Skip to content

pdt_references.md

Latest commit

 

History

History
238 lines (179 loc) · 26.1 KB

pdt_references.md

File metadata and controls

238 lines (179 loc) · 26.1 KB
Raw

치주염 QSP 모델 참고문헌 (Periodontitis QSP Model — References)

각 항목은 모델의 어느 부분을 지지하는지 함께 표기했습니다. Each entry notes which part of the model it supports.

1. 병인론의 틀 — 폴리마이크로비얼 시너지·디스바이오시스 (PSD) 모델

이 모델의 미생물 구획 구조(공생균 · 디스바이오틱 균 · 키스톤 병원체를 분리한 3층 구조)와 KEY = 1 + EKEY·PG/(KMKEY+PG) 형태의 저농도 고레버리지 항의 근거.

  1. Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012;10(10):717-25. https://pubmed.ncbi.nlm.nih.gov/22941505/
  2. Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol. 2012;27(6):409-19. https://pubmed.ncbi.nlm.nih.gov/23134607/
  3. Hajishengallis G, Liang S, Payne MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497-506. https://pubmed.ncbi.nlm.nih.gov/22036469/
  4. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25(2):134-44. https://pubmed.ncbi.nlm.nih.gov/9495612/
  5. Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010;8(7):481-90. https://pubmed.ncbi.nlm.nih.gov/20514045/
  6. Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16(12):745-59. https://pubmed.ncbi.nlm.nih.gov/30301974/
  7. Abusleme L, Dupuy AK, Dutzan N, et al. The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J. 2013;7(5):1016-25. https://pubmed.ncbi.nlm.nih.gov/23303375/

2. 염증친화적(inflammophilic) 영양 되먹임 — 모델의 엔진

NUTR(GCF 유래 영양) → 디스바이오틱 균 성장 항의 근거. 이 되먹임이 loop gain > 1을 만들어 쌍안정성(bistability)을 낳는다는 것이 이 모델의 첫 번째 조직 원리입니다.

  1. Hajishengallis G. The inflammophilic character of the periodontitis-associated microbiota. Mol Oral Microbiol. 2014;29(6):248-57. https://pubmed.ncbi.nlm.nih.gov/24976068/
  2. Herrero ER, Fernandes S, Verspecht T, et al. Dysbiotic biofilms deregulate the periodontal inflammatory response. J Dent Res. 2018;97(5):547-55. https://pubmed.ncbi.nlm.nih.gov/29303019/
  3. Smalley JW, Olczak T. Haem acquisition mechanisms of Porphyromonas gingivalis — strategies used in a polymicrobial community in a haem-limited host environment. Mol Oral Microbiol. 2017;32(1):1-23. https://pubmed.ncbi.nlm.nih.gov/26662717/
  4. Griffiths GS. Formation, collection and significance of gingival crevice fluid. Periodontol 2000. 2003;31:32-42. https://pubmed.ncbi.nlm.nih.gov/12656994/

3. 키스톤 병원체 병독성 — 진지페인, LPS 이질성, 조직 침습

GING(진지페인 활성), 진지페인의 C5 전환효소 유사 활성(C3 비의존 C5a 생성), 조직 침습 분획(TISS_FRAC)의 근거.

