Monitoring of free and total urinary pyridinoline and deoxypyridinoline in healthy volunteers: sample relationships between 24-h and fasting early morning urine concentrations

Abbiati, G.; Bartucci, F.; Longoni, A.; Fincato, G.; Galimberti, Stefania; Rigoldi, M.; Castiglioni, Carlo Andrea

doi:10.1016/s0169-6009(08)80116-x

Cited by 32 publications

(10 citation statements)

References 19 publications

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“…Our results showed a higher share of free crosslinks in the normal volunteers (fig 1) than those of Abbiati et al, 13 who found 50% for both, and Knott and Bailey, 4 who found 40%. However, our chromatographic method is validated and the determination procedure includes an internal standard, allowing for improved intra-and interassay variation coefficients.…”

Section: Discussioncontrasting

confidence: 48%

Evaluation of free and peptide bound collagen crosslink excretion in different skeletal diseases

Müller¹,

Jakob²,

Hein³

2003

Annals of the Rheumatic Diseases

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Objective: To investigate urinary fractions of free and peptide forms of collagen crosslinks in patients with rheumatoid arthritis (n=50), osteoarthrosis (n=38), psoriatic arthritis (n=38) and in healthy volunteers (33 adults, 17 children). Methods: Pyridinoline (PYD) and deoxypyridinoline (DPD) were measured by high performance liquid chromatography. Results: In rheumatoid arthritis (RA) all fractions of PYD and DPD were significantly raised compared with osteoarthritis, psoriatic arthritis, and healthy controls. PYD and DPD correlated with disease activity in RA. In RA the collagen degradation resulted in primarily peptide bound forms. Conclusion:The correlation between total peptide bound or free collagen crosslinks in different chronic joint diseases varies; however, this variation does not allow for a reliable differentiation between inflammatory and degenerative joint diseases. P yridinoline (PYD), a trifunctional 3-hydroxypyridinium crosslink 1 and its analogue, deoxypyridinoline (DPD), 2 are two non-reducible collagen crosslinks. PYD occurs in type I and II collagen 3 and, with the exception of skin, sclerae, and cornea, in most connective tissues-that is, bone and cartilage. DPD originates mainly from bone.3 When collagen fibrils are degraded into molecular fragments as a result of osteoclastic resorption, PYD and DPD are released into the circulation. They are then cleared by the kidney and excreted through urine, where they can be detected in peptide bound and free forms. 4 It has been reported that 40% of these crosslinks are excreted into urine as free and 60% in the peptide bound form. 4 Yet it remains unclear whether the determination of free or peptide bound crosslinks can provide more information on a possibly different collagen catabolism in patients with different diseases, compared with healthy adults and children.The aim was to investigate the fractions of free and peptide bound crosslinks as well as the total excretion in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthrosis (OA) compared with healthy adults and children. Inflammation markers and steroid dose were included in further correlation studies. Healthy children were investigated to discover possible differences due to growth. SUBJECTS AND METHODS Healthy controlsFifty healthy volunteers were included (33 healthy adults (HA), 12 female, 21 male, mean (SD) age 41.0 (7.8) years and 17 healthy children (HC), nine female, eight male, mean (SD) age 7.7 (3.3) years). None had a previous history of metabolic bone disease, and none were receiving drugs affecting calcium absorption, excretion, or bone metabolism. Rheumatoid arthritisThis group included 44 female and six male patients, mean age 54.9 (15.9) years with definite RA. To determine the disease activity, serum C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured. The daily steroid dose was also recorded. OsteoarthritisThis group included 38 patients with proven OA of the knee joints (30 female, eight male, mean age 59.0 (1...

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Section: Discussioncontrasting

confidence: 48%

Evaluation of free and peptide bound collagen crosslink excretion in different skeletal diseases

Müller¹,

Jakob²,

Hein³

2003

Annals of the Rheumatic Diseases

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“…14 There are inconsistent reports on the correlation between measurements made on 24 hour urine collections and early morning samples,3 14 19 20 and it is unknown whether pyridinium crosslink excretion measured in a 24 hour urine sample offers any advantage over the use of a first morning void sample. In postmenopausal women, measurement of DPyr and Pyr in first morning void urine samples more closely reflects the rate of bone loss compared with the measurement in 24 hour urine samples 19…”

Section: Discussionmentioning

confidence: 99%

Urinary excretion of pyridinium crosslinks in healthy 4-10 year olds

Husain

Mughal

Williams

et al. 1999

Archives of Disease in Childhood

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Urinary pyridinoline and deoxypyridinoline, pyridinium crosslinks released during breakdown of mature collagen, might serve as useful markers of bone resorption. Before their role can be identified, reference values must be established. In this study, free pyridinoline (f-Pyr), free deoxypyridinoline (f-DPyr), and creatinine (Cr) were measured in first morning void urine samples from 250 girls and 265 boys between the ages of 4 and 10 years. Overall, there was a decrease in f-Pyr:Cr and f-DPyr:Cr ratios with increasing age in both sexes, but there was a wide range of values for individuals of similar ages. Further studies are required to assess whether urinary pyridinium crosslink excretion is suYciently deranged in conditions aVecting bone metabolism for the measurement of these compounds to be of clinical value. (Arch Dis Child 1999;80:370-373) Keywords: pyridinoline; deoxypyridinoline; bone resorption Certain biochemical markers of bone turnover might prove to be of clinical use in conditions and treatments that aVect bone metabolism. Markers of bone formation include osteocalcin, bone specific alkaline phosphatase, and propeptides derived from type I collagen, all of which have the disadvantage of requiring a serum sample for their measurement; whereas markers of bone resorption, including calcium, hydroxyproline, hydroxylysine glycosides, telopeptides and pyridinium collagen crosslinks, can be measured in urine. Until recently, urinary hydroxyproline was the best established marker of bone resorption. However, urinary hydroxyproline is influenced by dietary intake, is metabolised extensively in the liver, and is not specific for bone collagen.1 Pyridinoline (Pyr) and deoxypyridinoline (DPyr) are non-reducible pyridinium compounds that crosslink mature collagen chains within extracellular matrices and are released into the circulation during collagen resorption. Unlike hydroxyproline, urinary excretion of Pyr and DPyr is not influenced by dietary intake 1 and is more specific for resorption of bone collagen. 2In adults, ∼ 30-40% of pyridinium crosslinks appear free in urine, with the remainder in peptide form. The measurement of total urinary pyridinium crosslinks in adults has shown good correlation between Pyr and DPyr excretion and bone turnover as assessed by radioisotopic 4 and histomorphometric 5 techniques, but corresponding data in children are not available. The clinical usefulness of measuring pyridinium crosslinks in adult urine has been shown in a variety of bone diseases including rheumatoid arthritis, osteoarthritis, primary hyperparathyroidism, hyperthyroidism, Paget's disease, osteomalacia, osteoporosis, and metastatic bone disease. 6 If the urinary excretion of Pyr and DPyr is to be of any value in assessing bone resorption in conditions or treatments that might aVect bone turnover in children, then normal ranges for the excretion of these crosslinking amino acids must be established. However, there are few data on urinary pyridinium crosslink excretion in healthy children. Shaw e...

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“…The method was later automated [119] and, more recently, automated techniques for the measurement in serum have been described [120]. Analysis of urine by HPLC without initial hydrolysis showed that 40±50% of the crosslinks were present in the peptide free form [121,122]. Since this proportion does not signi®cantly change with bone turnover or bone pathologies, measurement of the free crosslink fraction is likely to provide similar information about bone resorption.…”

Section: Hydroxypyridinium Crosslinks Of Collagenmentioning

confidence: 99%

Molecular Markers of Bone Turnover: Biochemical, Technical and Analytical Aspects

Seibel

2000

Osteoporosis International

151

114

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Monitoring of free and total urinary pyridinoline and deoxypyridinoline in healthy volunteers: sample relationships between 24-h and fasting early morning urine concentrations

Cited by 32 publications

References 19 publications

Evaluation of free and peptide bound collagen crosslink excretion in different skeletal diseases

Evaluation of free and peptide bound collagen crosslink excretion in different skeletal diseases

Urinary excretion of pyridinium crosslinks in healthy 4-10 year olds

Molecular Markers of Bone Turnover: Biochemical, Technical and Analytical Aspects

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