hidrogen peroksida 3%). Pada minggu pertama, kedua, dan kelima masing-masing dikorbankan 3 ekor tikus pada setiap kelompok. Evaluasi penyembuhan fraktur dilakukan dengan histomorfometri menggunakan program ImageJ®, variabel yang dinilai meliputi; persentase jaringan fibrosa, jaringan tulang rawan, dan jaringan penulangan pada kalus. Reaksi jaringan dinilai dari jumlah sel limfosit dan makrofag yang dinilai secara semikuantitatif. Analisis statistik dilakukan dengan uji ANCOVA dilanjutkan dengan uji post hoc Dunnett. Hasil. Persentase luas jaringan penulangan terbanyak ditemukan pada kelompok III, diikuti oleh kelompok I, kelompok IV, dan kelompok II. Persentase luas jaringan fibrosa terbanyak ditemukan pada kelompok II, diikuti oleh kelompok IV, kelompok I, dan kelompok III. Reaksi jaringan terbesar ditemukan pada kelompok II, diikuti oleh kelompok IV, kelompok III, dan kelompok I. Pada uji ANCOVA ditemukan perbedaan antar kelompok yang bermakna. Pada uji Dunnett terdapat perbedaan yang bermakna antara kelompok II dan IV terhadap kontrol. Simpulan. Povidone iodine 1% menunjukkan gangguan penyembuhan fraktur dan reaksi jaringan yang minimal.

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ABSTRACT
Introduction. Adequate irrigation and debridement are important factors to prevent infection in open fractures. Povidone iodine and hydrogen peroxide are adjuvants often used in irrigation to kill microorganisms and prevent infections. This study aims to determine the effect of povidone iodine and hydrogen peroxide on fracture healing and also reaction of host tissue to their presence. Methods. Fourty male Sprague Dawley rats were allocated randomly into group I (control), group II (10% povidone iodine), group III (1% povidone iodine), and group IV (3% hydrogen peroxide). Three rats on each group were sacrificed on the first, second, and fifth week. Evaluation of fracture healing was done by histomorphometry using ImageJ®, variables measured were; percentage of fibrous tissue, cartilage tissue, and osseous tissue in fracture callus. Reaction of host tissue was analyzed by semiquantative evaluation of lymphocytes and macrophages. Statistical analysis was performed with ANCOVA test followed by Dunnett post hoc test. Results. The highest percentage of osseous tissue was found in group III, followed by Group I, Group IV and Group II. The highest percentage of fibrous tissue was found in group II, followed by group IV, group I, and group III. The largest tissue reaction was found in group II, followed by group IV, group III, and group I. In ANCOVA test, there was significant difference found between groups. In Dunnett test, significant differences were found between group II and IV to control. Conclusion. One percent povidone iodine caused minimal impairment of fracture healing and host tissue reaction., Introduction. Adequate irrigation and debridement are important factors to prevent infection in open fractures. Povidone iodine and hydrogen peroxide are adjuvants often used in irrigation to kill microorganisms and prevent infections. This study aims to determine the effect of povidone iodine and hydrogen peroxide on fracture healing and also reaction of host tissue to their presence. Methods. Fourty male Sprague Dawley rats were allocated randomly into group I (control), group II (10% povidone iodine), group III (1% povidone iodine), and group IV (3% hydrogen peroxide). Three rats on each group were sacrificed on the first, second, and fifth week. Evaluation of fracture healing was done by histomorphometry using ImageJ®, variables measured were; percentage of fibrous tissue, cartilage tissue, and osseous tissue in fracture callus. Reaction of host tissue was analyzed by semiquantative evaluation of lymphocytes and macrophages. Statistical analysis was performed with ANCOVA test followed by Dunnett post hoc test. Results. The highest percentage of osseous tissue was found in group III, followed by Group I, Group IV and Group II. The highest percentage of fibrous tissue was found in group II, followed by group IV, group I, and group III. The largest tissue reaction was found in group II, followed by group IV, group III, and group I. In ANCOVA test, there was significant difference found between groups. In Dunnett test, significant differences were found between group II and IV to control. Conclusion. One percent povidone iodine caused minimal impairment of fracture healing and host tissue reaction.]