  1. Potempa J, Sroka A, Imamura T, Travis J. Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis. Curr Protein Pept Sci. 2003;4(6):397-407. https://pubmed.ncbi.nlm.nih.gov/14683426/
  2. Wingrove JA, DiScipio RG, Chen Z, Potempa J, Travis J, Hugli TE. Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas gingivalis. J Biol Chem. 1992;267(26):18902-7. https://pubmed.ncbi.nlm.nih.gov/1527018/
  3. Coats SR, Jones JW, Do CT, et al. Human Toll-like receptor 4 responses to P. gingivalis are regulated by lipid A 1- and 4'-phosphatase activities. Cell Microbiol. 2009;11(11):1587-99. https://pubmed.ncbi.nlm.nih.gov/19552698/
  4. Lamont RJ, Chan A, Belton CM, Izutsu KT, Vasel D, Weinberg A. Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun. 1995;63(10):3878-85. https://pubmed.ncbi.nlm.nih.gov/7558295/
  5. Wegner N, Wait R, Sroka A, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and alpha-enolase. Arthritis Rheum. 2010;62(9):2662-72. https://pubmed.ncbi.nlm.nih.gov/20506214/
  6. Kachlany SC. Aggregatibacter actinomycetemcomitans leukotoxin: from threat to therapy. J Dent Res. 2010;89(6):561-70. https://pubmed.ncbi.nlm.nih.gov/20200418/
  7. Haubek D, Ennibi OK, Poulsen K, Væth M, Poulsen S, Kilian M. Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of A. actinomycetemcomitans in Morocco: a prospective longitudinal cohort study. Lancet. 2008;371(9608):237-42. https://pubmed.ncbi.nlm.nih.gov/18207019/

4. 보체–TLR2 교차대화와 호중구 살균능 전복 — 모델의 두 번째 조직 원리

살균능(PKILL)을 상수가 아닌 상태변수로 둔 근거, SUBV 항의 Hill 형태, 그리고 세균 제거를 PMN × PKILL에 비례시킨 구조의 근거.

  1. Maekawa T, Krauss JL, Abe T, et al. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe. 2014;15(6):768-78. https://pubmed.ncbi.nlm.nih.gov/24922578/
  2. Wang M, Krauss JL, Domon H, et al. Microbial hijacking of complement-Toll-like receptor crosstalk. Sci Signal. 2010;3(109):ra11. https://pubmed.ncbi.nlm.nih.gov/20159852/
  3. Hajishengallis G, Lambris JD. Microbial manipulation of receptor crosstalk in innate immunity. Nat Rev Immunol. 2011;11(3):187-200. https://pubmed.ncbi.nlm.nih.gov/21331082/
  4. Hajishengallis G, Lambris JD. Complement and dysbiosis in periodontal disease. Immunobiology. 2012;217(11):1111-6. https://pubmed.ncbi.nlm.nih.gov/22964237/
  5. Hajishengallis G, Chavakis T, Hajishengallis E, Lambris JD. Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. J Leukoc Biol. 2015;98(4):539-48. https://pubmed.ncbi.nlm.nih.gov/25548253/
  6. Hajishengallis G, Moutsopoulos NM, Hajishengallis E, Chavakis T. Immune and regulatory functions of neutrophils in inflammatory bone loss. Semin Immunol. 2016;28(2):146-58. https://pubmed.ncbi.nlm.nih.gov/26936034/

5. 호중구 결핍의 역설 — LAD-I와 IL-17

LADI 스위치가 호중구 동원을 없애면서도 IL-17을 통해 골소실을 악화시키는 구조의 근거.

  1. Moutsopoulos NM, Konkel J, Sarmadi M, et al. Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med. 2014;6(229):229ra40. https://pubmed.ncbi.nlm.nih.gov/24670684/
  2. Moutsopoulos NM, Zerbe CS, Wild T, et al. Interleukin-12 and interleukin-23 blockade in leukocyte adhesion deficiency type 1. N Engl J Med. 2017;376(12):1141-6. https://pubmed.ncbi.nlm.nih.gov/28328334/
  3. Dutzan N, Kajikawa T, Abusleme L, et al. A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans. Sci Transl Med. 2018;10(463):eaat0797. https://pubmed.ncbi.nlm.nih.gov/30333238/
  4. Dutzan N, Abusleme L, Bridgeman H, et al. On-going mechanical damage from mastication drives homeostatic Th17 cell responses at the oral barrier. Immunity. 2017;46(1):133-47. https://pubmed.ncbi.nlm.nih.gov/28087239/

6. RANKL/OPG와 골소실 — 모델의 래칫

RANKL_T의 세포 출처 가중치(Th17 · B/형질세포 · 기질세포), RATIO^HOC 파골세포 구동, 그리고 BLOSS를 단조 증가 적분으로 둔 구조의 근거.

