Biochemical markers of bone metabolism in gingival crevicular fluid during early orthodontic tooth movement

Objective:To evaluate the expression of an activator of nuclear factor-kappa (RANK), osteoprotegerin (OPG), osteopontin (OPN), and transforming growth factor ß1 (TGF-ß1) in gingival crevicular fluid (GCF) of teeth subjected to orthodontic forces.Materials and Methods:A randomized, pilot clinical trial including 10 healthy volunteers was conducted using a split-mouth design. Orthodontic elastic separators were placed between the second premolar and first molar, with the contralateral quadrant serving as a control. The GCF samples were collected from the tension and compression sites at baseline, 24 hours, and 7 days after the placement of separators. The GCF sample volumes were measured using a Periotron 8000, and total protein concentrations were determined. Levels of RANK, OPG, OPN, and TGF-ß1 were also analyzed using a multiplex enzyme-linked immunosorbent assay.Results:The control sites remained unchanged throughout the study. In contrast, the concentration of OPG significantly decreased at the compression site by 24 hours, and the amount and concentration of RANK differed significantly between the control, compression, and tension sites after 7 days. A significant increase in absolute TGF-ß1 levels was also detected at the compression site versus the control and tension sites after 7 days.Conclusion:Bone metabolism is affected by application of force to the teeth by elastic separators. Both increased expression of bone resorptive mediators (eg, RANK and TGF-ß1) and decreased expression of a bone-forming mediator (eg, OPG) on the compression side were detected.     

Biomarkers of alveolar bone resorption in gingival crevicular fluid: A systematic review

BackgroundPeriodontitis is a prevalent oral disease with bone loss being it’s hallmark. Clinical parameters used to measure periodontitis are retrospective and do not indicate active inflammation nor prognosis. GCF can be easily collected chairside and bone turnover biomarkers found in GCF can be evaluated to check for active inflammation and disease progression. This systematic review aims to evaluate the literature for association and predictive value of bone turnover biomarkers in GCF during periodontal disease.Materials and MethodsThis review was conducted and reported according to the PRISMA guidelines. The online databases Google Scholar and PubMed were used for data search. MeSH terms were used for PubMed search. All original studies from 1990 to 2017 conducted on human subjects in the English language were included in the review. Studies on non-human subjects, reviews and studies conducted in languages other than English were not considered. Reference lists of qualified articles were also searched.ResultsThe search generated 2300 results whose titles were screened and 1571 articles were retreived. 23 articles were accepted in the review and full texts were accessed. These included 1 randomized controlled trial, 12 cross-sectional studies, five pre-post interventional studies, 4 longitudinal and 1 in-vitro in-vivo experimental study. The studies were conducted on patients of both genders ranging from 10 to 81 years in age. A total of 37 biomarkers were evalueted in the studies included in this review. Majority of the studies reported interleukin-1β (IL-1β) while receptor activated nuclear factor-kappa B ligand (RANKL) and matrix metalloproteinase-8 (MMP-8) were the other frequently reported biomarkers. Most of the studies evaluated more than two biomarkers. ELISA was the most commonly used biochemical test used for detection.ConclusionA wide range of biomarkers have been established as indicators of alveolar bone resorption. Few of the biomarkers have also shown positive correlation with disease progression and outcome of periodontal therapies thus underscoring their predictive value in periodontal diagnosis and prognosis. Not one single biomarker has been reported to have a predictive advantage over another and a combination of two or more biomarkers along with clinical evaluation is recommended.     

Lactoferrin and other markers from gingival crevicular fluid and saliva before and after periodontal treatment

OBJECTIVES: The aim of the study was to verify (i) if crevicular fluid defence variables reflect the changes after surgical periodontal treatment and (ii) if they are in correspondence with changes of these variables in the unstimulated and stimulated whole saliva. MATERIAL AND METHODS: For 12 male and 13 female volunteers with chronic periodontitis lactoferrin concentration as well as the lysozyme and peroxidase activities were determined in crevicular fluid as well as in unstimulated and stimulated saliva before and 14 days after surgical periodontal treatment by a minimal invasive flap technique. RESULTS: The lactoferrin concentrations decreased significantly in the crevicular fluid eluting solution from 1.63 to 1.23 mg/l reflecting a decrease in the total amount collected, in unstimulated saliva from 10.54 to 8.96 mg/l, and in stimulated saliva from 9.00 to 7.11 mg/l after treatment. No significant change could be found for lysozyme. Peroxidase activity was significantly reduced from 269.06 to 186.15 U/l only in the crevicular fluid. CONCLUSION: The results of this study suggest that (i) the defence factor lactoferrin is suitable for monitoring of periodontal treatment results and (ii) changes of the lactoferrin concentration in crevicular fluid are related with significant changes in unstimulated and stimulated saliva.     

Effect of orthodontic forces on cytokine and receptor levels in gingival crevicular fluid: a systematic review

This systematic review aimed to generate evidence on role of potent markers of inflammation [cytokines, chemokines, their associated receptors and antagonists] following the application of orthodontic forces. Subsequent to registration with PROSPERO, literature search followed a predetermined search strategy to key databases along with hand search (HS). Seventy-seven articles from PubMed (P), 637 from Scopus (S), 51 from Embase (E), and 3 from hand search (HS) were identified. A total of 39 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for participant characteristics, study design, oral hygiene regimen, and gingival crevicular fluid (GCF) handling. Among these studies, biomarkers in the order of frequency were interleukin (IL)-1β (N = 21), tumor necrosis factor (TNF)-α (N = 10), IL-8,IL-6(N=8), receptor activator of nuclear factor kappa-B ligand (RANKL) (N = 7), monocyte chemoattractant protein (MCP)-1 (N = 3), IL-2 (N=4), IL-4, IL-10, RANTES (N = 2), IL-1, IL-5, IL-1α, IP-10, osteopontin (OPN) (N = 1) and receptors and their antagonists in the order of osteoprotegerin (OPG) (N = 8), IL-1RA (N = 5), and RANK (N = 1). Results revealed an immediate release of inflammatory bone-resorptive mediators, IL-1β and TNF-α, where IL-1β increased as early as 1 min to 1 h reaching peak at 24 h while TNF-α increased at 1 h or 1 day. This was accompanied by a fall in bone-protective mediator (OPG) levels at 1 h and 24 h after orthodontic force application. Continuous forces were accompanied by a decrease in mediator levels after attaining peak levels (most commonly at 24 h) while repeated activations in interrupted force upregulated their secretion. Significant correlations of IL-1β levels with pain intensity, rate of orthodontic tooth movement (OTM) and of activity index (AI) (IL-1β/IL-1RA) with velocity of tooth movement and growth status of individuals have also been deduced. A greater AI and RANKL/OPG ratio was seen in juveniles as compared to adults or non-growers that were associated with faster rate of OTM in juveniles. None of the studies addressed the effect of estrous cycle in female subjects. Lack of homogeneity in several parameters calls for a better controlled research on the biology of OTM.

Electronic supplementary material

The online version of this article (doi:10.1186/s40510-014-0065-6) contains supplementary material, which is available to authorized users.     

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review

Objectives

The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO.

Materials and methods

MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers.

Results

The majority of the eight studies included confirmed a positive association between GCF mediators, such as interleukin-1β, prostaglandin E₂, and tumor necrosis factor-alpha, and APO. Due to the heterogeneity and variability of the available studies, no meta-analysis could be performed.

Conclusions

A positive association between GCF inflammatory mediator levels and APO/PTB might be present but the results need to be considered with great caution because of the heterogeneity and variability among the studies. Further studies with an adequate number of patients allowing for an appropriate analysis are warranted to definitely confirm this association.

Clinical relevance

The present findings suggest that an association between GCF inflammatory mediator levels and APO might exist.     

