臺灣博碩士論文加值系統

本研究的主要目的是找尋服用抗骨吸收藥物、或者發生藥物相關之顎骨壞死的病人放射學影像之客觀量測數據。以期透過這些客觀數據協助醫師早期診斷、擬定治療策略及計畫。資料來源透過回溯性的方式搜集使用藥物前後的環口全景X光影像、以及發生藥物相關之顎骨壞死之錐狀束電腦斷層，分別使用碎形維度以及測量皮質骨厚度並觀察其變化程度與藥物相關之顎骨壞死之發生、藥物種類、藥物使用時間、原發癌症的關係。以目前結果來說，可發現使用抗骨吸收藥物後碎形維度有顯著上升的趨勢，但若發生藥物相關之顎骨壞死碎形維度反而會顯著下降。皮質骨厚度則是於特定區域會呈現相對於控制組有顯著上升的趨勢。這些發現可提供現階段對於服用抗骨吸收藥物、或者發生藥物相關之顎骨壞死的病人另一些客觀數據的評估。但受限於回溯性的研究設計，仍有部分組別無法將條件控制完善，還需要往後更多相關研究來佐證及應用。

The main purpose of this study is to identify objective radiographic measurements in patients who have taken anti-resorptive agents or experienced medication-related osteonecrosis of the jaw (MRONJ). The objective data collected through this study is intended to assist physicians in early diagnosis, treatment planning, and strategy development. The data was retrospectively collected from panoramic radiographs taken before and after drug use and cone-beam computed tomography scans taken after the occurrence of MRONJ. Fractal dimension and cortical bone thickness measurements were used to observe their changes in relation to occurrence of MRONJ, drug type, duration of use, and primary cancer. The results thus far indicate a significant increase in fractal dimension after using anti-resorptive drugs, but a significant decrease in fractal dimension when MRONJ occurs. Moreover, cortical bone thickness shows a significant increase in certain regions compared to the control group. These findings provide additional objective data for evaluating patients who have taken anti-resorptive drugs or experienced MRONJ. However, the retrospective study design is limited, and some groups were not able to control for certain conditions adequately, indicating a need for further relevant research to confirm and apply the findings.

目 錄
口試委員審定書 i
誌謝 ii
摘要 iii
Abstract iv
圖目錄 vii
表目錄 viii
第一章 引言與文獻回顧 1
1.1 本章摘要 1
1.2 抗骨吸收藥物（Anti-resorptive agents） 1
1.3 藥物相關性顎骨壞死（Medication-related osteonecrosis of jaw, MRONJ） 1
1.4 服用抗骨吸收藥物及藥物相關顎骨壞死影像學上的變化 2
1.5 碎形維度（Fractal dimension）分析 2
1.6 下顎骨皮質骨厚度 3
第二章 實驗設計與方法 4
2.1 本章摘要 4
2.2 研究目的 4
2.3 影像資料來源 4
2.4 資料排除 4
2.5 研究組別 5
2.5.1 環口全景X光 5
2.5.2 錐狀束電腦斷層 5
2.6 測量方式 6
2.6.1 碎形維度 6
2.6.2 下顎皮質骨厚度 6
2.7 觀察者內信度（Intra-observer reliability） 7
2.8 統計方式 7
第三章 實驗結果 8
3.1 本章概要 8
3.2 觀察者內信度 8
3.3 環口全景X光-惡性腫瘤-BP組別-用藥前後FD差異 8
3.4 環口全景X光-惡性腫瘤-BP組別-用藥前後FD差異-以ROI位置做次群組分析 8
3.5 環口全景X光-惡性腫瘤-DMB組別-用藥前後FD差異 9
3.6 環口全景X光-惡性腫瘤-DMB組別-用藥前後FD差異-以ROI位置做次群組分析 9
3.7 環口全景X光-惡性腫瘤-BP組別- BPz+ONJ- vs BPz+ONJ+ vs Control (BP-) 的FD值比較 9
3.8 環口全景X光-惡性腫瘤-DMB組別-DMBx+ONJ- vs DMBx +ONJ+ vs Control (DMB-)的FD值比較 9
3.9 環口全景X光-骨質疏鬆- BPF+ONJ- vs BPF+ONJ+ vs Control 的FD值比較 10
3.10 環口全景X光-骨質疏鬆 - DMBp+ONJ- vs DMBp +ONJ+ vs Control的FD值比較 10
3.11 錐狀束電腦斷層-惡性腫瘤-不同藥物與對照組皮質骨厚度之分析 10
3.12 錐狀束電腦斷層-惡性腫瘤-Zometa藥物 11
3.13 錐狀束電腦斷層-惡性腫瘤-Xgeva藥物 11
3.14 錐狀束電腦斷層-骨質疏鬆-不同藥物與對照組皮質骨厚度之分析 11
3.15 錐狀束電腦斷層-骨質疏鬆-Fosamax藥物 11
3.16 錐狀束電腦斷層 - 惡性腫瘤-Zometa藥物-ONJ處皮質骨厚度與相對處之比較 12
3.17 錐狀束電腦斷層 - 惡性腫瘤- Xgeva藥物-ONJ處皮質骨厚度與相對處之比較 12
3.18 錐狀束電腦斷層 – 骨質疏鬆-Fosamax藥物-ONJ處皮質骨厚度與相對處之比較 12
第四章 討論 13
4.1 環口全景X光-惡性腫瘤 13
4.2 環口全景X光-骨質疏鬆 14
4.3 錐狀束電腦斷層 14
4.4 本實驗之限制及困難 14
第五章 結論 16
參考資料 64