  1. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337-42. https://pubmed.ncbi.nlm.nih.gov/12748652/
  2. Kawai T, Matsuyama T, Hosokawa Y, et al. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006;169(3):987-98. https://pubmed.ncbi.nlm.nih.gov/16936272/
  3. Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol. 2012;39(3):239-48. https://pubmed.ncbi.nlm.nih.gov/22092994/
  4. Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003;74(3):391-401. https://pubmed.ncbi.nlm.nih.gov/12710761/
  5. Waerhaug J. The angular bone defect and its relationship to trauma from occlusion and downgrowth of subgingival plaque. J Clin Periodontol. 1979;6(2):61-82. https://pubmed.ncbi.nlm.nih.gov/286657/
  6. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976;34(3):235-49. https://pubmed.ncbi.nlm.nih.gov/765622/

7. MMP–TIMP 불균형과 결합조직 파괴

MMP8A(활성 MMP-8)를 총량이 아닌 활성으로 계산하고 doxycycline이 합성이 아닌 활성을 억제하도록 둔 구조의 근거.

  1. Sorsa T, Tjäderhane L, Konttinen YT, et al. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 2006;38(5):306-21. https://pubmed.ncbi.nlm.nih.gov/16938801/
  2. Golub LM, Lee HM, Ryan ME, Giannobile WV, Payne J, Sorsa T. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv Dent Res. 1998;12(2):12-26. https://pubmed.ncbi.nlm.nih.gov/9972117/
  3. Sorsa T, Alassiri S, Grigoriadis A, et al. Active MMP-8 (aMMP-8) as a grading and staging biomarker in the periodontitis classification. Diagnostics (Basel). 2020;10(2):61. https://pubmed.ncbi.nlm.nih.gov/31979091/
  4. Uitto VJ, Overall CM, McCulloch C. Proteolytic host cell enzymes in gingival crevice fluid. Periodontol 2000. 2003;31:77-104. https://pubmed.ncbi.nlm.nih.gov/12656997/

8. 해소(resolution) 실패와 SPM

RVELOC(resolvin E1) 구획, 호중구 동원 억제 + 효율적 사멸세포 제거(efferocytosis) 증강이라는 비면역억제성 작용 방식의 근거.

  1. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510(7503):92-101. https://pubmed.ncbi.nlm.nih.gov/24899309/
  2. Hasturk H, Kantarci A, Goguet-Surmenian E, et al. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol. 2007;179(10):7021-9. https://pubmed.ncbi.nlm.nih.gov/17982093/
  3. Van Dyke TE. Pro-resolving mediators in the regulation of periodontal disease. Mol Aspects Med. 2017;58:21-36. https://pubmed.ncbi.nlm.nih.gov/28483532/
  4. Van Dyke TE, Hasturk H, Kantarci A, et al. Proresolving nanomedicines activate bone regeneration in periodontitis. J Dent Res. 2015;94(1):148-56. https://pubmed.ncbi.nlm.nih.gov/25389003/

9. 기계적 치료 — 깊이 의존성이 해부학적이라는 근거

SRP_EFF 로지스틱(PPD50_SRP = 5.8 mm, PPD_W = 1.5 mm)의 직접적 데이터 출처. 모델은 3.0 / 4.5 / 6.5 mm에서 각각 82% / 63% / 34% 결석 제거를 예측하며 Waerhaug의 실측치는 83% / 61% / 32%입니다.

