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"PendahuluanFraktur kominutif dapat memberikan permasalahan berupa nonunion. Penggunaan graft untuk mengatasi masalah tersebut masih diperdebatkan. Autograft merupakan baku emas dalam penggunaan graft, namun keterbatasannya adalah persediaan yang terbatas. Untuk itu banyak beredar pengganti autograft seperti allograft, xenograft, dan graft sintetik (biomaterial scaffold). Graft harus mempunyai biokompatibilitas yang baik guna mendukung penyembuhan fraktur.MetodeDilakukan randomized post test only control group terhadap 30 tikus Sprague Dawley guna menilai biokompatibilitas scaffold secara in vivo. Scaffold yang digunakan adalah hidroksiapatit (HA)-Bongros®, nanokristalin HA-CaSO4 (Perossal®), nanokristalin HA (Ostim®), morselized bovine xenograft (BATAN), dan HA-lokal bank jaringan dr. Sutomo. Dilakukan penilaian reaksi jaringan (jumlah sel datia benda asing dan limfosit), skor radiologis dan histologis pada minggu ke-8.HasilPerbedaan bermakna ditunjukkan pada jumlah sel datia benda asing memberikan perbedaan bermakna (p=0,003), namun tidak dengan limfosit (p=0,397). Scaffold HA-lokal menunjukkan jumlah sela datia benda asing paling banyak. Skor histologis memberikan perbedaan bermakna (p=0,013) , namun skor radiologis tidak menunjukkan perbedaan bermakna (p = 0,204 untuk proyeksi antero-posterior dan p = 0,506 untuk proyeksi mediolateral). Didapatkan 2 subjek yang drop out yaitu 1 subjek pada kelompok kontrol (implant failure) dan 1 subjek pada kelompok IV (osteomielitis). Terdapat korelasi yang bermakna antara jumlah sel datia benda asing dan skor histologis (p=0,034).DiskusiBiokompatibilitas scaffold secara in vivo ditentukan oleh komponen fisik dan kimia pembentuknya. Secara fisik, scaffold yang memiliki pori-pori menunjukkan skor histologis yang lebih baik. Komponen kimia pembentuk scaffold dapat memengaruhi reaksi jaringan. Jumlah sel datia benda asing berhubungan dengan sitotoksisitas scaffold.

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Introduction

Comminuted fracture may result as nonunion. The use of bone graft is still debatable for treating comminuted fracture. Autograft is the gold standard of bone graft. However, it has a limitation in supply. Therefore, the use of other source of graft (allograft, xenograft, or synthetic) is increasing. Graft must have good biocompatibility in order to enhance fracture healing.

Method

Randomized post test only control group was conducted in 30 Sprague-Dawley rat in order to evaluate biocompatibility of the scaffold. We used hidroxyapatite (HA)-Bongros®, nanocrystalline (HA)-CaSO4 (Perossal®), nanocrystalline HA (Ostim®), morselized bovine xenograft (BATAN), dan local HA from dr. Sutomo Hospital as the scaffold. Tissue reaction (the amount of foreign body giant cell and lymphocyte), radiological and histological score was evaluated at 8th weeks.

Result

The amount of foreign body giant cell (FBGC) and histological score showed significant difference (p=0,003 and p=0,013). Local HA scaffold showed the most FBGC accumulation. There was no significant difference in the amount of lymphocyte (p=0,397) and radiological score (p=0,204 for antero-posterior projection and p=0,506 for medio-lateral projection). Two subjects were considered drop out, one due to implant failure (control group) and the other due to osteomyelitis (group IV). There was significant correlation between the amount of foreign body giant cell and histological score (p=0,034).

Discussion

Both physical and chemical factor influenced biocompatibility of scaffold. Scaffolds that have pores showed better histological score compared to that has none. Chemical compound of the scaffold play important role in tissue reaction. The amount of FBGC showed the cytotoxic level of the scaffold.

