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Tesis ini bertujuan untuk menganalisis hasil studi-studi terdahulu mengenai keberhasilan tatalaksana implan gigi pada pasien dengan konsumsi bisfosfonat, baik berdasarkan cara pemberian bisfosfonat, maupun pengaruh waktu pemberian bisfosfonat terhadap keberhasilan tatalaksana implan gigi. Penelitian ini merupakan sebuah systematic review dengan desain deskriptif. Hasil penelitian ini menunjukkan bahwa keberhasilan implan pada pasien dengan konsumsi bisfosfonat cukup tinggi, baik berdasarkan cara pemberian maupun waktu pemasangan implan gigi terhadap waktu pemberian bisfosfonat; tidak semua pasien yang mengkonsumsi bisfosfonat akan mengalami osteonecrosis of the jaw.

 

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This study aims to analyze the results of previous studies on the successful management of dental implants in patients with bisphosphonate consumption, both based on the way bisphosphonates are administered, as well as the effect of the time of bisphosphonate administration on the successful management of dental implants. This study is a systematic review with a descriptive design. The results of this study indicate that the success of implants in patients with bisphosphonate consumption is quite high, both based on the way they are administered and when the dental implants are placed against the time of bisphosphonate administration; not all patients taking bisphosphonates will experience osteonecrosis of the jaw.

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"Pendahuluan Beberapa penelitian melaporkan bahwa injeksi Zoledronate Bisphosphonate (ZOL) mampu menghambat pergerakan gigi ortodonti, namun pemberian secara injeksi menimbulkan rasa sakit. Penggunaan emulsi ZOL dengan minyak zaitun dalam gel (Ge-ZOL) diharapkan dapat mengatasi kekurangan pemberian ZOL secara injeksi tersebut. Dalam kedokteran gigi belum ada Ge-ZOL dan belum diketahui efeknya terhadap apoptosis sel osteoklas.Tujuan Untuk membuktikan efek paparan Ge-ZOL dengan minyak zaitun terhadap jumlah apoptosis sel osteoklas.Metode Desain penelitian adalah eksperimental laboratorik in vivo. Penelitian menggunakan 27 tikus Sprague Dawley, 9 tikus eksperimental menerima Ge-ZOL dengan minyak zaitun kadar 40 µg/mL, 9 tikus kontrol mendapatkan Ge- dan 9 tikus normal. Mukosa bukal regio mesial molar satu bawah kanan tikus dioleskan gel pada jam awal, keempat dan kedelapan, selama dua menit pada hari ke-1, 2, 3 dan 4. Tikus disacrifice pada hari ke-1, 3 dan 5, dibuat sediaan histologi dengan pewarnaan IHK Caspase-3.Hasil Ge-ZOL meningkatkan jumlah apoptosis sel osteoklas pada hari ke-1 dan 3 serta peningkatan tertinggi terdapat pada hari ke-3. Pada hari ke-5 terjadi penurunan jumlah apoptosis sel osteoklas.Kesimpulan Ge-ZOL dengan minyak zaitun dosis 40 µg terbukti mampu meningkatkan jumlah apoptosis sel osteoklas.

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Introduction Several studies have reported that injection of Zoledronate Bisphosphonate (ZOL) could inhibit orthodontic tooth movement, but the administration by injection is painless. Use of ZOL emulsion with olive oil in a gel (Ge-ZOL) is expected to overcome the lack of administration by injection. In dentistry, until recently there is no Ge-ZOL and its effect on apoptosis osteoclast is still unknown.Objective To proved the effects of exposure of Ge-ZOL with olive oil on the number of osteoclasts apoptosis.Methods The study design was an experimental laboratory in vivo. The study used 27 Sprague Dawley rats consist of 9 rats experimental group received Ge-ZOL, 9 rats control group receive control gel and 9 rats of normal groups. The gel was applied on mesial buccal mucosa of lower right first molar on beginning, hours to four to eight for two minutes on days 1, 2, 3 and 4. Rats were sacrificed on days 1, 3, 5 and then made preparation histological staining with IHK Caspase-3.Results Ge-ZOL could increase the number of osteoclasts apoptosis on day 1 and 3 as well as the highest increase on the 3rd day.Conclusion Ge-ZOL with olive oil dose of 40 µg proven to increase the number of osteoclast apoptosis."

"The Effect of Bisphosphonate on The Osteoclast-Like Cell Formation In A Mouse Bone Marrow CultureBisphosphonates are reported to have an inhibitory effect on bone resorption in vivo and in vitro. The present study examined the effect of bisphosphonate on the formation of osteoclast-like cells in vitro. When mouse bone marrow cells were cultured for 8 days with 10$M la, 25-dihydroxyvitamin D3 (la, 25(OH)2 D3) numerous clusters of mononuclear and multinucleated cells formed, which stained positive for tartrate-resistant acid phosphatase (TRAP-positive). la, 25(011)2 D3 is known to stimulate osteoclast-like cell formation in a mouse bone marrow culture. Adding 1-hydroxyethylidene-l, 1-bisphosphonate (BEEP) inhibited the increased formation of osteoclast-like cells stimulated by this stimulant. A time-course experimental model showed that the number of osteoclast-like cells decreased slightly when drugs were given early in the culture period and decreased markedly when the drugs were given later or continuously in the culture period.These findings suggested that bisphosphonate had an effect on mature stage and significantly inhibit bone destruction by inhibit osteoclast-like cells formation. The amount of PGE2 production stimulated by la, 25(011)2 D3 was dose dependently higher with BEEP and 3-amino-lhydroxypropylidene-1, 1-bisphosphonate (APD). Showing that PGE2 production is high at the end of culture when the cells are going to undergo apoptosis. This showed in part, the known bone-resorbing activity of these agents."