  1. Waerhaug J. Healing of the dento-epithelial junction following subgingival plaque control. II. As observed on extracted teeth. J Periodontol. 1978;49(3):119-34. https://pubmed.ncbi.nlm.nih.gov/347090/
  2. Rabbani GM, Ash MM, Caffesse RG. The effectiveness of subgingival scaling and root planing in calculus removal. J Periodontol. 1981;52(3):119-23. https://pubmed.ncbi.nlm.nih.gov/6939862/
  3. Stambaugh RV, Dragoo M, Smith DM, Carasali L. The limits of subgingival scaling. Int J Periodontics Restorative Dent. 1981;1(5):30-41. https://pubmed.ncbi.nlm.nih.gov/7047430/
  4. Cobb CM. Non-surgical pocket therapy: mechanical. Ann Periodontol. 1996;1(1):443-90. https://pubmed.ncbi.nlm.nih.gov/9118261/
  5. Cobb CM. Clinical significance of non-surgical periodontal therapy: an evidence-based perspective of scaling and root planing. J Clin Periodontol. 2002;29 Suppl 2:6-16. https://pubmed.ncbi.nlm.nih.gov/12010523/

10. 임계 탐침 깊이 (critical probing depth) — 모델이 재현해야 할 창발 현상

모델은 이 값들을 목적함수로 쓰지 않았고, "수술은 숙주 파라미터를 바꾸지 않고 접근성 (PPD50)만 바꾼다 + 고정된 퇴축·부착소실 비용을 지불한다"는 단 하나의 교환에서 SRP 2.13 mm / 수술 3.43 mm를 산출합니다(문헌값 2.9 / 4.2 mm).

  1. Lindhe J, Socransky SS, Nyman S, Haffajee A, Westfelt E. "Critical probing depths" in periodontal therapy. J Clin Periodontol. 1982;9(4):323-36. https://pubmed.ncbi.nlm.nih.gov/6957467/
  2. Heitz-Mayfield LJ, Trombelli L, Heitz F, Needleman I, Moles D. A systematic review of the effect of surgical debridement vs. non-surgical debridement for the treatment of chronic periodontitis. J Clin Periodontol. 2002;29 Suppl 3:92-102. https://pubmed.ncbi.nlm.nih.gov/12787211/
  3. Badersten A, Nilvéus R, Egelberg J. Effect of nonsurgical periodontal therapy. II. Severely advanced periodontitis. J Clin Periodontol. 1984;11(1):63-76. https://pubmed.ncbi.nlm.nih.gov/6363463/
  4. Sanz M, Herrera D, Kebschull M, et al. Treatment of stage I-III periodontitis — the EFP S3 level clinical practice guideline. J Clin Periodontol. 2020;47 Suppl 22:4-60. https://pubmed.ncbi.nlm.nih.gov/32383274/

11. 항생제 보조요법

EMAX_AMX/EMAX_MTZ/SYN_AM 및 "이득이 깊은 치주낭에 집중된다"는 모델 예측의 근거.

  1. van Winkelhoff AJ, Rodenburg JP, Goené RJ, Abbas F, Winkel EG, de Graaff J. Metronidazole plus amoxycillin in the treatment of Actinobacillus actinomycetemcomitans associated periodontitis. J Clin Periodontol. 1989;16(2):128-31. https://pubmed.ncbi.nlm.nih.gov/2921374/
  2. Feres M, Soares GM, Mendes JA, et al. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012;39(12):1149-58. https://pubmed.ncbi.nlm.nih.gov/23016867/
  3. Harks I, Koch R, Eickholz P, et al. Is progression of periodontitis relevantly influenced by systemic antibiotics? A clinical randomized trial. J Clin Periodontol. 2015;42(9):832-42. https://pubmed.ncbi.nlm.nih.gov/26250060/
  4. Teughels W, Feres M, Oud V, Martín C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: a systematic review and meta-analysis. J Clin Periodontol. 2020;47 Suppl 22:257-81. https://pubmed.ncbi.nlm.nih.gov/31994207/
  5. Herrera D, Matesanz P, Martín C, Oud V, Feres M, Teughels W. Adjunctive effect of locally delivered antimicrobials in periodontitis therapy: a systematic review and meta-analysis. J Clin Periodontol. 2020;47 Suppl 22:239-56. https://pubmed.ncbi.nlm.nih.gov/31912531/
  6. Williams RC, Paquette DW, Offenbacher S, et al. Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial. J Periodontol. 2001;72(11):1535-44. https://pubmed.ncbi.nlm.nih.gov/11759865/
  7. Jepsen K, Jepsen S. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol 2000. 2016;71(1):82-112. https://pubmed.ncbi.nlm.nih.gov/27045432/

12. 숙주 조절 요법 (host modulation)

SDD(저용량 독시사이클린), C3 억제제 AMY-101, 항 RANKL 제제의 근거. 모델은 AMY-101의 최대 효과가 진지페인 유래 C5a 때문에 구조적으로 제한된다고 예측합니다.