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"Latar belakang : Delayed union merupakan salah satu komplikasi penyembuhan fraktur dengan insiden berkisar antara 4,4% hingga 31%. Penatalaksanaan delayed union dapat menimbulkan masalah ekonomi dan kesehatan pada pasien. Angiogenesis memiliki peran penting dalam penyembuhan fraktur. Sildenafil telah terbukti menjadi stimulator poten angiogenesis melalui peningkatan regulasi faktor pro-angiogenik atau yang dikenal sebagai vascular endothelial growth factor (VEGF). Studi ini akan menentukan apakah sildenafil juga mempengaruhi aktivitas angiogenesis dengan ekspresi VEGF dan mempercepat penyembuhan fraktur dengan delayed union.Metode : Penelitian ini merupakan penelitian eksperimental dengan post test only control group design, yang dilakukan pada model delayed union tikus Sprague dawley menggunakan analisis histomorfometri dan imunohistokimia. Penelitian ini diawali dengan studi pendahuluan untuk menentukan model delayed union yang hasilnya akan digunakan sebagai kontrol pada penelitian selanjutnya. Tikus dibagi secara acak menjadi empat kelompok : kelompok delayed union (n=6), kelompok dengan pemberian sildenafil 3,5 mg/kgbb (n=6), sildenafil 5 mg/kgbb (n=6) dan sildenafil 7,5 mg/kgbb (n=6). Parameter yang dievaluasi meliputi luas total kalus, area tulang rawan, area penulangan, jaringan fibrosa dan ekspresi VEGF. Pengukuran dilakukan pada minggu ke-2 dan ke-4 setelah intervensi.Hasil : Setelah dua minggu kondisi delayed union, sildenafil secara signifikan meningkatkan parameter penyembuhan fraktur. Terjadi peningkatan yang signifikan pada total luas kalus (p=0,004), area tulang rawan (p=0,015), area penulangan (p=0,001), jaringan fibrosa (p=0,005) dan ekspresi VEGF (p=0,037). Setelah empat minggu, perbedaan yang signifikan hanya terjadi pada area penulangan (p=0,015) dan jaringan fibrosa (p=0,001).Diskusi : Analisis histomorfometri dan imunohistokimia menunjukkan peningkatan yang signifikan pada parameter penyembuhan fraktur dan ekspresi VEGF. Hal ini menunjukkan terjadinya percepatan penyembuhan fraktur dan peningkatan pembentukan pembuluh darah. Semakin sedikitnya area kalus dan berkurangnya area tulang rawan serta meningkatnya area penulangan menunjukkan percepatan proses penyembuhan fraktur. Sildenafil meningkatkan aktivitas angiogenesis dengan meningkatnya ekspresi VEGF dan perbaikan vaskularisasi. Perbaikan vaskularisasi pada fraktur tidak hanya memperbaiki oksigenasi dan nutrisi jaringan, tetapi juga menyediakan suplai mesenchymal stem cells (MSCs) pada jaringan fraktur.Simpulan : Sildenafil terbukti mempercepat penyembuhan fraktur dan meningkatkan ekspresi VEGF pada fraktur dengan delayed union.

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Introduction : Inspite of various methods of management to achieve optimum fracture healing, delayed union remains a major problem. The incidence of delayed union ranging from 4.4% to 31%. The management of such problem include secondary operative intervention, which results in economic impact and patient morbidity. Angiogenesis plays an important role in fracture healing. Sildenafil has been shown to be a potent stimulator of angiogenesis through upregulation of pro-angiogenic factors or known as vascular endothelial growth factor (VEGF). This study will evaluate whether sildenafil also influences VEGF expression and bone formation during the process of healing in delayed union fracture.

