International Journal of Dental Research &

Development (IJDRD)
ISSN(P): 2250-2386; ISSN(E): 2321-0117
Vol. 6, Issue 1, Apr 2016, 1- 10
TJPRC Pvt. Ltd.

C-TELOPEPTIDE AS DIAGNOSTIC MARKER FOR

ACTIVE PERIODONTAL DESTRUCTION- A REVIEW
P.R.GANESH
Assistant Professor, Department of Periodontics, Government Dental College, Chennai, Tamil Nadu, India
ABSTRACT
As classical periodontal disease manifests itself by alternating between periods of active tissue destruction and
quiescent intervals it becomes essential to differentiate the two to formulate an adequate treatment plan at the earliest
possible time. As current methods of peridontal diagnosis based on clinical parameters like probing depth and clinical
attachment loss and radiological diagnostic methods prove inadequate for accurate diagnosis of active destructon areas,
newer modalities which involve using biomarkers from oral fluids like saliva and gingival crevicualr fluid are being
advocated to supplement clinical diagmostics. As the predominant connective tissue component of periodontal tissues is
collagen, the use of collagen degradation products like C-Telopeptides as disease specific biomarkers to identify collagen
degradation and bone turnover is gaining current relevance. Hence use of C-TP as a proteome biomarker to identify
active periodontal and peri-implant bone destruction from latent disease sites may be useful for predicting disease
progression and earlier intervention.
KEYWORDS: C-Telopeptide, Oral Biomarkers, Proteome Diagnostics, Periodontal Disease, Peri-Implantitis, Collagen
Degradation Products.

Received: Mar 02, 2016; Accepted: Mar 10, 2016; Published: Mar 31, 2016; Paper Id.: IJDRDAPR20161

INTRODUCTION

presentation of inflammation of the marginal and inter-dental gingiva. After its progression from gingivitis, the
disease manifests as loss of connective tissue structures- specifically the loss of collagen fibers and its concomitant
loss of attachment to the root surface, followed by apical migration of the pocket epithelium, formation of deep
periodontal pockets and progressive resorption of alveolar bone leading to increased tooth mobility and finally tooth
loss as an endpoint of the disease progression

[1]

. Traditionally diagnosis of periodontal disease is made using

Original Article

Periodontitis is a chronic, inflammatory disease of the supporting tissues of the teeth with an initial

clinical parameters like measurement of probing depth, measurement of clinical attachment loss and the presence or
absence of bleeding on probing to indicate periodontal disease sites. But the traditional clinical criteria used to
identify periodontal disease are often insufficient for determining the presence of active disease sites, for monitoring
quantitatively the response to periodontal therapy or for measuring the degree of susceptibility to future disease
progression in healed or quiescent sites.
Hence the need for employing alternative diagnostic methods like microbiological, serological and
radiographical to supplement clinical diagnosis becomes essential. Although serological biomarkers have been used
with varying degree of success in diagnosing periodontal disease the justification of causality with remote origin of
bone remodeling molecules does indicate a questionable pause in the widespread adaptation of serological markers

www.tjprc.org

editor@tjprc.org

P.R.Ganesh

for diagnosis of periodontitis.