  1. Caton JG, Ciancio SG, Blieden TM, et al. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol. 2000;71(4):521-32. https://pubmed.ncbi.nlm.nih.gov/10807113/
  2. Preshaw PM, Hefti AF, Novak MJ, et al. Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planing in chronic periodontitis: a multicenter trial. J Periodontol. 2004;75(8):1068-76. https://pubmed.ncbi.nlm.nih.gov/15455734/
  3. Golub LM, Lee HM. Periodontal therapeutics: current host-modulation agents and future directions. Periodontol 2000. 2020;82(1):186-204. https://pubmed.ncbi.nlm.nih.gov/31850625/
  4. Hasturk H, Hajishengallis G, Lambris JD, Mastellos DC, Yancopoulou D. Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. 2021;131(23):e152973. https://pubmed.ncbi.nlm.nih.gov/34623331/
  5. Maekawa T, Abe T, Hajishengallis E, et al. Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. J Immunol. 2014;192(12):6020-7. https://pubmed.ncbi.nlm.nih.gov/24808362/
  6. Hajishengallis G, Kajikawa T, Hajishengallis E, et al. Complement-dependent mechanisms and interventions in periodontal disease. Front Immunol. 2019;10:406. https://pubmed.ncbi.nlm.nih.gov/30915073/
  7. Reid IR, Billington EO. Drug therapy for osteoporosis in older adults. Lancet. 2022;399(10329):1080-92. https://pubmed.ncbi.nlm.nih.gov/35279261/
  8. Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. AAOMS position paper on medication-related osteonecrosis of the jaws — 2022 update. J Oral Maxillofac Surg. 2022;80(5):920-43. https://pubmed.ncbi.nlm.nih.gov/35300956/

13. 흡연·당뇨 등 위험 수정인자

SMOKE(호중구 기능 저하 + BOP 가림), HG_GAIN(고혈당의 살균능 손상) 항의 근거.

  1. Tomar SL, Asma S. Smoking-attributable periodontitis in the United States: findings from NHANES III. J Periodontol. 2000;71(5):743-51. https://pubmed.ncbi.nlm.nih.gov/10872955/
  2. Dietrich T, Bernimoulin JP, Glynn RJ. The effect of cigarette smoking on gingival bleeding. J Periodontol. 2004;75(1):16-22. https://pubmed.ncbi.nlm.nih.gov/15025213/
  3. Labriola A, Needleman I, Moles DR. Systematic review of the effect of smoking on nonsurgical periodontal therapy. Periodontol 2000. 2005;37:124-37. https://pubmed.ncbi.nlm.nih.gov/15655029/
  4. Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol. 2011;7(12):738-48. https://pubmed.ncbi.nlm.nih.gov/21709707/
  5. Graves DT, Ding Z, Yang Y. The impact of diabetes on periodontal diseases. Periodontol 2000. 2020;82(1):214-24. https://pubmed.ncbi.nlm.nih.gov/31850631/
  6. Löe H, Ånerud Å, Boysen H, Morrison E. Natural history of periodontal disease in man. Rapid, moderate and no loss of attachment in Sri Lankan labourers 14 to 46 years of age. J Clin Periodontol. 1986;13(5):431-45. https://pubmed.ncbi.nlm.nih.gov/3487557/

14. 전신 파급 — PISA, HbA1c, 내피 기능

PISA 계산식, IL6S → CRP → INSR → HBA1C 사슬, 그리고 집중 치료 24시간 후 FMD가 일시적으로 악화한 뒤 6개월에 개선되는 비단조 거동의 근거.