Method : This study was an experimental study with post test only control group design. It was performed ina delayed union femur fracture model of Sprague Dawley rats using histomorphometric and immunohistochemistry evaluation. A pilot study was initiated previously to determine the model for delayed union fracture healing, and the results were used as the control. Rats were randomized into four groups : delayed union (n=6), administration of sildenafil 3.5 mg/kgbw (n=6), sildenafil 5 mg/kgbw (n=6) and sildenafil 7.5 mg/kgbw (n=6). The parameters evaluated include total area of callus, cartilage area, total osseous tissue, fibrous tissue and VEGF expression. The measurement was carried out at 2 and 4 weeks after intervention.

Results : After two weeks of delayed union fracture healing, sildenafil significantly increased the parameter of fracture healing. The results showed a significant increase of total area of callus (p=0.004), cartilage area (p=0.015), total osseous tissue (p=0.001), fibrous tissue (p=0.005) and VEGF expression (p=0.037). After four weeks, the results were still significant in total osseous tissue (p=0.015) and fibrous tissue (p=0.001).

Discussion : Histomorphometric and immunohistochemistry analysis showed a significant increase of fracture healing parameter and higher expression of the proangiogenic factors (VEGF). Such result confirmed the increase of bone and vascular formation. A smaller callus area with a slightly reduced amount of cartilaginous tissue and increased osseous tissue indicated an accelerated healing process. Sildenafil improves the expression of VEGF and vascularization repair. The vascular invasion in a fracture not only provide oxygen and nutrients needed to repair the injured tissue cells, but also provide an additional source of MSCs.

Conclusion : Sildenafil is proven to effectively accelerate fracture healing and increase VEGF expression in delayed union fracture."

"Penyembuhan fraktur masih merupakan masalah besar. Banyak hal dilakukanuntuk mempercepat penyembuhan fraktur dan menghindari komplikasipenyembuhan fraktur. Pemberian vitamin C salah satunya. Penelitian ini bertujuanuntuk mengetahui peran vitamin C dalam mempercepat penyembuhan frakturpada fraktur dengan periosteal stripping di femur tikus putih Spague DawleyEvaluasi percepatan penyembuhan fraktur dilakukan secara radiologis denganskor RUST dan histologis dengan histomorphometri. Penelitian ini adalahpenelitian eksperimental. Penilaian dilakukan terhadap 32 ekor tikus dengandosis vitamin C yang berbeda-beda dan dievaluasi pada minggu ke 2 dan mingguke 4. Terdapat percepatan penyembuhan fraktur pada kelompok dengan dosisbesar pada skor RUST di minggu ke-4. Secara histologis pada histomorphometrididapatkan percepatan penyembuhan fraktur,tetapi secara statistik tidak bermakna.

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Fracture Healing still became a problem. There are many things to do to enhance

and avoid the complication of fracture healing. Vitamin C is one of the way to

enhance the fracture healing.. The purpose of this study is to know the role of

vitamin C in enhancement the fracture healing in fracture with periosteal stripping

at white rats femur. The evaluation of enhancement of fracture healing used

radiograpic with RUST score and histologic with histomorphometry. This is an

experimental study. The study used 32 rats which were given vitamin C in

different dosage and was evaluated at the 2nd and 4th week. There is

enhancement of fracture healing in all dosage, especially the large dosage of

vitamin C in RUST score evaluation in the 4th week. In histomorphometry

evaluation there were enhancement of fracture healing but statistically no

significant"

"[ABSTRAKPendahuluan. 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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ABSTRACTIntroduction. 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. 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."

"Delayed union adalah masalah besar pada penyembuhan fraktur. Bone Morphogenetic Protein (BMP) terbukti dapat mempercepat penyembuhan tulang dari 30 sampai 40 persen. Salah satu obat yang dapat digunakan untuk meningkatkan BMP2 dan BMP4 adalah pentoxyfillin. Pada studi eksperimental ini dilakukan untuk menginvestigasi pengaruh pentoxyfillin oral terhadap percepatan penyembuhan tulang pada fraktur dengan periosteal stripping di femur tikus putih Spague Dawley sejumlah 24 ekor. Evaluasi dilakukan secara radiologis dengan skor RUST dan histologis dengan histomorphometri pada minggu ke 4. Terdapat percepatan penyembuhan fraktur pada skor RSUT maupun pada histomorfometri, namun tidak bermakna secara statistik. Namun didapatkan perbedaan bermakna pada area penulangan dan area tulang rawan pada kelompok dengan dosis obat tertentu. Pentoxyfillin oral berpengaruh pada percepatan penyembuhan fraktur pada delayed union, dengan dosis 100mg/KgBB/hari.