楔状缺损与龈沟液流量和pH值的关系

目的研究龈沟液流量和pH值对楔状缺损发生的影响。方法选取43例楔状缺损患者,每例选择3颗楔状缺损患牙和3颗正常牙,分别检测龈沟液流量和pH值。经统计学分析,比较楔状缺损牙和正常牙的龈沟液流量和pH值。结果楔状缺损组的龈沟液量大于正常组（P〈0．05）,pH值小于正常组（P〈0．01）。结论龈沟液流量和酸性程度可能与楔状缺损的发生有关。     

釉基质蛋白治疗牙周骨内缺损的系统评价

目的:比较并评价釉基质蛋白治疗牙周病骨内缺损的临床效果是否优于单用屏障膜的引导组织再生术.方法:主要检索7个数据库,部分全文通过手工检索获得.收集1997-2008年公开发表的中、英文釉基质蛋白及引导组织再生术的随机对照试验,随访时间至少半年.最终11个研究纳入系统评价.利用Meta分析,综合筛选出11篇适用文献.进行综合分析的测量结果包括术后牙周袋探诊深度(PD)减少、附着水平(CAL)增加、牙龈退缩水平(REC)的变化.结果:Meta分析结果显示,3种临床测量指标的基线水平在2治疗组间具有可比性,≥6个月后,3项指标的临床效果在2治疗组间比较无统计学差异.结论:现有的证据支持在牙周袋探诊深度减少、附着水平增加、牙龈退缩3项指标方面,釉基质蛋白治疗牙周病骨内缺损可取得与引导组织再生术相似的临床效果.     

Changes in amount of gingival crevicular fluid after a single episode of periodontal treatment

A total of 51 periodontal sites from 6 adults with no systemic diseases or medication were selected for the study. All sites showed radiologic bone loss and pockets of 4 mm or more. Crevicular fluid (CF) was collected by inserting filter paper strips into periodontal pockets for 5 s and was measured by Periotron. Samples were collected before and 2, 5, 10, 20, and 40 days after a single episode of periodontal treatment (scaling, root planing and curettage). Plaque Index (PII), Papilla Bleeding Index (PBI) and pocket depth (PD) were measured before and 40 days after treatment. The amount of bone loss was estimated from orthopantomograms taken immediately before the trial. Two days after treatment an increase in the amount of CF was seen. After this the amount of CF decreased, reaching the pretreatment level on day 5 after treatment and a level clearly below pretreatment level on day 10 after treatment. Forty days after treatment a slight increase in the amount of CF was seen. The difference between pretreatment values and values at days 2, 10, 20, and 40 was highly significant. In pretreatment samples, positive correlations were found between the amount of CF and PD, PBI and bone loss and, in samples collected 40 days after treatment between CF and PD. CF measurements made before treatment were of no value in predicting the changes in clinical parameters after treatment.     

Systematic review of wound healing biomarkers in peri-implant crevicular fluid during osseointegration

ObjectiveTo quantify and characterize the role of biomarkers in peri-implant crevicular fluid (PICF) at each stage of healing during osseointegration.DesignThis systematic review was performed in accordance with PRISMA guidelines using several databases: MedLine (PubMed), Embase, ISI Web of Science, Scopus, and Cochrane Library. Medical subject headings and their indexers were used with no other limitations until December 2017. The dataset was extended with relevant papers from the reference lists of selected papers and from the gray literature. Data was summarized for study objectives, patient demographics, methods used to analyze PICF, biomarker concentrations, results and main findings. Methodologic quality of each included study was assessed using the checklist created by Downs and Black.ResultsElectronic search resulted in 1698 articles. After excluding the duplicates, reading titles, abstracts and reference list reviews 30 prospective studies with longitudinal follow-up were selected. In total, 52 different biomarkers were identified. The most studied cytokines were interleukin (IL)-1, IL-1β, tumor necrosis factor alpha (TNF-α), and nitric oxide (NO). The earliest PICF specimens were collected immediately after implantation, and the latest at 16 weeks prior to occlusal loading. 36 biomarkers were quantified during week 1, 49 between day 10 and week 6, and 49 between weeks 8 and 12. Only 5 articles received good quality ratings.ConclusionThe mechanism by which inflammatory and bone biomarkers are released during osseointegration has not yet been identified. However, some hypotheses based on immune-modulated reactions are being explored to investigate early and asymptomatic implant failures. Given the available clinical studies, it was not possible to further explore the performance of all biomarkers already analyzed and to extrapolate their results to propose a consultable data system based on release volume or concentration because of clinical study and data heterogeneity.     

The monitoring of gingival crevicular fluid volume during orthodontic treatment: a longitudinal randomized split-mouth study

This randomized split-mouth study was aimed at evaluating whether an orthodontic appliance per se or orthodontic tooth movement can induce detectable changes in gingival crevicular fluid (GCF) volume, and thus whether GCF volume is a predictable biomarker for tissue remodelling incident to orthodontic tooth movement. Materials and Methods: Sixteen healthy orthodontic patients (7 females and 9 males; mean age, 17.7 years; range, 13-27 years) with the need for extraction of the first upper premolars were enrolled. One randomly chosen maxillary canine was subjected to a distalizing force by a 0.017 × 0.025 inch titanium-molybdenum alloy archwire and considered as the test tooth (TT). The contralateral canine, which was not subjected to any force but was included in an orthodontic appliance, was used as a control (CT). GCF sampling was performed at both mesial and distal sites of the CTs and TTs at baseline, immediately before applying the orthodontic appliance, and after 1 hour, 24 hours, and 7, 14, and 21 days. A Periotron was used to measure the GCF volume. A modest but significant increase in the GCF volume over time was seen in both the CTs (mesial sites) and the TTs (both mesial and distal sites) with no differences between the experimental teeth. Subclinical tissue inflammation consequent to the placement of the orthodontic appliance might be responsible for these GCF volume changes. The GCF volume does not appear to be a reliable biomarker for tissue remodelling during orthodontic treatment.     

Enamel matrix derivative for periodontal tissue regeneration in treatment of intrabony defects: a Cochrane systematic review

We reviewed the literature on the efficacy of enamel matrix derivative (EMD) in comparison with open flap debridement, guided tissue regeneration (GTR), and bone grafting for the treatment of intrabony defects. We searched four major electronic databases for randomized controlled trials (RCTs) with at least one year of follow-up. Several journals were handsearched with no language restrictions. Outcome measures were: tooth loss, changes in probing attachment levels (PAL), pocket depths (PPD), gingival recessions (REC), marginal bone levels on intraoral radiographs, and postoperative infections. Screening of eligible RCTs, assessment of the methodological quality, and data extraction were conducted in duplicate. No difference in tooth loss was observed. A meta-analysis (eight trials) showed that EMD-treated sites displayed statistically significant PAL improvements (mean difference 1.3 mm) and PPD reduction (1 mm) when compared to flap surgery. When EMD was compared to GTR (six trials), GTR showed a statistically significant reduction of PPD (0.6 mm) and increase of REC (0.5 mm). No difference in postoperative infections was observed. No trials compared EMD with bone grafts alone. EMD is able to significantly improve PAL levels and PPD reduction when compared to flap surgery; however, there is no evidence that more teeth could be saved. There was no evidence of important differences between EMD and GTR.     

Biomaterials for promoting periodontal regeneration in human intrabony defects: a systematic review

Intrabony periodontal defects are a frequent complication of periodontitis and, if left untreated, may negatively affect long‐term tooth prognosis. The optimal outcome of treatment in intrabony defects is considered to be the absence of bleeding on probing, the presence of shallow pockets associated with periodontal regeneration (i.e. formation of new root cementum with functionally orientated inserting periodontal ligament fibers connected to new alveolar bone) and no soft‐tissue recession. A plethora of different surgical techniques, often including implantation of various types of bone graft and/or bone substitutes, root surface demineralization, guided tissue regeneration, growth and differentiation factors, enamel matrix proteins or various combinations thereof, have been employed to achieve periodontal regeneration. Despite positive observations in animal models and successful outcomes reported for many of the available regenerative techniques and materials in patients, including histologic reports, robust information on the degree to which reported clinical improvements reflect true periodontal regeneration does not exist. Thus, the aim of this review was to summarize, in a systematic manner, the available histologic evidence on the effect of reconstructive periodontal surgery using various types of biomaterials to enhance periodontal wound healing/regeneration in human intrabony defects. In addition, the inherent problems associated with performing human histologic studies and in interpreting the results, as well as certain ethical considerations, are discussed. The results of the present systematic review indicate that periodontal regeneration in human intrabony defects can be achieved to a variable extent using a range of methods and materials. Periodontal regeneration has been observed following the use of a variety of bone grafts and substitutes, guided tissue regeneration, biological factors and combinations thereof. Combination approaches appear to provide the best outcomes, whilst implantation of alloplastic material alone demonstrated limited, to no, periodontal regeneration.     

Aspartate aminotransferase levels in gingival crevicular fluid before and after initial periodontal treatment

The present study investigates the presence of the enzyme aspartate aminotransferase (AST) in the gingival crevicular fluid (GCF) of untreated periodontal patients and determines the alterations in enzyme activity after the initial phase of periodontal treatment. From 12 patients suffering from advanced periodontitis, 54 pockets exhibiting severe attachment loss and depth > 4 mm were selected. Measurements of pocket depth (PD), attachment level (AL) and bleeding upon probing (BOP) were undertaken. For the GCF collection, sterile strips were gently placed at the previously isolated gingival crevice for 30 seconds and afterwards the GCF volume was determined with a Periotron 6000. The AST measurements were based on the establishment absorbency coefficient of NADH. The rate of decrease in the concentration of NADH is directly proportional to the AST activity in the sample. Four weeks after completion of the initial treatment, the patients were re-examined and the same clinical and laboratory measurements were performed. The parameters obtained were statistically analysed. The clinical parameters showed a statistically significant improvement, while the laboratory data expressed a statistically significant decrease of GCF volume as expected. Further, the sites were divided in two groups--pathological (pi) and physiological (phi)--according to Persson and Page (1991). After treatment a marked improvement concerning these values was noticed and it was noteworthy that these alterations occured regardless of initial AST presence.     

Collagen III aminoterminal propeptide in gingival crevicular fluid before and after periodontal treatment

The amount of procollagen III aminoterminal propeptide (PIIINP) in crevicular fluid (CF) was measured from three periodontitis patients before treatment (scaling, root planing, and curettage) and 2, 5, 10, 20, and 40 days after treatment. CF was collected by placing two paper strips in each pocket for 5 s, after which the amount of fluid was measured. Control samples were collected from three subjects with minimal gingival inflammation. PIIINP was extracted into saline solution and determined by a radioimmunological method. Plaque Index, Papilla Bleeding Index, and pocket depth were recorded before and 40 days after treatment. Forty days after treatment clinical parameters indicated healing. The CF PIIINP mean concentration was 162 μg/1 (range 0–430) in the pretreatment samples. Ten days after treatment, PIIINP mean concentration was 1400 μg/1 (range 1000–9000). After this, the concentration gradually decreased, reaching the pretreatment level 40 days after treatment. Most of the control samples showed undetectable amounts of PIIINP. It was suggested that elevated PIIINP concentrations in CF after periodontal treatment reflected increased type III collagen synthesis in gingiva. PIIINP concentrations before treatment reflected the rate of type III collagen turnover in inflamed periodontal tissues. It was further suggested that CF PIIINP has clinical value as an indicator of the healing process of inflamed gingiva.     

Changes in amount of gingival crevicular fluid after a single episode of periodontal treatment.

A total of 51 periodontal sites from 6 adults with no systemic diseases or medication were selected for the study. All sites showed radiologic bone loss and pockets of 4 mm or more. Crevicular fluid (CF) was collected by inserting filter paper strips into periodontal pockets for 5 s and was measured by Periotron. Samples were collected before and 2, 5, 10, 20, and 40 days after a single episode of periodontal treatment (scaling, root planing and curettage). Plaque Index (P1I), Papilla Bleeding Index (PBI) and pocket depth (PD) were measured before and 40 days after treatment. The amount of bone loss was estimated from orthopantomograms taken immediately before the trial. Two days after treatment an increase in the amount of CF was seen. After this the amount of CF decreased, reaching the pretreatment level on day 5 after treatment and a level clearly below pretreatment level on day 10 after treatment. Forty days after treatment a slight increase in the amount of CF was seen. The difference between pretreatment values and values at days 2, 10, 20, and 40 was highly significant. In pretreatment samples, positive correlations were found between the amount of CF and PD, PBI and bone loss and, in samples collected 40 days after treatment between CF and PD. CF measurements made before treatment were of no value in predicting the changes in clinical parameters after treatment.     

