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Longitudinal and cross-sectional variability in markers of joint metabolism in patients with knee pain and articular cartilage abnormalities

Lohmander, L. Stefan LU ; Dahlberg, Leif LU ; Eyre, David; Lark, Michael; Thonar, Eugene J M A and Ryd, Leif LU (1998) In Osteoarthritis and Cartilage 6(5). p.351-361
Abstract

Objective: To determine the within- and between-patient variability in the concentrations of synovial fluid, serum and urine markers of joint tissue metabolism in a cohort of patients with knee pain and cartilage changes consistent with early-stage knee osteoarthritis. Design: Samples of synovial fluid, serum, and urine were obtained from 52 patients on eight different occasions during 1 year, as part of a clinical trial in patients with cartilage abnormalities and knee pain. In joint fluid, aggrecan fragments were quantified by dye precipitation and enzyme-linked immunosorbent assay (ELISA), and matrix metalloproteinases-1 and -3, and tissue inhibitor of metalloproteinases-1 by sandwich ELISAs. In serum, keratan sulfate was quantified... (More)

Objective: To determine the within- and between-patient variability in the concentrations of synovial fluid, serum and urine markers of joint tissue metabolism in a cohort of patients with knee pain and cartilage changes consistent with early-stage knee osteoarthritis. Design: Samples of synovial fluid, serum, and urine were obtained from 52 patients on eight different occasions during 1 year, as part of a clinical trial in patients with cartilage abnormalities and knee pain. In joint fluid, aggrecan fragments were quantified by dye precipitation and enzyme-linked immunosorbent assay (ELISA), and matrix metalloproteinases-1 and -3, and tissue inhibitor of metalloproteinases-1 by sandwich ELISAs. In serum, keratan sulfate was quantified by ELISA. Type I collagen N-telopeptide cross-links in urine were determined by ELISA. Results: The degree of cross-sectional variability in marker concentrations did not vary between the different sampling occasions, and did not differ between the periods of weeks 0 (baseline), 1-4 (treatment) and 13-26 (follow-up). Both between-patient and within-patient coefficients of variation varied for markers in different body fluid compartments, with the lowest variability for serum keratan sulfate, followed by urine type I collagen N-telopeptide crosslinks, and the highest for synovial fluid markers. For synovial fluid, aggrecan fragments showed the least variability, and matrix metalloproteinases the highest. One patient with septic arthritis showed a fivefold peak increase in joint fluid aggrecan fragment concentrations, while the concentration of matrix metalloproteinase-3 increased 100-fold. Conclusions: Molecular markers of joint tissue metabolism have been suggested as, for example, outcome measures for clinical trials of disease-modifying drugs in osteoarthritis. This report is the first to present data on between- and within-patient variability for such molecular markers in three different body fluid compartments in stable cohort of patients. The availability of such data enables calculations to determine the number of patients needed in prospective studies using these markers as outcome measures.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Joint fluid markers, Knee, Osteoarthritis
in
Osteoarthritis and Cartilage
volume
6
issue
5
pages
11 pages
publisher
Elsevier
external identifiers
  • Scopus:0032170469
ISSN
1063-4584
DOI
10.1053/joca.1998.0134
language
English
LU publication?
no
id
440af844-e11f-49a4-bbd6-5b63d5e07169
date added to LUP
2016-05-04 23:58:28
date last changed
2016-10-13 05:08:03
@misc{440af844-e11f-49a4-bbd6-5b63d5e07169,
  abstract     = {<p>Objective: To determine the within- and between-patient variability in the concentrations of synovial fluid, serum and urine markers of joint tissue metabolism in a cohort of patients with knee pain and cartilage changes consistent with early-stage knee osteoarthritis. Design: Samples of synovial fluid, serum, and urine were obtained from 52 patients on eight different occasions during 1 year, as part of a clinical trial in patients with cartilage abnormalities and knee pain. In joint fluid, aggrecan fragments were quantified by dye precipitation and enzyme-linked immunosorbent assay (ELISA), and matrix metalloproteinases-1 and -3, and tissue inhibitor of metalloproteinases-1 by sandwich ELISAs. In serum, keratan sulfate was quantified by ELISA. Type I collagen N-telopeptide cross-links in urine were determined by ELISA. