The Open Rheumatology Journal




ISSN: 1874-3129 ― Volume 13, 2019

Pentosidine, an Advanced Glycation End-Product, May Reflect Clinical and Morphological Features of Hand Osteoarthritis



Martin Braun*, 1, Hana Hulejová1, Jindřiška Gatterová1, Mária Filková1, Andrea Pavelková1, Olga Šléglová1, Nikola Kaspříková2, Jiří Vencovský1, Karel Pavelka 1, Ladislav Šenolt*, 1
1 Institute of Rheumatology, Department of Experimental and Clinical Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
2 Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Prague, Czech Republic

Abstract

The study investigates pentosidine levels, an advanced glycation end-product, in patients with erosive and non-erosive hand osteoarthritis (HOA) and determine its potential association with clinical findings and imaging-defined joint damage.

Pentosidine was measured by HPLC in serum and urine of 53 females with HOA (31 erosive and 22 non-erosive HOA) and normalised to the total serum protein or urinary creatinine, respectively. Pain, joint stiffness and disability were assessed by the Australian/Canadian OA hand index (AUSCAN). The hand radiographs scored according to the Kallman grading scale were assessed to determine a baseline value and reassessed after two years.

The levels of urine pentosidine, but not of serum pentosidine, were higher in patients with erosive HOA than in non-erosive HOA (p=0.039). Urinary pentosidine correlated with CRP (r=0.302, p=0.031), ESR (r=0.288, p=0.041) and AUSCAN (r=0.408, p=0.003). Serum pentosidine, but not in urine, significantly correlated with the Kallman radiographic score in erosive HOA at the baseline (r=0.409, p=0.022) and after 2 years (r=0.385, p=0.032). However, when corrected for age and disease duration, only correlation between urine pentosidine and AUSCAN remained significant (r=0.397, p=0.004).

Our data suggest that serum and urine pentosidine levels may relate to the distinctive clinical and morphological features of HOA.

Keywords: Hand osteoarthritis (HOA), pentosidine, erosive disease, biomarker, radiographs..


Article Information


Identifiers and Pagination:

Year: 2012
Volume: 6
First Page: 64
Last Page: 69
Publisher Id: TORJ-6-64
DOI: 10.2174/1874312901206010064

Article History:

Received Date: 10/3/2012
Revision Received Date: 5/4/2012
Acceptance Date: 12/4/2012
Electronic publication date: 1/6/2012
Collection year: 2012

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© Braun et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to these authors at the Ladislav Šenolt, Institute of Rheumatology, Na Slupi 4, 128 50 Prague 2, Czech Republic; Tel: +420 234075330; Fax: +420 224914451; E-mails: braun@revma.cz or seno@revma.cz




INTRODUCTION

Osteoarthritis (OA) is the most prevalent rheumatic joint disease, and it affects approximately 15% of the population [1 Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States Arthritis Rheum 1998; 41(5): 778-99.]. The disease occurs and causes disability mostly among elders; however, hand OA (HOA) is also prevalent in middle-aged and post-menopausal women [2 Punzi L, Ramonda R, Sfriso P. Erosive osteoarthritis Best Pract Res Clin Rheumatol 2004; 18(5): 739-58.]. HOA is considered to be a subset of primary generalised nodal OA. HOA, particularly its erosive subset, is associated with substantial pain, stiffness and physical disability, which may be similar to those symptoms seen in patients with rheumatoid arthritis (RA) [3 Slatkowsky CB, Mowinckel P, Kvien TK. Health status and perception of pain: a comparative study between female patients with hand osteoarthritis and rheumatoid arthritis Scand J Rheumatol 2009; 38(5): 342-8.]. Erosive HOA is characterised by prominent local inflammation of hand joints, leading to central erosions of the distal and, less frequently, of the proximal interphalangeal joints [4 Olejárová M, Kupka K, Pavelka K, Gatterová J, Stolfa J. Comparison of clinical, laboratory, radiographic, and scintigraphic findings in erosive and nonerosive hand osteoarthritis. Results of a two-year study Joint Bone Spine 2000; 67(2): 107-2.]. Routine blood tests are not helpful, and no biomarker is currently of any specific value for monitoring or predicting OA in an individual patient.

The pathogenesis of OA is still unclear. However, the age-associated accumulation of advanced glycation end-products (AGEs) in joint tissues has been shown to contribute to molecular changes and pathologic alterations in articular cartilage, which then may be more susceptible to damage and development of OA [5 DeGroot J, Verzijl N, Jacobs KM, et al. Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage Osteoarthritis Cartilage 2001; 9(8): 720-6.-7 Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis Arthritis Rheum 2002; 46(1): 114-23.]. Pentosidine was characterised as a sensitive marker for all AGEs and was demonstrated to have increased levels in the articular cartilage [7 Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis Arthritis Rheum 2002; 46(1): 114-23., 8 Takahashi M, Kushida K, Ohishi T, et al. Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders Arthritis Rheum 1994; 37(5): 724-8.]. In our previous study, we demonstrated the presence of increased serum levels of pentosidine in patients with knee OA in comparison to healthy controls, and we found a positive correlation between the levels of pentosidine and of cartilage oligomeric matrix protein (COMP), a marker of articular cartilage damage [9 Senolt L, Braun M, Olejárová M, Forejtová S, Gatterová J, Pavelka K. Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein Ann Rheum Dis 2005; 64(6): 886-90.]. More recently, we also identified pentosidine as a potential marker with predictive value for radiographic joint damage in patients with knee OA [10 Pavelka K, Forejtová S, Olejárová M, et al. Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis Osteoarthritis Cartilage 2004; 12(4): 277-83.].

Based on our previous data, we were curious to explore the association between pentosidine levels and hand OA. In the present study, we therefore investigated levels of serum and urine pentosidine in female patients with erosive and non-erosive HOA and characterised their potential association with clinical findings and radiographic joint damage over time.

MATERIALS AND METHODOLOGY

Patients

The patients in this study were selected from the group of patients who had undergone radiographs of both hands at a baseline and again after two years in our previous studies [11 Filková M, Senolt L, Braun M, et al. Serum hyaluronic acid as a potential marker with a predictive value for further radiographic progression of hand osteoarthritis Osteoarthritis Cartilage 2009; 17(12): 1615-9.,12 Filková M, Lisková M, Hulejová H, et al. Increased serum adiponectin levels in female patients with erosive compared with non-erosive osteoarthritis Ann Rheum Dis 2009; 68(2): 295-6.]. Altogether, 53 female patients that fulfilled the American College of Rheumatology (ACR) criteria for HOA [13 Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand Arthritis Rheum 1990; 33(11): 1601-0.] were included, 31 with the erosive and 22 with the non-erosive disease. The erosive disease was characterised according to the radiographic criteria published by Pattrick [14 Pattrick M, Aldridge S, Hamilton E, et al. A controlled study of hand function in nodal and erosive osteoarthritis Ann Rheum Dis 1989; 48(12): 978-82.]. All patients were assessed for pain and effusion upon palpation, deformity and deviation. The Australian/Canadian OA hand index (AUSCAN) and Dreiser algo-functional index, a 10-item investigator-administered questionnaire, were evaluated [15 Bellamy N, Campbell J, Haraoui B, et al. Clinimetric properties of the AUSCAN Osteoarthritis Hand Index: an evaluation of reliability, validity and responsiveness Osteoarthritis Cartilage 2002; 10(11): 863-9., 16 Dreiser RL, Maheu E, Guillou GB, Caspard H, Grouin JM. Validation of an algofunctional index for osteoarthritis of the hand Rev Rhum Engl Ed 1995; 62(6 Suppl 1): 43S-53S.]. None of the patients had diabetes mellitus and/or renal disease that could influence the pentosidine levels. This study was designed in accordance with the Declaration of Helsinki (2000) of the World Medical Association and approved by the local ethical committee. All the participating patients signed informed consent. Their demographic data are summarised in Table 1.

Table 1

Demographic and Clinical Characteristics of Patients with Erosive and Non-Erosive Hand Osteoarthritis (HOA)




Table 2

Association of Pentosidine, Clinical and Morphological Features of HOA




Laboratory Analysis

Venous blood was drawn from all patients at the time of the urinary sample collection. Vacutainers with blood samples were centrifuged at 2000 rpm (600 g) for 10 minutes, and serum and urine samples were stored at –20°C until the time of analysis.