"ABSTRAKPendahuluan: Pada penelitian yang telah dilakukan sebelumnya, zoledronate bisphosphonate dalam bentuk gel emulsi telah terbukti meningkatkan jumlah apoptosis sel osteoklas. Aplikasi topikal dalam bentuk gel telah banyak digunakan pada rongga mulut. Tujuan dari penelitian ini adalah untuk mengetahui stabilitas fisik gel zoledronate bisphosphonate sebagai salah satu syarat dalam pengembangan produk baru.Metode: Formulasi gel zoledronate dibuat dari carboxylmethylcellulose (CMC), gliserin, dan sodium benzoat dengan dosis 40 μg zoledronate dalam setiap 25 mg gel. Gel disimpan pada suhu 25°C dan 40°C selama 28 hari dan dievaluasi viskositas, pH, daya sebar, daya lekat, dan kadar obat pada awal, hari ke-7, hari ke-14, dan hari ke-28.Hasil: Pada penyimpanan suhu 25°C, uji repeated measure ANOVA menunjukkan tidak terdapat perbedaan bermakna secara statistik pada parameter viskositas, daya sebar, dan daya lekat antar waktu penyimpanan (p>0,05). Pada parameter kadar obat dan pH, terdapat perbedaan yang bermakna secara statistik (p<0,05) namun secara kuantatif masih dalam batas normal. Sementara pada hari ke-28 penyimpanan suhu 40°C, gel mengeras sehingga pengujian hanya dilakukan pada hari ke-7 dan ke-14. Terdapat perbedaan yang bermakna secara statistik pada semua parameter uji stabilitas (p<0,05) antar waktu pengamatan pada suhu 40°C. Hasil uji t-test independent menunjukkan tidak terdapat perbedaan bermakna secara statistik pada semua parameter (p>0,05) antar suhu penyimpanan pada hari ke-7 dan ke-14.Kesimpulan: Nilai viskositas, daya sebar, daya lekat, kadar obat, dan pH gel zoledronate stabil selama 28 hari pada suhu penyimpanan 25°C. Pada suhu 40°C setelah hari ke-14, gel zoledronate menjadi tidak stabil karena konsistensi gel mengeras pada hari ke-28.

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ABSTRACT

Introduction: In the previous study, topical application of zoledronate bisphosphonate in gel emulsion has been proven to increase the number of osteoclasts apoptosis. In the oral cavity, topical application is commonly used in gel form; therefore, this study was conducted to evaluate the physical stability of zoledronate bisphosphonate in gel form as one of the prerequisites in developing a new drug product.

Methods: The gel formulation was prepared using carboxylmethylcellulose (CMC), glycerine, and sodium benzoate in a dosage form of 40 μg zoledronate in every 25 mg gel. The gels were stored at 25°C and 40°C for 28 days and evaluated for viscosity, pH value, spreadability, adhesive strength, and drug content on the 1st day, 7th day, 14th day, and 28th day.

Results: At the 25°C of storage, repeated measure ANOVA test shows no statistically significant changes in viscosity, spreadability, and adhesive strength between the 7th, 14th, and 28th day (p>0,05). The changes in drug content and pH value were statistically significant (p<0,05) but quantitatively still in the normal range. Meanwhile, on the 28th day at the 40°C of storage, the gel hardened; therefore, the stability test could only be performed on the 7th and 14th day. There were statistically significant changes in all parameters (p<0,05) between the 7th, 14th, and 28th day at 40°C. The t-test independent shows no statistically significant changes in all parameters (p>0,05) between the 25°C and 40°C of storage on the 7th and 14th day.

Conclusion: The zoledronate bisphosphonate gel was stable in viscosity, spreadability, adhesive strength, drug content, and pH value at 25°C for 28 days. At 40°C of storage, zoledronate gel was unstable after 14 days because the consistency of the gel hardened on the 28th day."

"During the early 19th century, it was discovered that adding yellow (now called white) phosphorous to matchstick heads made it easier to ignite matches. The phosphorous vapors were breathed in by workers and combined with other chemicals in the body to produce a potent nitrogen-containing bisphosphonate. Today's oral nitrogen-containing bisphosphonates and intravenous nitrogen-containing bisphosphonates circulate around the body the same way as the phosphorous vapors, and are absorbed into bone and ingested by osteoclasts. When this unique binding process of bisphosphonates to bone occurs, osteoclasts are poisoned, and this reduces or eliminates bone turnover. Alveolar bone in the mandible and maxilla turns over more rapidly than in long bones, so the jaws are a better target for bisphosphonate toxicity. It wasn't until 2003 that today's intravenous and oral nitrogen-containing bisphosphonate medications were implicated as major risk factors in the development of exposed necrotic bone of the jaws. Most of the researchers who reported cases of bisphosphonate-induced osteonecrosis of the jaw found that these patients were treated with zoledronate, pamidronate, or a combination of these drugs, which are commonly used for treating breast cancer or myeloma. In about 5% of cases, subjects with BIONJ were being treated for osteoporosis. Precipitating events that contribute to BIONJ are tooth extractions (about 50% of cases), mandibular exostoses, periodontal disease, and local trauma from ill-fitting dentures. It is not known if the placement of dental implants is a precipitating factor. The book aims to meet the need of medical practitioners working in all fields that use bisphosphonates, and to present the conservative and surgical treatment methods currently in use. There will also be detailed information on the literature relating to dental implants in patients treated with bisphosphonates."