title: Crevicular fluid osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as markers of rapid bone turnover in periodontitis. A pilot study in beagle dogs.
abstract: The objective of this study was to correlate the levels of 2 putative markers of bone metabolism, namely osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), to the progression of experimental alveolar bone loss in the beagle dog. 36 control sites and 36 experimental sites in 2 beagle dogs were assessed longitudinally at 2-week intervals for gingival crevicular fluid (GCF) osteocalcin and ICTP levels during a 6-month observation period. Analysis of osteocalcin and ICTP in GCF was performed by RIA. During the study, bone-seeking radiopharmaceutical uptake (BSRU) of 99mTc-MDP was assessed monthly; standardized radiographs were taken at 2-week intervals. The results showed osteocalcin and ICTP levels in GCF increased significantly (p < 0.05) by 2 weeks following initiation of disease. This increase preceded significant increases in BSRU by 2 weeks and radiographic evidence of bone loss by 4 weeks. BSRU was significantly elevated (p < 0.05) at experimental sites as compared to controls at 4 and 8 weeks post-disease initiation. Osteocalcin in GCF peaked 8 and 10 weeks after ligature placement in experimental sites at levels nearly 10-fold greater than contralateral paired control sites. ICTP levels in GCF remained elevated throughout the entire disease progression phase. Following the removal of ligatures, both GCF osteocalcin and ICTP levels dropped precipitously approaching control values. Osteocalcin revealed overall a positive predictive value (PPV) and negative predictive value (NPV) for future bone loss during disease progression of 0.87 and 0.34, respectively, while ICTP showed both high PPV and NPV of 0.87 and 0.91 respectively. Results from this study in the dog model indicate that osteocalcin and especially ICTP relate to indices of active periodontal bony destruction and suggest that these molecules may serve as predictive markers for future alveolar bone loss.
authors.affiliation: Department of Periodontology, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: W V
authors.initials: WV
authors.lastname: Giannobile
authors.forename: S E
authors.initials: SE
authors.lastname: Lynch
authors.forename: R G
authors.initials: RG
authors.lastname: Denmark
authors.forename: D W
authors.initials: DW
authors.lastname: Paquette
authors.forename: J P
authors.initials: JP
authors.lastname: Fiorellini
authors.forename: R C
authors.initials: RC
authors.lastname: Williams
mesh_terms: D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000378:metabolism; D000539:Alveolar Process / Q000000981:diagnostic imaging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D003094:Collagen / Q000032:analysis*; D024042:Collagen Type I; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D005544:Forecasting; D005883:Gingival Crevicular Fluid / Q000737:chemistry*; D008137:Longitudinal Studies; D008297:Male; D015675:Osteocalcin / Q000032:analysis*; D010455:Peptides / Q000032:analysis*; D010518:Periodontitis / Q000000981:diagnostic imaging / Q000378:metabolism*; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011859:Radiography; D012680:Sensitivity and Specificity; D013669:Technetium Tc 99m Medronate / Q000493:pharmacokinetics
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen; D013669:Technetium Tc 99m Medronate