Pentosidine levels were measured in serum and urine samples by high performance liquid chromatography (HPLC) combined with sensitive fluorescent detection. Due to very low concentrations of pentosidine and complexity of the analyzed material, previous sample pretreatment was a necessary step. The samples were hydrolysed for 16 hours at 105°C in an aliquot of 35% HCl, the hydrolysate was purified and preconcentrated by solid phase extraction using the self-made purification columns filled with microgranular cellulose and the n-butyl alcohol/ acetic acid system was applied. The pentosidine-containing fraction was then desorbed with 0.05 mol/l hydrochloric acid, the extract was evaporated and the residue was reconstituted in a mobile phase containing 0.02 mol/l heptafluorobutyric acid, 0.01 mol/l ammonium sulphate and acetonitrile (linear gradient 12.5 – 25.0 % in 20 minutes). After this procedure the sample was applied into a thermostated (40°C) C18 reversed phase separation column (Separon SGX C18, 150x3 mm from Tessek; Prague, Czech Republic) of the HPLC system (Shimadzu, LC-10ADvp; Kyoto, Japan). The chromatographic system operated by the CLASS VP software enable the gradient flow of the mobile phase (flow rate 0.5 ml/ min.) and sensitive fluorescent detection (excitation/ emission wavelengths λ = 335/385 nm). Length of one chromatographic run was 30 minutes.

Pentosidine standard is not commercially available, so the synthetic pentosidine standard used for calibration was prepared in our laboratory by a modified version of the procedure kindly provided by Prof. V. M. Monnier (Case Western Reserve University, Cleveland, OH, USA) which is based on the unique polymer-analogical non-enzymatic reaction (using polymer form of lysine and the proper carbohydrates). The quantity and purity of the prepared standard was assessed by Dr. D. Sell (the same affiliation). A detailed description of the method was published earlier [17 Spacek P, Adam M. HPLC method for pentosidine determination in urine, serum and tissues as a marker of glycation and oxidation loading of the organism J Liq Chromatogr Relat Technol 2002; 25(12): 1807-20., 18 Spacek P, Adam M. Pentosidine in osteoarthritis: HPLC determination in body fluids and in tissues Rheumatol Int 2006; 26(10): 923-7.].

The urine pentosidine (U-PEN) levels were normalised to the creatinine levels to account for differences in urine concentrations, and the serum pentosidine (S-PEN) levels were normalised to the levels of total serum protein. The high sensitivity C-reactive protein (hsCRP), total serum protein and urinary creatinine levels were measured by standard biochemical methods using the biochemical analyser Olympus (model AU 400, Japan).

Imaging

Each patient underwent posteroanterior plain radiographs of both hands at a baseline period and again after two years. Radiographs were scored by a trained reader according to the Kallman grading scale [19 Kallman DA, Wigley FM, Scott WW Jr, Hochberg MC, Tobin JD. New radiographic grading scales for osteoarthritis of the hand. Reliability for determining prevalence and progression Arthritis Rheum 1989; 32(12): 1584-91.]. Individual joints were assessed for the presence of osteophytes (graded 0-3), joint space narrowing (0-3), subchondral sclerosis (0-1), subchondral cysts (0-1), lateral deformity (0-1), and the collapse of a central joint cortical bone (0-1). To exclude the impact of knee OA on the levels of serum pentosidine, radiographs of both knees were performed to obtain baseline images.

To evaluate the inflamed hand joints and bone remodeling, blood pool (second phase) images and late (third phase) images of the three-phase bone scintigraphy were performed following a bolus injection of 600 MBq of Tc-99m methylene disphosphonate into an antecubital vein. All of the planar anterior images that were focused on the small hand joints were interpreted by the same radiologist. Hand joints were considered inflamed when the blood pool images indicated increased indicator uptake. Osteoblastic activity representing bone remodeling was established by increased indicator uptake in the late phase. For the purpose of this study, the total number of positive joints was calculated.

Statistical Analysis

Statistical analysis was done using GraphPad Prism 5 (GraphPad Prism Software Inc.) and SAS statistical software (version 9.2; www.sas.com). For comparison between the two groups, Mann-Whitney test was used. The results were expressed as the mean ± standard deviation (SD). Significance level 0.05 was used. Nonparametric analysis of correlations was performed, when variables were not normally distributed, using Spearman correlation coefficient (r) or partial Spearman correlation coefficients (rho). Multivariate correlation analysis of dependence between variables of interest (U-PEN, S-PEN, Kallman scores, CRP, ESR) was performed, and partial Spearman correlation coefficients were computed, adjusted for both age and disease duration.

RESULTS

This study was designed to particularly recruit patients with erosive HOA; therefore more patients with the erosive disease than with the non-erosive disease were enrolled in this study. The patients in the two groups did not significantly differ in terms of age, sex, disease duration, acute phase reactants or the presence of knee OA (Table 1). However, patients with the erosive disease used more non-steroidal anti-inflammatory drugs (NSAIDs), had more tender and swollen joints, had more deformities and deviations, and had more joint damage and inflammation as assessed by hand radiographs and scintigraphy than the patients with the non-erosive disease (Table 1).

Pentosidine and Clinical Findings

The levels of serum pentosidine that were normalised to the total protein content in patients with erosive HOA were comparable to those in patients with the non-erosive disease (1.06±0.61 vs 0.95±0.34 nmol/g; p=0.678) as shown in Fig. (1A). On the other hand, the urinary levels of pentosidine that were normalised to the urinary creatinine concentrations were significantly higher in erosive than in non-erosive HOA (2.69±1.66 vs 2.42±1.90 nmol/mmol, p=0.039) as shown in Fig. 1B). Using univariate analysis, in all patients with HOA, we found a significant correlation between the levels of serum and urinary pentosidine (r=0.343, p=0.013). The levels of urinary, but not serum, pentosidine correlated significantly with both CRP (r=0.302, p=0.031) and ESR (r=0.288, p=0.041). While the serum levels of pentosidine did not correlate with the measures of disease activity, pain, stiffness or number of swollen joints, the levels of urine pentosidine significantly correlated with the dimensions of joint pain, stiffness and disability as assessed by AUSCAN (r=0.408, p=0.003). However, the urine pentosidine levels did not correlate with the Dreiser algo-functional index. A trend of association between the urinary pentosidine levels and the total number of tender joints (r=0.269, p=0.054), but not with the number of swollen joints (r=-0.142, p=0.316) was observed. When adjusted for age and disease duration, correlation between urine pentosidine and AUSCAN remained significant (r=0.397, p=0.004) (Table 2).

Fig. (1)

Serum (A) and urinary pentosidine (B) in patients with erosive and non-erosive hand osteoarthritis (HOA). The serum pentosidine levels were normalised to the levels of total serum protein (S-PEN/TP), and the urine pentosidine levels were normalised to the creatinine levels (U-PEN/cr.). The horizontal lines represent the median value.



Fig. (2)

Correlations of S-PEN with Kallman radiographic scores in HOA: (A) baseline, (B) after two years. The shown graphs were constructed from the data without adjustment to age and disease duration. Abbreviations: S-PEN/TP = serum pentosidine levels normalised to the levels of total serum protein; HOA = hand osteoarthritis; r = Spearman correlation coefficient; p = statistical significance.



Pentosidine and Structural Joint Damage

Patients with the erosive disease had more severely affected hand joints, as assessed by both radiographs and scintigraphy, than those with the non-erosive disease (Table 1). As expected, the mean radiographic progression and scintigraphic progression over a period of two years were much faster with the erosive than with the non-erosive disease (Table 1). In all patients with HOA, the levels of serum and urine pentosidine did not correlate with the baseline joint radiographic damage (r=0.122, p=0.383 and r=0.173, p=0.219; respectively) or with the damage observed after two years (r=0.109, p=0.439 and r=0.166, p=0.238; respectively). However, in a subgroup of patients with the erosive disease, the levels of serum pentosidine significantly correlated with the Kallman baseline radiographic score and with the score determined after 2 years (r=0.409, p=0.022 and r=0.385, p=0.032; respectively) as shown in Fig. (2). On the contrary, urinary pentosidine levels did not correlate with the baseline Kallman radiographic score or with the radiographic score determined after 2 years (r=0.266, p=0.148 and r=0.253, p=0.170; respectively), and this association was also not found in patients with the non-erosive disease in which little progression was seen. When corrected for age and disease duration, correlation between serum pentosidine and radiographic scores remained no longer significant (Table 2). The levels of serum and urinary pentosidine in both groups of patients were not associated with the number of joints positive for blood pool phase and late phase scintigraphy (data not shown).

DISCUSSION

In the present study, we demonstrate for the first time higher levels of urine pentosidine, but not of serum pentosidine, in patients with erosive than in those with non-erosive hand OA. Additionally, the urine levels of pentosidine corrected for age and disease duration correlated significantly with assessments of joint pain, stiffness and disability in patients with HOA.

The levels of pentosidine were previously shown to be increased mostly under the conditions of inflammation, and they were associated with the laboratory and clinical disease activity in patients with RA [8 Takahashi M, Kushida K, Ohishi T, et al. Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders Arthritis Rheum 1994; 37(5): 724-8., 20 Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis Br J Rheumatol 1997; 36(6): 637-42., 21 Chen JR, Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis J Rheumatol 1998; 25(12): 2440-4.]. Patients with OA have significantly lower levels of urine pentosidine than those with RA [20 Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis Br J Rheumatol 1997; 36(6): 637-42.]. Although the levels of CRP were within the normal range in both groups of HOA patients, we found a positive correlation between the urinary pentosidine levels and acute phase reactants in patients with HOA. However, we did not observe this association with the levels of serum pentosidine, which is concurrent with two recent studies showing that the levels of serum pentosidine and other AGEs do not always reflect the disease activity in patients with RA [22 Senolt L, Braun M, Vencovský J, Sedová L, Pavelka K. Advanced glycation end-product pentosidine is not a relevant marker of disease activity in patients with rheumatoid arthritis Physiol Res 2007; 56(6): 771-7., 23 Vytásek R, Sedová L, Vilím V. Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis BMC Musculoskelet Disord 2010; 11: 83.]. Our data also show that the levels of urinary pentosidine are related to the measurements of joint pain, stiffness and disability that were assessed by AUSCAN in patients with HOA. On the other hand, the levels of urinary pentosidine did not correlate with the degree of radiographic changes of finger joints. This may be consistent with recent data showing that urinary pentosidine levels do not correlate with radiographic changes in large joints [24 Vos PA, DeGroot J, Huisman AM, et al. Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK) Osteoarthritis Cartilage 2010; 18(10): 1329-36.] and do not predict knee cartilage loss in patients with knee OA [25 Hunter DJ, Lavalley M, Li J, et al. Urinary pentosidine does not predict cartilage loss among subjects with symptomatic knee OA: the BOKS Study Osteoarthritis Cartilage 2007; 15(1): 93-7.].

The non-enzymatic glycation of proteins such as collagen or aggrecan in articular cartilage contributes to the formation of AGEs. This process is associated with ageing and results in increased cartilage stiffness, increased degradation of extracellular matrix proteins and decreased proteoglycan synthesis by chondrocytes [5 DeGroot J, Verzijl N, Jacobs KM, et al. Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage Osteoarthritis Cartilage 2001; 9(8): 720-6.]. Even though the presence of AGEs in articular cartilage is not specifically related to OA, the age-related accumulation of AGEs in the cartilage is likely to play a role in the pathogenesis of the disease [5 DeGroot J, Verzijl N, Jacobs KM, et al. Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage Osteoarthritis Cartilage 2001; 9(8): 720-6.-7 Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis Arthritis Rheum 2002; 46(1): 114-23., 26 Saudek DM, Kay J. Advanced glycation endproducts and osteoarthritis Curr Rheumatol Rep 2003; 5(1): 33-40.]. Pentosidine represents an adequate marker for all AGEs, and it is found in articular cartilage, serum, urine and synovial fluid [7 Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis Arthritis Rheum 2002; 46(1): 114-23.-10 Pavelka K, Forejtová S, Olejárová M, et al. Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis Osteoarthritis Cartilage 2004; 12(4): 277-83., 17 Spacek P, Adam M. HPLC method for pentosidine determination in urine, serum and tissues as a marker of glycation and oxidation loading of the organism J Liq Chromatogr Relat Technol 2002; 25(12): 1807-20., 18 Spacek P, Adam M. Pentosidine in osteoarthritis: HPLC determination in body fluids and in tissues Rheumatol Int 2006; 26(10): 923-7., 20 Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis Br J Rheumatol 1997; 36(6): 637-42.-22 Senolt L, Braun M, Vencovský J, Sedová L, Pavelka K. Advanced glycation end-product pentosidine is not a relevant marker of disease activity in patients with rheumatoid arthritis Physiol Res 2007; 56(6): 771-7., 25 Hunter DJ, Lavalley M, Li J, et al. Urinary pentosidine does not predict cartilage loss among subjects with symptomatic knee OA: the BOKS Study Osteoarthritis Cartilage 2007; 15(1): 93-7.]. Recently, urinary pentosidine levels were found to be elevated in patients with knee and hip OA in comparison to healthy control group individuals [18 Spacek P, Adam M. Pentosidine in osteoarthritis: HPLC determination in body fluids and in tissues Rheumatol Int 2006; 26(10): 923-7.]. We also reported elevated levels of serum pentosidine in patients with knee OA and an association between the levels of pentosidine, the local cartilage degrading marker COMP and radiographic knee joint damage [9 Senolt L, Braun M, Olejárová M, Forejtová S, Gatterová J, Pavelka K. Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein Ann Rheum Dis 2005; 64(6): 886-90., 10 Pavelka K, Forejtová S, Olejárová M, et al. Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis Osteoarthritis Cartilage 2004; 12(4): 277-83.]. Furthermore, the non-enzymatic glycation of collagen type I and the accumulation of pentosidine are also associated with osteoporosis and can induce the deterioration of bone quality [27 Wang X, Shen X, Li X, Agrawal CM. Age-related changes in the collagen network and toughness of bone Bone 2002; 31(1): 1-7.]. Although we found no difference in the levels of serum pentosidine between patients with erosive and non-erosive HOA, we observed a significant association between the levels of serum pentosidine and radiographic changes in patients with the erosive disease. It can be therefore hypothesised that the levels of pentosidine may reflect the progressive bone and cartilage damage in erosive HOA. In that sense, our results may be similar to the recent finding of the C-terminal cross-linking telopeptides of type I collagen being correlated with the radiographic changes in patients with erosive HOA [28 Scarpellini M, Lurati A, Vignati G, et al. Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the "Magenta osteoarthritis study" J Orthop Traumatol 2008; 9(2): 81-7.]. Because systemically measured pentosidine and other circulating biomarkers reflect whole body cartilage or bone degradation, they may be related to the severity of all joints affected by OA. Moreover, when the serum pentosidine was corrected for age and disease duration, its association with the degree of joint damage was no longer significant. These limitations have to be considered while interpreting the results of this and other studies.

CONCLUSIONS

In conclusion, the results of this study demonstrated increased levels of urine pentosidine in patients with erosive hand OA in comparison to those with non-erosive disease and suggested that the urine pentosidine is related to subclinical inflammation and measures of joint pain, stiffness and disability in patients with hand OA. Further studies are necessary to show whether pentosidine can be used as a surrogate marker of severity in age-related diseases such as OA.

ACKNOWLEDGEMENT

The study was supported by The Ministry of Health of The Czech Republic – research project No. 00023728.

CONFLICT OF INTEREST

The authors declare there is no conflict of interest.