Hence the on going process of developing biomarkers for diagnosis from areas closer to the periodontal disease
sites has necessitated taking a closer look at oral biofluids which are at close proximity to the actual disease sites and can
accurately reflect the changes taking place in the periodontal tissues.
One of the most exciting new developments in periodontal disease diagnosis is the use of biomarkers from oral
fluids like saliva and gcf to obtain clinically relevant information and to supplement and reinforce clinical diagnosis.[2].
These biomarkers have become diagnostically important not only because they are specific for the unique pathological
aspects of periodontal disease but also because the qualitative changes in the composition of these periodontitis specific
bio-markers has a practical diagnostic value in identifying patients with enhanced disease susceptibility, in identifying sites
with active continuing disease, in predicting sites that will have active disease in the near future and serving as surrogate
end point for monitoring the efficacy of any therapeutic intervention undertaken to arrest the disease process and
regenerate the lost tissues.[3] .
Regardless of whether they are obtained from saliva or GCF these biochemical markers of bone remodulation
processes are used to analyze changes in the organic bone matrix of the alveolar bone. The organic matrix of the
periodontal tissues consists of predominantly collagen (approximately 95%) and non-collagenous proteins, the catabolic
products of the organic bone components, enzymes of osteoblasts and osteoclasts like alkaline phosphatase, bone
sialoprotein, osteopontin etc, as the calcium and phosphate levels in biologic fluids are the most reliable markers of active
skeletal bone tissue remodulation. Hence the biochemical analyses of oral biofluids enable the determining of the rates of
bone tissue reorganization and the current activity of osteosynthesis and osteoresorption processes with a fair degree of
certainty.[4]
As collagen is the predominant connective tissue component of periodontal tissues a class of degradation
molecules known as pyridinoline, deoxypyridinoline, N-telopeptides, and C-telopeptides which are released systemically
during degradation of collagen matrix and bone resorption due to post-translational modification of collagen have emerged
as valuable proteome markers for bone turnover and are very specific for periodontal disease.

[5,6]

Presence or absence of

these markers accurately differentiates the active periodontal or peri-implant bone destruction from latent periodontal
disease [7]
Palys et al. related pyridinoline cross-linked carboxy terminal telopeptide of type I collagen (ICTP) levels to the
subgingival microflora of various periodontal disease states in GCF and found ICTP levels differed significantly between
health, gingivitis, and periodontitis subjects, and also related modestly to several clinical disease parameters in the
progression of periodontal disease

[8]

. Furthermore the presence of depleted levels of ICTP subsequent to periodontal

therapy imply that it is a good indicator of future alveolar bone and clinical attachment loss and can hence be used for risk
assessment and prognosis of disease progression.[9]. Hence along with the development of newer therapeutic modalities to
achieve regeneration of

hitherto lost periodontal tissues which is the

gold standard of treatment endpoint, newer

modalities for diagnosis too are being actively developed as there is an increasing need for research and development of
original diagnostic tools that will expectantly demonstrate increased sensitivity and specificity enabling us to make correct
therapeutic and prognostic decisions.[10]

Impact Factor (JCC): 1.9876

Index Copernicus Value (ICV): 6.1

C-Telopeptide as Diagnostic Marker for Active Periodontal Destruction- A Review

Specific Diagnostic Tests

An oral diagnostic tool, in general, should provide pertinent information for differential diagnosis, localization of
disease and severity of infection at a specific site level intraorally. The current paradigm of the pathogenesis of periodontal
disease shows a wide variation in the magnitude of the inflammatory response around different teeth and in different sites
suggesting periods of rapid progression interspersed with periods of quiescence. Factors such as smoking, diabetes,
psychological stress, reduced serum antibodies, or biochemical mediators of inflammation are also linked to disease
progression rates.
Hence, the severity and progression of periodontal disease has been linked to a combination of genetic, host
response, microbial challenge and local environmental factors making it a multifactorial disease and consequently difficult
to diagnose with single specific diagnostic methodologies.[11] . But the diagnosis of periodontal diseases and treatment
outcome assessments are currently based predominantly on clinical signs such as tissue color and contour, the presence or
absence of bleeding on probing, gingival recession, probing pocket depths, attachment levels, suppuration, and tooth
mobility as surrogate markers of the active disease progression taking place at site and tooth level.[12] Even radiographs are
only used as an additional tool to visualize the previous loss of periodontal tissue, by helping to determine the amount of
bone loss around the affected teeth and hence cannot be characterized as a defintive diagnostic tool of active periodontal
tissue destruction.[13] As all these methods are only useful to assess the past disease activity they can be relied upon only to
a certain level of significance.
A definitive and reliable diagnostic method essential to accurately assess the active disease status of specific sites
and also for monitoring the site response to periodontal therapy is currently not available. Thus the development of more
sensitive and specific tests whether clinical, biochemical or radiographical would help us to determine whether a patient
has active periodontitis and what sort of attachment loss might be expected if the patient were not treated and the chronic
inflammatory burden of the periodontal tissues continued unresolved.
Biomarker Tests
A biomarker, or biological marker, is in general a substance used as an indicator of a biological state in oral
diagnostics. Biomarkers, whether produced by normal healthy individuals or by individuals affected by specific systemic
diseases, are tell-tale molecules that could be used to monitor health status, disease onset, treatment response and outcome.
Disease specific informative biomarkers can further serve as early sentinels of disease and thus have been considered as
the most promising alternative to the currently available screening tests for periodontal diseases. As of now it has been a
great challenge to determine specific biomarkers for screening, prognosis and evaluating the disease activity and also the
efficacy of therapy (diagnostic tests versus therapy tests) in periodontal diseases as an oral diagnostic tool, in general,
should provide pertinent information for differential diagnosis, localization of disease and severity of infection at a specific
site level.
Biomarkers of Periodontal Disease Fall into Three Categories:

Indicators of current disease activity;

Predictors of future disease progression;

Predictors of future disease initiation at currently healthy site

www.tjprc.org

editor@tjprc.org

P.R.Ganesh

The Periodontal disease biomarkers can either be Salivary Biomarkers or GCF biomarkers or markers present in
both oral fluids. Many different biomarkers associated with bone formation, resorption and turnover, such as alkaline
phosphatase, osteocalcin, osteonectin and collagen telopeptidases, have been evaluated in gingival crevicular fluid and
saliva.[3] These disease specific informative biomarkers can further serve as early sentinels of disease and thus have been
considered as the most promising alternative to the currently available screening tests for periodontal diseases. As of now it
has been a great challenge to determine specific biomarkers for screening, prognosis and evaluating the disease activity and
also the efficacy of therapy (diagnostic tests versus therapy tests) in periodontal diseases.
Bone Metabolism in Destructive Periodontal Disease
Bone, is characterized by two fundamental features, a high mechanical resistance due to its minerals and also
considerable elasticity due to its organic components. The alveolar bone of the jaws is in a constant state of flux with
continuous structural reshaping occurring through resorption and apposition simultaneously induced by the modification of
the forces directed at both a macro and micro level of the alveolus, so that they withstand efficiently the mechanical
stresses caused by both physiological and pathological biting forces. Hence the alveolar bone reshaping is controlled by a
complex series of local and systemic factors that regulate both the structural and the metabolic functions of bone. [14, 15]
Collagen is not only the most abundant protein in the human body and at the same time, it is the most important
one. Soft organs contain a relatively small amount of collagen, while the bone contains 23% from the dry mass. The main
function of collagen is to provide resistance and to maintain the structural integrity of the tissues. Collagen undergoes some
important metabolic synthesis and degradation processes in various conditions. The modifications in the metabolism of
collagen explain a series of metabolic mechanisms that occur in conditions as diverse as diabetes mellitus and osteoporosis.
[16]

Type I collagen comprises 90% of the organ matrix of the bone and it is the most abundant collagen in the bone
tissue. The degradation products of collagen are considered to be important markers of the bone turnover in several
osteolytic or bone metabolic diseases.[17] Several investigators have implicated bone specific pyridinoline cross-links as
markers of bone resorption in periodontitis [ 18] and peri-implantitis [19] .
Hence analysis of antigens related to collagen formation and degradation in bone can provide good and specific
estimates of both bone resorption and bone formation rates. A study by Erikesen et al measured serum levels of the
pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxyterminal propeptide of type I pro-collagen (PICP) as a marker of bone formation. [6] Serum levels of the two antigens were
correlated to histomorphometric indices of bone resorption and bone formation with high confidence.
Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the
evaluation of rates of bone remodeling.[6] A reliable increase in the serum levels of bone tissue resorption markers
(deoxypiridinolin and C-terminal telopeptide of type 1 collagen) and a decrease of markers reflecting bone formation
(osteocalcin, bone-specific alkaline phosphatase) was noted in patients with exacerbated generalized periodontitis as
compared with the control group by Mazur etal.[20]
Biochemical markers of bone turnover which provide an insight into the dynamic changes of the skeletal bones
can also be used as research tools to study the pathogenesis and treatment of bone diseases.[21] Research using bone
biomarkers has suggested their clinical use to monitor the effect of antiresorptive therapy [22], Collagen turnover [23] predict
Impact Factor (JCC): 1.9876

Index Copernicus Value (ICV): 6.1

C-Telopeptide as Diagnostic Marker for Active Periodontal Destruction- A Review

bone loss and fracture in osteoporosis

[24]

, predict complications of metastatic bone disease

progression of joint damage in rheumatoid arthritis

multiple myeloma

[25]

[23]

, and to identify the

and the extent of bone involvement in metastatic cancer and

[26, 27]

C-Telopeptide
C-TeloPeptide is a member of a family of pyridinoline cross-links which are specific for osseous and cartilaginous
tissues

[9]

. The pyridinoline cross-links include free pyridinoline, deoxypyridinoline, the C-terminal and N-terminal

telopeptide molecules. Hence, CTP represents one member of an important group of molecules which are highly associated
with bone resorptive diseases.
The Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (CTP) is derived from the
carboxyterminal telopeptide regions of type I collagen cross-linked via pyridinoline or deoxypyridinoline

[28]

Following

procollagen synthesis and its release into the maturing extracellular matrix, collagen fibrils undergo post-translational
modification resulting in cross-links between the telopeptide regions of type I collagen chains by lysyl oxidase. The ICTP
cross-link contains two carboxyterminal telopeptides of the 1 chain and one helical region from the 2 chain. These crosslinks are essential for providing mechanical stability to the maturing matrix and are specific to bone and cartilage and are
not found in soft tissues such as skin where the cross-link is initiated by histidine residues

[22]

. Elevated serum levels of

Type1 collagen have been shown to correlate with bone resorptive metabolic diseases such as primary hyperparathyroidism
and post-menopausal osteoporosis [6, 29].
The release of pyridinoline cross-links into urine or blood can be reversed by estrogen replacement or
bisphosphonate therapy which inhibit osteoclastic bone resorption

[24, 25]

When released from the extracellular matrix of

mineralized tissues such as alveolar bone, pyridinoline cross-links can be detected in the GCF by immunological methods.
Therefore, CTP may be a first generation pyridinoline cross-link detectable in GCF. Newer methods may involve the use
of deoxypyridinoline and other cross-links as immunodetection methods are optimized. Various studies have shown a
correlation between the level of the PICP and the bone resorption rate as propeptides share these properties with most of
the parameters of the metabolism of collagen [30].
Serum CTP values have been used as biochemical markers of bone formation and resorption. Variables that affect
CTP measurement include age, alcohol consumption, smoking, ovulation, gender, drugs (e.g., corticosteroids), disease
(e.g., diabetes), exercise, and circadian rhythms. [31,32] Overnight fasting is one of the most commonly used techniques to
minimize the variability of bone turnover markers as variation during fasting is 8.8%. [7] .
Talonpoika , Hmlinen eta1 in 1994 demonstrated a relationship between ICTP and inflammatory periodontal
disease

[18]

. The initiation of osteoclastic bone destruction and the corresponding elevation in deoxypyridinoline could be

detected within 3 days of disease induction by immunohistochemical staining of TRAP+ osteoclast-like cells. Therefore,
pyridinoline cross-links may be useful for predicting future bone loss in the periodontium. [9, 18]
C-Telopeptide In Saliva
Easily collected and containing local and systemic derived biomarkers of periodontal disease, oral fluids may
offer the basis for patient-specific diagnostic tests for periodontal disease. Secretions from the major salivary glands
(parotid, submandibular and sublingual), which have a large number of proteins and peptides, are responsible for
maintaining the integrity of the oral cavity. Also, because of its importance in oral biofilm formation and host defense,
www.tjprc.org

editor@tjprc.org

P.R.Ganesh

secreted saliva may have a significant role in the establishment and progression of periodontal disease.

[33]

Saliva (oral

fluid) is a mirror of the body. It could be used to monitor the general health and the onset of specific diseases. Informative
biomarkers from saliva can further serve as early sentinels of disease, and this has been considered as the most promising
alternative to classic environmental epidemiology. [34]
Saliva is simple, non-invasive, readily available and easily collected without specialized equipment or personnel.
For the past two decades, saliva has been increasingly evaluated as a diagnostic fluid for detecting breast cancer, oral
cancer, caries risk, salivary gland diseases, periodontitis and systemic disorders such as hepatitis C and the presence of
human immunodeficiency virus (HIV).
Various mediators of chronic inflammation and tissue estruction have been detected in whole saliva of patient
with oral diseases.Also, for some diagnostic purposes, salivary biomarkers proved more useful than serum analysis [33] . Creactive protein is a systemic marker released during the acute phase of an inflammatory response. C-reactive protein is
produced by the liver and is stimulated by circulating cytokines, such as tumor necrosis factor-a and interleukin-1, from
local and /or systemic inflammation such as periodontal inflammation. Circulating C-reactive protein may reach saliva via
gingival crevicular fluid or the salivary glands. High levels of C-reactive protein have been associated with chronic and
aggressive periodontal diseases and with other inflammatory biomarkers. Studies have demonstrated that periodontal
patients display elevated concentrations of serum C-reactive protein when compared with healthy individuals C-reactive
protein has recently been shown to be measurable in saliva from periodontal patients using a lab-on-a-chip method .[35]
Matrix metalloproteinases are host proteinases responsible for both tissue degradation and remodeling. During
progressive periodontal breakdown, gingival and periodontal ligament collagens are cleaved by host cell-derived interstitial
collagenases. MMP-8 is the most prevalent MMP found in diseased periodontal tissue and gingival crevicular fluid.
Elevated MMP-8 levels in active disease progression were observed in a longitudinal study of patients with gingivitis and
with nonprogressive and progressive periodontitis. Recently, the level of MMP-8 was demonstrated to be highly elevated
in saliva from patients with periodontal disease using a rapid point-of-care microfluidic device.[36]
Many different biomarkers associated with bone formation, resorption and turnover,such as alkaline Phosphatase,
osteocalcin,osteonectin and collagen telopeptidases,have been valuated in gingival crevicular fluid and saliva

[3]

. These

mediators are associated with local bone metabolism (in the case of periodontitis) as well as with systemic conditions such
as osteoporosis or metastatic bone cancers. Khashu H, Baiju CS, Bansal SR etal, in 2012 have reported that pyridinoline
cross-linked carboxyterminal telopeptide of type I collagen is a valuable diagnostic aid for periodontal disease due to the
ability of pyridinoline cross-links to detect bone resorption

[37]

. Furthermore, the levels of carboxyterminal telopeptide of

type I collagen were strongly correlated with clinical parameters and putative periodontal pathogens, and demonstrated
significant reductions after periodontal therapy.

[37]

Controlled human longitudinal trials are needed to establish fully the

role of salivary carboxyterminal telopeptide of type I collagen as a predictor of periodontal tissue destruction, disease
activity and response to therapy in periodontal patients. [33, 9]
C-Telopeptide in GCF
In recent years Gingival crevicular fluid (GCF), has gained great interest on possible diagnostic value in
periodontal disease. It contains a large number of proteins and peptides derived from inflamed host tissues ane hence the
analysis of the GCF components are used to isolate the disease status of individual sites and thus, identify potential

Impact Factor (JCC): 1.9876

Index Copernicus Value (ICV): 6.1

C-Telopeptide as Diagnostic Marker for Active Periodontal Destruction- A Review

biomarkers of periodontitis.

[38]

Gingival crevicular fluid is both a physiological fluid as well as an inflammatory exudate,

originating from the gingival plexus of blood vessels in the gingival corium, subjacent to the epithelium lining of the
entogingival space.
As gingival crevicular fluid traverses through inflamed periodontal tissues en route to the sulcus, biological
molecular markers are gathered from the surrounding areas and are subsequently eluted into whole saliva.
Gingival crevicular fluid (GCF) is a complex mixture of substances derived from serum, host inflammatory cells, structural
cells of the periodontium, and oral bacteria. [30] GCF originates from the vessels of the gingival plexus of blood vessels and
flows through the external basement membrane and the junctional epithelium to reach the gingival sulcus. GCF can be
isolated from healthy sulcus, although only in small amounts. In the healthy periodontium, GCF represents the transudate
of gingival tissue interstitial fluid produced by an osmotic gradient.
The products of the inflammatory response which occur during the disease process can be found in the GCF [10].
Monitoring of the presence of such components can be of potential value in evaluating periodontal disease status or
outcomes of periodontal therapy. Gingival crevicular fluid sampling methods have been shown to capture inflammatory
and connective tissue breakdown mediators accurately. To date, more than 90 different components in gingival crevicular
fluid have been evaluated for periodontal diagnosis. [38] Of the numerous constituents in gingival crevicular fluid, however,
the vast majority constitute soft-tissue inflammatory events, while only a few are regarded as specific biomarkers of
alveolar bone destruction. [3] The most promising gingival crevicular fluid markers of disease progression/connective tissue
destruction are probably host breakdown products (as opposed to the enzymes that break down host tissues). This is
especially true of markers that represent bone destruction and include chondroitin-4-sulfate, pyridinoline cross-links of the
carboxyterminal telopeptide of type I collagen, and RankL (receptor activator for NF-xB ligand). [39]
Given the specificity and sensitivity for bone resorption, pyridinoline cross-links, such as pyridinoline crosslinked carboxyterminal telopeptide of type I collagen represent a potentially valuable diagnostic aid for periodontal
disease. Several investigations

have explored the ability of pyridinoline cross-links to detect bone resorption in

periodontitis and peri-implantitis, as well as in response to eriodontal therapy.

[18, 19]

As the cross-linked telopeptides

resulting from posttranslational modification of collagen molecules cannot be reused during collagen synthesis they are
considered specific biomarkers for bone resorption.

[6]

Pyridinoline cross linked carboxyterminal telopeptide of

type1collagen (ICTP) is 12 to 20 Kd fragment of bone type1collagen released by digesting with trypsin or bacterial
collagenase. According to Palys et al in 1998, GCF ICTP levels were related to subgingival microflora of periodontal
diseases and hence GCF ICTP levels are a good predictor of future alveolar bone and attachment oss and are strongly
correlated with clinicalparameters and putative periodontal pathogen. [8]
Talonpoika JT, Hmlinen MM studied a total of 126 gingival crevicular fluid (GCF) samples from 20 adults
using paper strips and concluded that GCF ICTP reflects the local type I collagen degradation in periodontal tissues and
also gives information about the tissue destruction process beyond the reach of the clinical parameters.

[18]

. These

investigations have shown that ICTP correlated strongly with radiographic bone level and pocket depth and was
significantly higher at periodontitis sites compared to non-periodontitis sites [18]. Moreover, ICTP was highly sensitive and
specific for predicting future alveolar bone loss as measured by computer-assisted digitizing radiography.[34].

www.tjprc.org

editor@tjprc.org

P.R.Ganesh

CONCLUSIONS
Periodontal diagnosis and treatment plan are based on the assessment of probing depth, clinical attachment level,
plaque index, gingival index, bleeding on probing, suppuration, furcation involvement, mobility, and radiographic findings.
However, these clinical parameters are not sufficiently sensitive and specific to identify disease activity in individual sites
or to predict future attachment loss. Hence, attention is focused on the development of diagnostic tools that could screen
and differentiate the active inflamed sites and predict future tissue destruction.
It is noteworthy that in developing newer treatment strategies and diagnostic tests, it has been essential to become
more knowledgeable about the patho-physiological mechanisms underlying periodontitis. And that with this information
the physiological and patho-physiological continuum that connects tissues in the oral cavity to other remote organ systems
in both health and disease can also been defined and recognized with increasing clarity. This concept also presages a more
biological approach being taken by dentists regarding diagnosis and management of oral diseases. The periodontists of the
21st century will approach oral diseases using a more biological model of health, disease and disease management; an
approach more befitting physicians of the oral cavity.
While the future of periodontal disease diagnosis using oral fluid biomarkers looks promising, obstacles to these
approaches may appear in the clinical setting. Validation of novel periodontal diagnostics will need to be benchmarked
with existing gold standards of disease, such as alveolar bone levels and clinical attachment levels, in large patient
populations. Acceptance by clinicians is also necessary and may prove difficult if techincal feasability is complicated.
However if a demosntably more efficient periodontal therapy can be delivered, clinicians will be more likely to utilize the
new diagnostic approaches. Although challenges remain ahead, the use of biomarkers based oral fluid diagnostics appear
promising for future application to diagnose periodontal diseases and to prognosticate periodontal treatment outcomes.
REFERENCES
1.
2.

Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol 1996: 1: 821878.

Maupome G, Pretty IA, Hannigan E, et al. A closer look at diagnosis in clinical dental practice: part 4. Effectiveness of nonradiographic diagnostic procedures and devices in dental practice. J Can Dent Assoc 2004;70(7):4704.

3.

Kinney JS, Ramseier CA, Giannobile WV. Oral fluid-based biomarkers of alveolar bone loss in periodontitis. Ann N Y Acad
Sci 2007: 1098: 230251.

4.

Moseley R, Stewart JE, Stephens RJ, et al. Extracellular matrix metabolites as potential biomarkers of disease activity in
wound fluid: lessons learned from other inflammatory diseases? Br J Dermatol 2004;150(3):40113.

5.

Johnell O, Odn A, De Laet C, Garnero, Delmas PD, etal, Biochemical indices of bone turnover and the assessment of
fracture probability, Osteoporosis International, 2002 vol. 13, no. 7, pp. 523526.

6.

Eriksen EF, Charles P, Melsen F, Mosekilde L, etal : Serum markers of type I collagen formation and degradation in
metabolic bone disease: correlation with bone histomorphometry, Journal of Bone and Mineral Research, Vol. 8, no. 2, pp.
127132, 1993.

7.

Giannobile WV, Crevicular fluid biomarkers of oral bone loss, Current Opinion in Periodontology, 1997, vol. 4, pp. 1120.

8.

Palys MD, Haffajee AD, Socransky SS, and Giannobile WV, Relationship between C-telopeptide pyridinoline cross-links
(ICTP) and putative periodontal pathogens in periodontitis, Journal of Clinical Periodontology,1998, vol. 25, no. 11, pp. 865
871.

Impact Factor (JCC): 1.9876

Index Copernicus Value (ICV): 6.1

C-Telopeptide as Diagnostic Marker for Active Periodontal Destruction- A Review

9.

Giannobile WV. C-telopeptide pyridinoline cross-links. Sensitive indicators of periodontal tissue destruction. Ann N Y Acad
Sci 1999: 878: 404412

10. Mancini S, Romanelli R, Laschinger CA, et al. Assessment of a novel screening test for neutrophil collagenase activity in the
diagnosis of periodontal diseases. J Periodontol 1999; 567- 577 70(11):1292302.
11. Raed Al Rowis, Hani S Al Moharib, Abdulrahman Al Mubarak, Jagankumar Bhaskardoss etal. Oral Fluid-Based Biomarkers
in Periodontal Disease Part 2. Gingival Crevicular Fluid J Int Oral Health. 2014 Sep-Oct; 6(5): 126135.
12. Buduneli N, Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in
periodontitis. J Clin Periodontol. 2011;38(Suppl 11):85105.
13. Brgger U. Radiographic parameters: Biological significance and clinical use. Periodontol 2000. 2005;39:7390.
14. Schafer AL, Palermo L, Bauer DC, Bilezikian JP, etal. Consistency of bone turnover marker and calcium responses to
parathyroid hormone therapy in postmenopausal osteoporosis. J Clin Densitom. 2011 Jan-Mar; 14(1): 68-73.)
15. Lai PS, Chua SS, Chew YY, Chan SP. Effects ofsphosphonates in postmenopausal osteoporotic women. JClin Pharm Ther.
2011 Oct;36(5):557-67.
16. Murthy MB. Osteoimmunology - Unleashing the concepts. J Indian Soc Periodontol 2011 Jul 15 (3):190-8
17. Caki S. Gingival crevicular fluid in the diagnosis ofperiodontal and systemic diseases. Srp Arh Celok Lek.2009 MayJun;137(5-6):298-303.
18. Talonpoika JT, Hamalainen MM. Type I collagen carboxyterminal telopeptide in human gingival crevicular fluid in different
clinical conditions and after periodontal treatment. J Clin Periodontol 1994: 21: 320326.
19. Oringer RJ, Palys MD, Iranmanesh A, Fiorellini JP, etal. C-telopeptide pyridinoline cross-links (ICTP) and periodontal
pathogens associated with endosseous oral implants. Clin Oral Implants Res 1998: 9: 365373.
20. Mazur IP Features of bone tissue metabolic processes in patients with generalized periodontitis in the period of disease
exacerbation Gerontologija 2006; 7(4): 173179
21. Looker A, Bauer D, Chesnut C,et al. Clinical use of biochemical markers of bone remodeling:current status and future
directions. Osteoporos Int 2000;11: 467-80.
22. Robins S. Collagen turnover in bone diseases. Curr Opin Clin Nutr Metab Care 2003;6:65-71.
23. Brown J, Cook R, Major P, Lipton A, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer,
lung cancer, and other solid tumors. J Natl Cancer Inst 2005;97:59-69.
24. Souberbielle J, Cormier C, Kindermans C. Bone markers in Clinical practice. Curr Opin Rheumatol 1999;11:312-9.
25. Garnero P, Delmas P. Noninvasive techniques for assessing skeletal changes in inflammatory arthritis: bone markers. Curr
Opin Rheumatol 2004;16:428-34.
26. Terpos E, Politou M, Rahemtulla A. The role of markers of bone remodeling in multiple myeloma. Blood Rev 2005;19:125-42.
27. Lipton A, Costa L, Ali S, Demers L. Use of markers of bone turnover for monitoring bone metastases and the response to
therapy. Sem Oncol 2001;28(4 Suppl 11):54-9.
28. Risteli J, Melkko J, Niemi S, Risteli L. Use of a marker of collagen formation in osteoporosis studies. Calcif Tissue Int.
1991;49 Suppl:S24-5.

www.tjprc.org

editor@tjprc.org

10

P.R.Ganesh
29. Hannon R, Eastell R. Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 2000;11(Suppl
6):S30-44.
30. Reinhardt RA, Stoner JA, Golub LM, Lee HM, et al. Association of gingival crevicular fluid biomarkers during periodontal
maintenance with subsequent progressive periodontitis. J Period-ontol. 2010 Feb; 81(2):251-9.
31. Glover S, Garnero P, Naylor K, Rogers A, Eastell R. Establishing a reference range for bone turnover markers in young,
healthy women. Bone 2008;42:623-30.
32. Hannon R, Eastell R. Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 2000;11(Suppl
6):S30-44.
33. Giannobile WV, Beikler T, Kinney JS Ramseir C, Saliva as a diagnostic tool for periodontal disease: current state and future
directions, Periodontology 2000, 2009, Vol. 50: 5264.
34. Giannobile WV. Periodontal surveillance implications in the promotion of public health. J Periodontol 2007: 78: 1177
35. Christodoulides N, Mohanty S, Miller CS, Langub MC etal. Application of microchip assay system for the measurement of Creactive protein in human saliva. Lab Chip 2005: 5: 261269.
36. Herr AE, Hatch AV, Throckmorton DJ, Tran HM, Brennan JS, etal. Microfluidic immunoassays as rapid saliva-based clinical
diagnostics. Proc Natl Acad Sci U S A 2007: 104: 52685273.
37. Khashu H, Baiju CS, Bansal SR, Chhillar A, Salivary biomarkers: a periodontal overview,Journal of Oral Health &
Community Dentistry, 2012, vol. 6, pp. 2833.
38. Loos BG, Tjoa S. Host-derived diagnostic markers for periodontitis: do they exist in gingival crevice fluid? Periodontol 2000
2005: 39: 5372.
39. Al-Shammari KF, Giannobile WV, Aldredge WA, et al. Effect of non-surgical periodontal therapy on C-telopeptide
pyridinoline cross-links (ICTP) and interleukin-1 levels. J Periodontol 2001;72(8):104551.

Impact Factor (JCC): 1.9876

Index Copernicus Value (ICV): 6.1