Alman, A., Johnson, L., Calverley, D., Grunwald, G., Lezotte, D., & Hokanson, J. (2012). Diagnostic capabilities of fractal dimension and mandibular cortical width to identify men and women with decreased bone mineral density. Osteoporosis International, 23, 1631-1636.
Bachtler, R., Walter, C., & Schulze, R. K. (2021). Fractal dimension in CBCT images as predictor for MRONJ: a retrospective cohort study. Clinical oral investigations, 25, 2113-2118.
Bagan, J., Cibrian, R., Lopez, J., Leopoldo-Rodado, M., Carbonell, E., Bagán, L., Utrilla, J., & Scully, C. (2015). Sclerosis in bisphosphonate-related osteonecrosis of the jaws and its correlation with the clinical stages: study of 43 cases. British Journal of Oral and Maxillofacial Surgery, 53(3), 257-262.
Baron, R., Ferrari, S., & Russell, R. G. G. (2011). Denosumab and bisphosphonates: different mechanisms of action and effects. Bone, 48(4), 677-692.
Cavalcante, D. d. S., Silva, P. G. d. B., Carvalho, F. S. R., Quidute, A. R. P., Kurita, L. M., Cid, A. M. P. L., Ribeiro, T. R., Gurgel, M. L., Kurita, B. M., & Costa, F. W. G. (2022). Is jaw fractal dimension a reliable biomarker for osteoporosis screening? A systematic review and meta-analysis of diagnostic test accuracy studies. Dentomaxillofacial Radiology, 51(4), 20210365.
Demiralp, K. Ö., Kurşun-Çakmak, E. Ş., Bayrak, S., Akbulut, N., Atakan, C., & Orhan, K. (2019). Trabecular structure designation using fractal analysis technique on panoramic radiographs of patients with bisphosphonate intake: a preliminary study. Oral Radiology, 35, 23-28.
Huang, C., Chen, J., Chang, Y., Jeng, J., & Chen, C. (2013). A fractal dimensional approach to successful evaluation of apical healing. International endodontic journal, 46(6), 523-529.
Kato, C. N., Barra, S. G., Tavares, N. P., Amaral, T. M., Brasileiro, C. B., Mesquita, R. A., & Abreu, L. G. (2020). Use of fractal analysis in dental images: a systematic review. Dentomaxillofacial Radiology, 49(2), 20180457.
Kim, J.-E., Yoo, S., & Choi, S.-C. (2020). Several issues regarding the diagnostic imaging of medication-related osteonecrosis of the jaw. Imaging Science in Dentistry, 50(4), 273.
Kimmel, D. (2007). Mechanism of action, pharmacokinetic and pharmacodynamic profile, and clinical applications of nitrogen-containing bisphosphonates. Journal of dental research, 86(11), 1022-1033.
Koo, C.-H., & Lee, J.-H. (2018). Evaluation of mandibular cortical bone ratio on computed tomography images in patients taking bisphosphonates. Maxillofacial Plastic and Reconstructive Surgery, 40, 1-7.
Kotze, M. J., Bütow, K.-W., Olorunju, S. A., & Kotze, H. F. (2014). A comparison of mandibular and maxillary alveolar osteogenesis over six weeks: a radiological examination. Head & Face Medicine, 10(1), 1-7.
Mandelbrot, B. B. (1985). Self-affine fractals and fractal dimension. Physica scripta, 32(4), 257.
Moreno-Rabié, C., Gaêta-Araujo, H., Oliveira-Santos, C., Politis, C., & Jacobs, R. (2020). Early imaging signs of the use of antiresorptive medication and MRONJ: a systematic review. Clinical oral investigations, 24, 2973-2989.
Ruggiero, S. L., Dodson, T. B., Aghaloo, T., Carlson, E. R., Ward, B. B., & Kademani, D. (2022). American Association of Oral and Maxillofacial Surgeons’ Position Paper on medication-related osteonecrosis of the jaw–2022 update. Journal of oral and maxillofacial surgery.
Russell, R. G. G., Xia, Z., Dunford, J. E., Oppermann, U., Kwaasi, A., Hulley, P. A., Kavanagh, K. L., Triffitt, J. T., Lundy, M. W., & Phipps, R. J. (2007). Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Annals of the New York Academy of Sciences, 1117(1), 209-257.
Sindeaux, R., de Souza Figueiredo, P. T., de Melo, N. S., Guimarães, A. T. B., Lazarte, L., Pereira, F. B., de Paula, A. P., & Leite, A. F. (2014). Fractal dimension and mandibular cortical width in normal and osteoporotic men and women. Maturitas, 77(2), 142-148.
Tolga Suer, B., Yaman, Z., & Buyuksarac, B. (2016). Correlation of Fractal Dimension Values with Implant Insertion Torque and Resonance Frequency Values at Implant Recipient Sites. International Journal of Oral & Maxillofacial Implants, 31(1).
Torres, S., Chen, C., Leroux, B., Lee, P., Hollender, L., & Schubert, M. (2011). Fractal dimension evaluation of cone beam computed tomography in patients with bisphosphonate-associated osteonecrosis. Dentomaxillofacial Radiology, 40(8), 501-505.
Torres, S. R., Chen, C. S., Leroux, B. G., Lee, P. P., Hollender, L. G., Lloid, M., Drew, S. P., & Schubert, M. M. (2015). Mandibular inferior cortical bone thickness on panoramic radiographs in patients using bisphosphonates. Oral surgery, oral medicine, oral pathology and oral radiology, 119(5), 584-592.
White, S. C., & Rudolph, D. J. (1999). Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 88(5), 628-635.