  1. Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A. Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol. 2008;35(8):668-73. https://pubmed.ncbi.nlm.nih.gov/18564145/
  2. Tonetti MS, D'Aiuto F, Nibali L, et al. Treatment of periodontitis and endothelial function. N Engl J Med. 2007;356(9):911-20. https://pubmed.ncbi.nlm.nih.gov/17329698/
  3. D'Aiuto F, Parkar M, Andreou G, et al. Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res. 2004;83(2):156-60. https://pubmed.ncbi.nlm.nih.gov/14742655/
  4. Simpson TC, Clarkson JE, Worthington HV, et al. Treatment of periodontitis for glycaemic control in people with diabetes mellitus. Cochrane Database Syst Rev. 2022;4(4):CD004714. https://pubmed.ncbi.nlm.nih.gov/35420698/
  5. Engebretson SP, Hyman LG, Michalowicz BS, et al. The effect of nonsurgical periodontal therapy on hemoglobin A1c in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial (DPTT). JAMA. 2013;310(23):2523-32. https://pubmed.ncbi.nlm.nih.gov/24346989/
  6. Sanz M, Marco del Castillo A, Jepsen S, et al. Periodontitis and cardiovascular diseases: consensus report. J Clin Periodontol. 2020;47(3):268-88. https://pubmed.ncbi.nlm.nih.gov/32011025/
  7. Michalowicz BS, Hodges JS, DiAngelis AJ, et al. Treatment of periodontal disease and the risk of preterm birth. N Engl J Med. 2006;355(18):1885-94. https://pubmed.ncbi.nlm.nih.gov/17079762/
  8. Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333. https://pubmed.ncbi.nlm.nih.gov/30746447/

15. 분류·역학·유지치료

Staging 출력, 유지치료(SPT)의 재발 방지 구조, H0_TOOTH 위험함수의 근거.

  1. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Clin Periodontol. 2018;45 Suppl 20:S149-61. https://pubmed.ncbi.nlm.nih.gov/29926495/
  2. Papapanou PN, Sanz M, Buduneli N, et al. Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop. J Clin Periodontol. 2018;45 Suppl 20:S162-70. https://pubmed.ncbi.nlm.nih.gov/29926490/
  3. Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res. 2014;93(11):1045-53. https://pubmed.ncbi.nlm.nih.gov/25261053/
  4. Axelsson P, Nyström B, Lindhe J. The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance. J Clin Periodontol. 2004;31(9):749-57. https://pubmed.ncbi.nlm.nih.gov/15312097/
  5. Chambrone L, Chambrone D, Lima LA, Chambrone LA. Predictors of tooth loss during long-term periodontal maintenance: a systematic review of observational studies. J Clin Periodontol. 2010;37(7):675-84. https://pubmed.ncbi.nlm.nih.gov/20528960/
  6. Lang NP, Adler R, Joss A, Nyman S. Absence of bleeding on probing. An indicator of periodontal stability. J Clin Periodontol. 1990;17(10):714-21. https://pubmed.ncbi.nlm.nih.gov/2262585/
  7. Socransky SS, Haffajee AD, Goodson JM, Lindhe J. New concepts of destructive periodontal disease. J Clin Periodontol. 1984;11(1):21-32. https://pubmed.ncbi.nlm.nih.gov/6584293/ (버스트 이론 — 본 모델의 부위 단위 쌍안정성 예측과 직접 대응하는 문헌)

16. 조직 재생

REGD 구획과 REGEN_FILL(재생만이 골소실을 되돌리는 유일한 경로)의 근거.