Abstrak :
Pendahuluan: Penanganan nonunion dan delayed union bukanlah penanganan yang murah dan mudah. Berbagai metode telah dilakukan untuk mengatasi masalah tersebut. Beras angkak terbukti memiliki peranan dalam penyembuhan fraktur. Beras angkak, mengandung monakolin, suatu senyawa dengan aktivitas sebanding lovastatin. Pemberian statin secara lokal dan oral terbukti meningkatkan penyembuhan tulang dengan menginduksi diferensiasi osteoblas melalui peningkatan ekspresi BMP-2. Penelitian ini dilakukan untuk membuktikan efektivitas monakolin pada beras angkak dalam meningkatkan ekspresi BMP-2 dan penyembuhan fraktur pada model delayed union tikus sprague- dawley. Material dan Metode: Studi eksperimental pada 24 hewan coba tikus putih Sprague-Dawley (SD) yang telah mengalami patah tulang femur disertasi dengan gangguan vaskularisasi (model delayed-union). Hewan coba dibagi menjadi empat kelompok (n=6) terdiri dari; kelompok pemberian ekstrak monakolin selama empat minggu (PM4), kelompok pemberian ekstrak monakolin selama dua minggu (PM2), kelompok kontrol empat minggu (KM4) dan kelompok kontrol dua minggu (KM2). Setelah dilakukan sacrifice pada minggu kedua dan keempat, dilakukan penilaian ekspresi BMP-2 secara semikuantitatif dengan pewarnaan imunohistokimia melalui skor imunoreaktif (IRS). Analisis histomorfometri untuk menilai penyembuhan fraktur dengan mengukur persentase area fibrosa, tulang rawan dan tulang imatur. Hasil: Pada evaluasi parameter IRS dan histomorfometri didapatkan ekspresi BMP-2 lebih tinggi (p=0.03), persentase area fibrosa lebih sedikit (p=0.005) dan area tulang rawan lebih besar (p=0.04) pada kelompok PM2 dibandingkan dengan kelompok KM2. Selain itu didapatkan pula secara ekspresi BMP-2 lebih tinggi (p=0.011), presentase area tulang imatur lebih besar (p=0.01), dan presentase area fibrosa lebih kecil (p=0.03) pada kelompok PM4 dibandingkan dengan kelompok KM4. Di sisi lain, didapatkan presentase area fibrosa lebih kecil (p=0.02), area tulang rawan lebih sedikit (p=0.05), dan peningkatan area tulang imatur lebih besar (p=0.04) pada kelompok PM4 dibandingkan dengan kelompok PM2. Ekspresi BMP-2 sama-sama meningkat pada kelompok PM2 dan PM4. Kesimpulan: Pemberian monakolin pada beras angkak pada model delayed-union tikus Sprague Dawley terbukti meningkatkan ekspresi BMP-2 dan meningkatkan penyembuhan fraktur. ......Introduction: Management of nonunion and delayed union could be difficult and expensive. Various methods have been studied to overcome this problem. Red-yeast-rice has a role in fracture healing. Red-yeast-rice contains monacolin, which has similar activity to lovastatin. Local application and oral administration of statins have been shown to improve bone healing by inducing osteoblast differentiation and matrix production via increasing BMP-2 expression. This study was conducted to prove the effectiveness of monacolins inside red-yeast-rice in increasing the expression of BMP-2 and fracture healing. Methods: This experimental animal study was conducted using 24 delayed union models Sprague-Dawley (SD) Rats. There were 4 groups (n=6), consist of; 4-weeks-given-monacolin group (PM4), 2-weeks-given-monacolin group (PM2), 4-weeks-control group (PM2) and 2-weeks control group (KM2). After they were sacrificed in the second and fourth weeks, immunohistochemical staining was conducted to evaluate BMP-2 expression by Immunoreactive Score (IRS). The histomorphometric evaluation was also conducted to evaluate fracture healing by measuring fibrous area, cartilage area, and woven bone area percentage. Results: There was significantly higher BMP-2 expression (p=0.03), less fibrous area (p=0.05), and larger cartilage area (p= 0.04) in the PM2 group compared to the KM2 group. There was significantly higher expression of BMP-2 (p=0.011), larger woven bone area (p=0.01), and less fibrous area (p = 0.03) in the PM4 group compared to the KM4 group. It was also presented, there was a significantly less fibrous area (p=0,02), larger cartilage area (p=0.05), and larger woven bone area (p=0.04) in the PM4 group compared to the PM2 group. The expression of BMP-2 in the PM2 group was as high as the PM4 group. Conclusion: Monacolin in red-yeast-rice effectively increased BMP-2 expression and fracture healing in the delayed union model of SD rats.