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 ...