  1. Nyman S, Lindhe J, Karring T, Rylander H. New attachment following surgical treatment of human periodontal disease. J Clin Periodontol. 1982;9(4):290-6. https://pubmed.ncbi.nlm.nih.gov/6964676/
  2. Heijl L, Heden G, Svärdström G, Ostgren A. Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects. J Clin Periodontol. 1997;24(9 Pt 2):705-14. https://pubmed.ncbi.nlm.nih.gov/9310876/
  3. Nevins M, Giannobile WV, McGuire MK, et al. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol. 2005;76(12):2205-15. https://pubmed.ncbi.nlm.nih.gov/16332231/

17. QSP 방법론

  1. Ribba B, Grimm HP, Agoram B, et al. Methodologies for quantitative systems pharmacology (QSP) models: design and estimation. CPT Pharmacometrics Syst Pharmacol. 2017;6(8):496-8. https://pubmed.ncbi.nlm.nih.gov/28571119/
  2. Baron KT, Gastonguay MR. Simulation from ODE-based population PK/PD and systems pharmacology models in R with mrgsolve. J Pharmacokinet Pharmacodyn. 2015;42:S84-5. https://mrgsolve.org/
  3. Cheng Y, Thalhauser CJ, Smithline S, et al. QSP toolbox: computational implementation of integrated workflow components for deploying multi-scale mechanistic models. AAPS J. 2017;19(4):1002-16. https://pubmed.ncbi.nlm.nih.gov/28540623/

모델 보정에 직접 사용한 정량 목표 (Quantitative calibration targets)

아래 값들은 PDT_calibration_report()가 출력하는 목표치이며, 어느 것도 목적함수로 사용되지 않았습니다. 파라미터는 기전과 위 문헌의 독립적 측정값에서 설정했고, 임상 결과는 사후에 대조했습니다.

항목 문헌값 출처
SRP, 1-3 mm 부위 PPD 변화 -0.03 mm Cobb 1996/2002 (46, 47)
SRP, 1-3 mm 부위 CAL 변화 -0.34 mm (소실) Cobb (46, 47)
SRP, 4-6 mm 부위 PPD 감소 1.29 mm Cobb (46, 47)
SRP, 4-6 mm 부위 CAL 획득 0.55 mm Cobb (46, 47)
SRP, ≥7 mm 부위 PPD 감소 2.16 mm Cobb (46, 47)
SRP, ≥7 mm 부위 CAL 획득 1.19 mm Cobb (46, 47)
임계 탐침 깊이, SRP 2.9 mm Lindhe 1982 (48)
임계 탐침 깊이, 수술 4.2 mm Lindhe 1982 (48)
결석 제거율 3.0 / 4.5 / 6.5 mm 83 / 61 / 32 % Waerhaug 1978 (43)
Amox+metro 추가 CAL 획득 (깊은 부위) 0.40-0.50 mm Feres 2012 (53)
SDD 독시사이클린 추가 CAL 획득 0.30-0.40 mm Caton 2000 (59)
SDD, GCF 콜라게나제 감소 60-70 % Golub 1998 (36)
국소 미노사이클린 추가 PPD 감소 0.25-0.30 mm Williams 2001 (57)
클로르헥시딘 함수 추가 PPD 감소 ~0.00 mm Herrera 2020 (56)
AMY-101 단독, 28일 치은염증 감소 46 % Hasturk 2021 (62)
미치료 치조골 소실 0.15-0.40 mm/년 Löe 1986 (72)
치주치료 후 HbA1c 감소 0.43 % Simpson 2022 (76)
치주치료 후 CRP 감소 0.4-0.9 mg/L D'Aiuto 2004 (75)
6개월 FMD 개선 +2.0 % Tonetti 2007 (74)
집중치료 24시간 후 FMD 일시적 악화 Tonetti 2007 (74)
PISA, 전반성 3기 치주염 1000-2000 mm² Nesse 2008 (73)
흡연자 PPD 감소 저하 -0.40 ~ -0.50 mm Labriola 2005 (69)
플라크 전선-골정 거리 1.0-2.0 mm Waerhaug 1979 (33)

면책 (Disclaimer)

본 모델은 교육 및 가설 생성 목적의 정성적·반정량적 QSP 모델입니다. 공개 문헌에 근거하되 독립적으로 검증되지 않았으며, 임상 의사결정이나 규제 제출에 직접 사용해서는 안 됩니다.