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Delayed union is an important problem during fracture healing process. Bone Morphogenetic Protein (BMP) has shown to accelerate the bone healing from 30 to 40 percent. Pentoxyfilline is a drug used to increase BMP2 and BMP4. This experimental study was conducted to investigate the effect of oral pentoxyfilline accelerating bone healing process on fractured femur with periosteal strapping on 24 Sprague Dawley Rats. The evaluation of RUST score and histologically on histomorphometric analysis was done on the forth week. There was an enhancement of fracture healing in terms of RUST score and histomorphometric analysis, but statistically not significant. However, the significant difference was observed in area of osseous tissue and cartilage area in the dose group. Oral Pentoxyfilline accelerates the fracture healing process in delayed union model, with dosing of 100mg/KgBW/day."

"Pendahuluan: Fraktur merupakan masalah kesehatan utama karena sering terjadi, pengobatan yang kompleks dan mahal, serta hilangnya produktivitas. Masalah diperberat bila terjadi komplikasi berupa delayed union atau nonunions. Dalam menilai pengaruh suatu tindakan intervensi terhadap penyembuhan fraktur, diperlukan suatu model perlambatan penyembuhan fraktur dan suatu metode penilaian yang akurat yang meliputi radiologi, biomekanik, dan histologi. Berbagai model perlambatan peyembuhan fraktur telah di laporkan dengan melakukan stripping periosteal dengan menggunakan cauter yang menghasilkan tidak hanya efek mekanik namun juga efek termal. Selain itu, metode penilaian akurat radiologi, biomekani modern bergantung terhadap instrumen yang belum tersedia secara masal. Penilaian histologi melalui histomorphometri dapat dikerjakan tanpa bergantung pada instrument modern dan mahal. Hal ini ditunjang dengan tersedianya program image J yang merupakan program dari NIH dan dapat diperoleh secara cumacuma. Metode: Penelitian dilakukan pada bulan Juli hingga September 2013 di Departement Patologi Anatomi FKUI. Penilaian dilakukan terhadap 24 ekor tikus dengan fraktur dengan dan tanpa perlakuan mekanis pada periosteum yang kemudian dievaluasi pada minggu ke-2 dan minggu ke-4. Perlakuan mekanis pada periosteum berupa Stripping sirkular dengan bistruri sepanjang 10mm disekitar fraktur. Penilaian histomorfometri dilakukan secara semi-automated dengan bantuan program image-j, meliputi penilaian parameter total area kalus, area penulangan, area tulang rawan dan area jaringan fibrosa. Evaluasi dilakukan dengan membandingkan perubahan pada kelompok 2 minggu, kelompok 4 minggu serta beda kelompok 2 dan 4 minggu. Hasil: Pemeriksaan Histomorfometri minggu ke-2 dan minggu ke-4 didapatkan area penulangan, area tulang rawan dan area jaringan fibrosa kelompok perlakuan lebih kecil dibandingkan pada kelompok kontrol yang secara statistik bermakna. Pada evaluasi beda histomorfometri minggu ke-2 dan minggu ke-4 antara kelompok kontrol dan kelompok perlakuan didapatkan perlambatan proses penyembuhan yang juga secara statistik berbeda bermakna. Kesimpulan: Analisa histomormofetri dengan image-J dapat dilakukan tanpa bergantung pada instrumentasi yang modern dan perlakuan mekanik pada periosteum berupa stripping sejauh 5mm dapat menghambat penyembuhan fraktur.

