C‐Telopeptide Pyridinoline Cross‐Links: Sensitive Indicators of Periodontal Tissue Destruction

Abstract

C-telopeptides and related pyridinoline cross-links of bone Type I collagen are sensitive markers of bone resorption in osteolytic diseases such as osteoporosis and osteoarthritis. We have studied the release of C-telopeptide pyridinoline crosslinks of Type I collagen as measures of bone destruction in periodontal disease. Studies in preclinical animal models and humans have demonstrated the relationship between radiographic bone loss and crevicular fluid C-telopeptide levels. We have recently found that C-telopeptide levels correlate strongly with microbial pathogens associated with periodontitis and around endosseous dental implants. Host-modulation of bone-related collagen breakdown has been shown by studies in humans demonstrating that MMP inhibition blocks tissue destruction and release of C-telopeptides in patients with active periodontal disease.Periodontal disease is initiated by microbial pathogens that elicit a host immune response with subsequent tissue destruction of the periodontal structures. 1 Patients afflicted with periodontitis experience breakdown of alveolar bone, periodontal ligament, and tooth root cementum. Uncontrolled periodontal tissue destruction eventually leads to tooth loss. A challenge in periodontology is the accurate and early assessment of tissue breakdown in patients with periodontal disease. Current methods of disease detection lack diagnostic sensitivity and specificity. Periodontal diagnostic procedures address several important functions, which include: screening; diagnosis of specific periodontal diseases; identification of sites or subjects at increased risk of experiencing progression of periodontal destruction; treatment planning; and monitoring of therapy. 2 This paper focuses on the ability of the class of molecules known as the pyridinoline crosslinks to identify tooth sites or subjects at an increased risk of experiencing periodontal tissue destruction. Research will be reviewed in preclinical and clinical investigations that illustrate the relationship among pyridinoline cross-links, periodontal pathogens, and alveolar bone loss. The paper concludes with recent developments in the inhibition of periodontal tissue destruction by matrix metalloproteinase (MMP) inhibitors such as doxycycline. PYRIDINOLINE CROSS-LINKS:BIOCHEMISTRY AND CLINICAL CORRELATIONSPyridinoline cross-links have emerged as very promising biomarkers of bone resorption in an array of osteolytic diseases. Pyridinoline (hydroxylysl pyridinoline or Pyr) and deoxypyridinoline (lysyl pyridinoline or Dpy), N-telopeptides, and C-telopeptides have been the best studied members of this class of collagen-degradative molecules. links formed by lysyl oxidase on lysine and hydroxylysine residues in the N-and C-terminal regions of collagen chains. This process results in the formation of divalent collagen crosslinks that by further condensation yield trivalent Pyr and Dpy.Osteoclastic bone resorption initiates the release of cross-linked immunoreactive telopeptides Pyr and Dpy. Urinary levels of Pyr and ...

A new method of monitoring osteomyelitis

“…Quantification of the concentrations of HP and, in particular, LP has been shown to be valuable in revealing the presence and/or extent of metastatic disease to bone in patients with oral cancers, multiple myeloma or carcinomas of the breast, lung, prostate, kidney, throat or digestive tract 31 . In accordance with other authors, it has previously been demonstrated that local alveolar bone resorption in cases of advanced periodontitis leads to elevated concentrations of HP and LP in crevicular fluid 14,21 . On this basis, it was hypothesized that infection of the mandibular bone may lead to increased urinary concentrations of HP and LP.…”

Plasma Levels of C-Telopeptide Pyridinoline Cross-Links of Type I Collagen and Osteocalcin in Chronic Periodontitis

“…Increased levels of ICTP have been observed in the GCF of periodontitis patients [8,14]. Lappin et al [2] reported higher median plasma concentrations of ICTP in periodontitis groups than the healthy subjects where the differences failed to reach statistical significance.…”

“…Studies assessing the role of ICTP levels in gingival crevicular fluid (GCF) or peri-implant crevicular fluid as a diagnostic marker of periodontal disease activity have reported promising results so far [6,7]. ICTP has been suggested to predict future bone loss, to correlate with clinical parameters, and also to reduce following periodontal therapy [8]. Increased circulating amounts of ICTP indicate an increase in osteoclast activity.…”

Recent Advances in Salivary Proteomics, Genomics and Transcriptomics: A Reliable Tool in Periodontal diagnosis – A Review

“…Various studies have investigated the role of pyridinoline cross-links to detect bone resorption in periodontitis and periimplantitis as well as in response to periodontal therapy (29,30). ICTP has been shown to be a hopeful predictor of both future alveolar bone and attachment loss.…”