REFERENCES

[1] Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States Arthritis Rheum 1998; 41(5): 778-99.
[2] Punzi L, Ramonda R, Sfriso P. Erosive osteoarthritis Best Pract Res Clin Rheumatol 2004; 18(5): 739-58.
[3] Slatkowsky CB, Mowinckel P, Kvien TK. Health status and perception of pain: a comparative study between female patients with hand osteoarthritis and rheumatoid arthritis Scand J Rheumatol 2009; 38(5): 342-8.
[4] Olejárová M, Kupka K, Pavelka K, Gatterová J, Stolfa J. Comparison of clinical, laboratory, radiographic, and scintigraphic findings in erosive and nonerosive hand osteoarthritis. Results of a two-year study Joint Bone Spine 2000; 67(2): 107-2.
[5] DeGroot J, Verzijl N, Jacobs KM, et al. Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage Osteoarthritis Cartilage 2001; 9(8): 720-6.
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[9] Senolt L, Braun M, Olejárová M, Forejtová S, Gatterová J, Pavelka K. Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein Ann Rheum Dis 2005; 64(6): 886-90.
[10] Pavelka K, Forejtová S, Olejárová M, et al. Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis Osteoarthritis Cartilage 2004; 12(4): 277-83.
[11] Filková M, Senolt L, Braun M, et al. Serum hyaluronic acid as a potential marker with a predictive value for further radiographic progression of hand osteoarthritis Osteoarthritis Cartilage 2009; 17(12): 1615-9.
[12] Filková M, Lisková M, Hulejová H, et al. Increased serum adiponectin levels in female patients with erosive compared with non-erosive osteoarthritis Ann Rheum Dis 2009; 68(2): 295-6.
[13] Altman R, Alarcón G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand Arthritis Rheum 1990; 33(11): 1601-0.
[14] Pattrick M, Aldridge S, Hamilton E, et al. A controlled study of hand function in nodal and erosive osteoarthritis Ann Rheum Dis 1989; 48(12): 978-82.
[15] Bellamy N, Campbell J, Haraoui B, et al. Clinimetric properties of the AUSCAN Osteoarthritis Hand Index: an evaluation of reliability, validity and responsiveness Osteoarthritis Cartilage 2002; 10(11): 863-9.
[16] Dreiser RL, Maheu E, Guillou GB, Caspard H, Grouin JM. Validation of an algofunctional index for osteoarthritis of the hand Rev Rhum Engl Ed 1995; 62(6 Suppl 1): 43S-53S.
[17] Spacek P, Adam M. HPLC method for pentosidine determination in urine, serum and tissues as a marker of glycation and oxidation loading of the organism J Liq Chromatogr Relat Technol 2002; 25(12): 1807-20.
[18] Spacek P, Adam M. Pentosidine in osteoarthritis: HPLC determination in body fluids and in tissues Rheumatol Int 2006; 26(10): 923-7.
[19] Kallman DA, Wigley FM, Scott WW Jr, Hochberg MC, Tobin JD. New radiographic grading scales for osteoarthritis of the hand. Reliability for determining prevalence and progression Arthritis Rheum 1989; 32(12): 1584-91.
[20] Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis Br J Rheumatol 1997; 36(6): 637-42.
[21] Chen JR, Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis J Rheumatol 1998; 25(12): 2440-4.
[22] Senolt L, Braun M, Vencovský J, Sedová L, Pavelka K. Advanced glycation end-product pentosidine is not a relevant marker of disease activity in patients with rheumatoid arthritis Physiol Res 2007; 56(6): 771-7.
[23] Vytásek R, Sedová L, Vilím V. Increased concentration of two different advanced glycation end-products detected by enzyme immunoassays with new monoclonal antibodies in sera of patients with rheumatoid arthritis BMC Musculoskelet Disord 2010; 11: 83.
[24] Vos PA, DeGroot J, Huisman AM, et al. Skin and urine pentosidine weakly correlate with joint damage in a cohort of patients with early signs of osteoarthritis (CHECK) Osteoarthritis Cartilage 2010; 18(10): 1329-36.
[25] Hunter DJ, Lavalley M, Li J, et al. Urinary pentosidine does not predict cartilage loss among subjects with symptomatic knee OA: the BOKS Study Osteoarthritis Cartilage 2007; 15(1): 93-7.
[26] Saudek DM, Kay J. Advanced glycation endproducts and osteoarthritis Curr Rheumatol Rep 2003; 5(1): 33-40.
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[28] Scarpellini M, Lurati A, Vignati G, et al. Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the "Magenta osteoarthritis study" J Orthop Traumatol 2008; 9(2): 81-7.

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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