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Introduction: Fracture is a major health problem because the complexity and expensive treatment, and also loss of productivity that accompanying. That problem worsened if there is complications such as delayed-union or nonunions. Many intervention was done to prevent that complication. In assessing the effect of intervention, a model and also analytic method that includes radiology, biomechanics, and histology were needed. Various models of delayed fracture healing have been reported by stripping the periosteal with cauter which produces not only mechanical but also thermal effect. Moreover, latest radiological and biomechanical assessment rely on instruments that are not available in every places. Histological assessment through histomorphometri can be done without relying on modern and expensive instruments. This evaluation method is supported by the availability of image-J program which is a program of the NIH, and can be obtained free of charge.

Method: The study is an experimental study that was conducted in the Department of Pathology Faculty of Medicine, University of Indonesia, on July to September 2013. 24 rats was divided into 2 group. 1 group was performed mechanical force to bone only to get fracture and other was done by giving mechanical force to bone and also periosteum. Each group was evaluated at 2 weeks and 4 weeks. Histomorfometri assessment was performed semi-automatically with the aid of image-j software. The paramater that measure was total area of callus, newbone area, cartilage area, and fibrotic area. Evaluation is done by comparing the difference of 2 group in 2 weeks, 4 weeks, and also the changes of 2 and 4 weeks of each group.

Result: From Histomorfometric examination on 2nd week and 4th week, we found that newbone formation area, cartilage area and fibrous tissue area of treatment group smaller than in the control group and statistically significant. We also found that there was delaying of healing process in comparring the changing in 2nd to 4th week of treatment group and it is also statistically significant.

Conclusions: Histomormofetri analysis with image-J can be done without relying on modern instrumentation, mechanical force on periosteum on a fracture site by periosteal stripping could inhibit healing fracture especially in histological pattern."

"Latar Belakang Hipertensi dan fraktur merupakan masalah kesehatan yang sering terjadi ACE inhibitor telah dilaporkan dapat mempromosikan diferensiasi osteoblas meningkatkan mineralisasi dan sekresi matriks tulang sehinga konsumsinya diharapkan mampu mempercepat penyembuhan Tujuan Penelitian bertujuan mengetahui efek pemberian ACE inhibitor terhadap proses penyembuhan fraktur model delayed union Metode Enam belas femur tikus yang dibuat sesuai model delayed union dibagi secara acak menjadi kelompok kontrol kelompok perlakuan Captopril dosis 4 mg kgBB kelompok perlakuan Captopril dosis 8 mg kgBB dan kelompok Captopril dosis 16 mg kgBB Evaluasi dilakukan pada minggu ke 4 secara radiologis foto polos dan histomorfometri Hasil Pada histomorfometri minggu ke 4 didapatkan peningkatan area penulangan yang bermakna terhadap kontrol p 0 033 terutama pada pemberian Captopril dosis 8 mg kgBB p 0 008 dan dosis 16 mg kgBB p 0 015 Penurunan area fibrosa yang bermakna terhadap kontrol p 0 042 terjadi pada Captopril dosis 4 mg kgBB p 0 020 dan dosis 8 mg kgBB p 0 012 Secara radiologis didapatkan peningkatan skor RUST semua kelompok perlakuan yang bermakna terhadap kontrol p 0 021 Kesimpulan Pemberian Captopril dapat menstimulasi proses penyembuhan fraktur pada model delayed union secara radiologis dan histomorfometri Captopril dosis 8 mg kgBB menunjukkan efek yang paling signifikan dalam proses penyembuhan fraktur."