Changes in gingival crevicular fluid matrix metalloproteinase-8 levels during periodontal treatment and maintenance

OBJECTIVES: The aim of this study was to investigate the effect of scaling and root planing (SRP) and the maintenance phase of treatment on the gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels. MATERIALS AND METHODS: Clinical measurements and GCF samples were taken from four sites in 20 adult periodontitis patients before and after SRP and during a 3-month maintenance phase of treatment. MMP-8 levels were measured from GCF samples by time-resolved immunofluorometric assay (IFMA) with monoclonal antibodies. RESULTS: SRP improved the clinical indices as would be predicted, 6.1 mm (SD = 1.4) at baseline compared with 4.3 mm (SD = 1.6) post-treatment (P < 0.001). Attachment level (AL) reduced but not significantly between these two visits 13.4 mm (SD = 2.4) compared with 12.8 mm (SD = 2.4) (P < 0.08) post therapy. GCF MMP-8 levels reduced after initial treatment from 33.8 micro g/30 s sample to 23.5 micro g/30 s, which just failed to reach statistical significance (P = 0.07). However, when MMP-8 levels were expressed as a concentration, the differences following initial therapy were significant (54.1 ng/ micro L at baseline compared with 34.2 ng/micro L post treatment; P < 0.005). The difference, however, between the baseline MMP-8 levels (33.8 ng/30 s) and the final visit (16 ng/30 s) following maintenance was markedly significant (P < 0.001) for both absolute amounts and on a concentration basis. CONCLUSION: In conclusion, clinical improvement following SRP was associated with significant reductions in MMP-8 levels. The GCF concentration of MMP-8 decreased after initial therapy but reduced even more dramatically (approximately 50%) following a 3-month period of maintenance (P < 0.001).     

Collagen III aminoterminal propeptide in gingival crevicular fluid before and after periodontal treatment.

The amount of procollagen III aminoterminal propeptide (PIIINP) in crevicular fluid (CF) was measured from three periodontitis patients before treatment (scaling, root planing, and curettage) and 2, 5, 10, 20, and 40 days after treatment. CF was collected by placing two paper strips in each pocket for 5 s, after which the amount of fluid was measured. Control samples were collected from three subjects with minimal gingival inflammation. PIIINP was extracted into saline solution and determined by a radioimmunological method. Plaque Index, Papilla Bleeding Index, and pocket depth were recorded before and 40 days after treatment. Forty days after treatment clinical parameters indicated healing. The CF PIIINP mean concentration was 162 micrograms/l (range 0-430) in the pretreatment samples. Ten days after treatment, PIIINP mean concentration was 1400 micrograms/l (range 1000-9000). After this, the concentration gradually decreased, reaching the pretreatment level 40 days after treatment. Most of the control samples showed undetectable amounts of PIIINP. It was suggested that elevated PIIINP concentrations in CF after periodontal treatment reflected increased type III collagen synthesis in gingiva. PIIINP concentrations before treatment reflected the rate of type III collagen turnover in inflamed periodontal tissues. It was further suggested that CF PIIINP has clinical value as an indicator of the healing process of inflamed gingiva.     

Collagen I carboxyterminal propeptide in human gingival crevicular fluid before and after periodontal treatment

The amount of procollagen I carboxyterminal propeptide (PICP) in crevicular fluid (CF) was measured in three periodontitis patients. Samples were collected from 29 sites before treatment (scaling, root planing, and curettage) and 2, 5, 10, 20, and 40 days after treatment, by placing two paper strips in periodontal pockets for 5 s. The amount of fluid in strips was measured by the Periotron device. Control samples were collected from subjects with minimal gingival inflammation. PICP was extracted into saline solution and determined by a radioimmunologic method. Plaque index, papilla bleeding index, and pocket depth were recorded before and 40 days after treatment. The CF PICP mean concentration was 4.2 mg/1 in the pretreatment samples. Five days after treatment a statistically significant increase in PICP concentration was seen in all subjects. The peak appeared on days 5 or 10 in 27 sites. The mean peak PICP concentrations of the subjects were 5-10 times higher than the pretreatment values. Twenty days after treatment, mean PICP concentration decreased to pretreatment level. PICP concentrations did not correlate with the clinical parameters. In control samples PICP amounts were below the detection limit. CF PICP is a new marker of type 1 collagen metabolism in periodontal tissues. It was concluded that elevated PICP concentrations in CF after periodontal treatment reflected increased type I collagen synthesis in periodontal tissues and that the peak in type I collagen synthesis takes place 5-10 days after treatment.