"Pendahuluan: Fraktur adalah salah satu penyakit yang menjadi permasalahan yang cukup besar dalam bidang kesehatan di dunia, terutama di negara berkembang. Secara umum fraktur dapat sembuh dengan normal. Pada beberapa kondisi, penyembuhan fraktur mengalami komplikasi seperti delayed union atau non union. Penyembuhan fraktur yang sukses merupakan suatu interaksi yang kompleks antara proses angiogenesis dan osteogenesis. Stimulus fisika berupa pajanan PEMF (pulsed electromagnetic fields) menunjukkan pengaruh proses osteogenesis baik dalam tahap perkembangan penulangan embrio dan tahap penyembuhan fraktur.Tujuan: Penelitian ini bertujuan untuk mengetahui penyembuhan fraktur tulang delayed union pada hewan coba pada pemberian ELF-PEMF dengan melihat skor radiologi RUST dan Failure Load dari Pemberian Gaya Aksial.Metode: Dilakukan uji eksperimental pada 56 hewan coba di Laboratorium Hewan Departemen Gizi, Fakultas Kedokteran Universitas Indonesia, dengan membandingkan nilai RUST Score dan Load Score pada kedua kelompok hewan coba.Hasil: Penelitian dilakukan selama Agustus-September 2018. Tidak ada perbedaan karakteristik hewan coba pada penelitian. Didapati bahwa terdapat perbedaan bermakna Rust Score pada kelompok perlakuan dan kelompok kontrol pada setiap minggu pemeriksaan dan terdapat perbedaan bermakna Load Score pada minggu keempat dan kelima.Kesimpulan: Penelitian ini menyimpulkan terdapat perbaikan penyembuhan fraktur delayed union pasca pemberian ELF-PEMF dilihat dari perbedaan nilai Rust score dan load score.

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Background: Fracture is a major health problem in the world, especially in developing countries. Usually, fractures can heal normally. In some conditions, the healing process becomes delayed union or non union. Successful healing of fractures is a complex interaction between angiogenesis and osteogenesis. Physical stimuli such as exposure of PEMF (pulsed electromagnetic fields) influences the osteogenesis process both in the development stage of embryo reinforcement and the fracture healing stage.Objective: The aim is to determine the healing of delayed union fractures in experimental animals after exposure to ELF-PEMF.Methods: The experimental study was conducted at Department of Nutrition Animal Laboratory, Faculty of Medicine, Universitas Indonesia with 56 experimental rats. The study was conducted by comparing the RUST Score and Load Score values ​​in the two experimental animal groupsResult: The study was conducted during August-September 2018 There was no difference in animal characteristics in the study. There was significant difference in Rust Score in both groups in each examination week and there were significant differences in Load Score in the fourth and fifth weeks.Conclusion: There was improvement in delayed union fracture healing after the administration of ELF-PEMF as seen from the difference in Rust score and load score."

"Pendahuluan: Fraktur akibat kecelakaan merupakan masalah kesehatan yang menduduki peringkat ke sembilan secara global dan diperkirakan akan menduduki peringkat ketiga pada tahun 2030. Dari seluruh kasus fraktur, kejadian delayed union berkisar antara 5-10%. Delayed union menimbulkan disabilitas, penurunan kualitas hidup, dan peningkatan biaya pengobatan. Saat ini, penanganan delayed union terbaik dengan bone graft masih terbatas persediaannya. Terapi mutakhir penanganan delayed union menggunakan sintesis osteoinduktif seperti BMP-2 sudah banyak diteliti dan digunakan namun biayanya sangat mahal. Penelitian ini bertujuan untuk mengetahui efektifitas citrus flavonoid dalam meningkatkan ekspresi BMP-2 dan VEGF sehingga dapat meningkatkan kualitas fracture healing pada model delayed union hewan coba tikus Sprague-Dawley.Material dan Metode: Uji eksperimental ini menggunakan 30 tikus Sprague-Dawley yang menjadi model delayed union dengan perlakuan stripping periosteum. Tikus dibagi ke dalam 3 kelompok, yaitu kelompok kontrol, kelompok yang diberikan citrus flavonoid 250 mcg, dan kelompok yang diberikan citrus flavonoid 500 mcg. Tikus dieuthanasia pada hari ke-15 dan hari ke-30 untuk melihat profil histomorfometrik, ekspresi BMP-2, dan ekspresi VEGF melalui aplikasi ImageScope.Hasil: Pada penelitian ini didapatkan area penulangan yang secara bermakna lebih luas pada kelompok 250 mcg dibandingkan dengan kelompok kontrol (p = 0.047) dan juga pada kelompok 500 mcg dibandingkan dengan kelompok kontrol (p = 0.047) pada hari ke-15. Pembentukan kalus pada hari ke-15 juga ditemukan lebih cepat pada kelompok 250 mcg dan kelompok 500 mcg dibandingkan dengan kontrol (p = 0.009, p = 0.009). Ekspresi BMP-2 paling tinggi didapatkan pada kelompok 250 mcg. BMP-2 secara bermakna lebih besar pada kelompok 250 mcg dibandingkan dengan kelompok kontrol baik pada hari ke-15 maupun hari ke-30 (p < 0.05). Selain itu, ekspresi BMP-2 pada kelompok 500 mcg juga ditemukan secara bermakna lebih besar dibandingkan kelompok kontrol namun hanya pada hari ke-30. Ekspresi VEGF terbesar didapatkan pada kelompok 500 mcg dengan perbandingan yang secara signifikan lebih besar daripada kelompok kontrol dan 250 mcg (p < 0.05). Penelitian ini menunjukkan ekspresi BMP-2 yang memiliki dosis terapeutik terbaik di 250 mcg dengan penambahan dosis yang menimbulkan efek negative pada produksi BMP-2. Selain itu, ekspresi VEGF ditemukan paling baik pada dosis 500 mcg sehingga terdapat perbaikan penyembuhan fraktur baik pada kelompok 250 mcg maupun 500 mcg.Kesimpulan: Citrus flavonoid meningkatkan penyembuhan fraktur melalui peningkatan ekspresi BMP-2 dan VEGF. Terjadi mekanisme negative feedback dari BMP-2 pada pemberian citrus flavonoid yang berlebihan.

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Introduction: Fracture due to traffic accidents is ranked ninth among other problems in health sector and projected to be ranked third in 2030. Delayed union accounts for 5-10% of all fractures. It causes disability, lower quality of life, and increased cost of treatment. Currently, the ideal treatments of delayed union using bone graft application is still limited and sometimes inaccessible. Advanced alternative treatments using BMP-2 synthetics as osteoinductive factors is currently too expensive although it has been clinically proven by previous literatures. This study aimed to discover the effectivity of citrus flavonoid in increasing the expression of BMP-2 and VEGF to accelerate the fracture healing process of delayed union models of Sprague-Dawley rats.

Methods: This experimental study used 30 Sprague-Dawley rats that underwent periosteal stripping to create delayed union models. Subjects were allocated into three groups, namely control group, group with 250 mcg citrus flavonoid initial administration, and group with 500 mcg citrus flavonoid initial administration. The subjects were sacrificed in day 15 and day 30 to observe the histomorphometric profile, BMP-2 expression, and VEGF expression using ImageScope application.

Results: The area of lamellar bone was observed significantly higher in 250 mcg and 500 mcg groups compared to control group on day 15 (p = 0.047). The callus area showed similar result and significantly higher area were observed in 250 mcg and 500 mcg groups compared to control on day 15 (p = 0.009, p = 0.009). The highest BMP-2 expression was observed in 250 mcg group. Statistical test showed significant difference between 250 mcg with 500 mcg and 250 mcg with control groups (p < 0.05). The highest VEGF expression was seen in 500 mcg group, also with significant difference between 500 mcg group compared with 250 mcg and control on day 15. This study found the best therapeutic dose for BMP-2 was 250 mcg while the best therapeutic dose for VEGF was 500 mcg. Excessive addition of citrus flavonoid caused negative impact on BMP-2 expression. Markedly accelerated fracture healing was observed in both 250 mcg and 500 mcg groups.

Conclusion: Citrus flavonoid accelerated the fracture healing process by increasing the expression of BMP-2 and VEGF. There is a negative feedback mechanism of BMP-2 expression when excessive dose of citrus flavonoid was given."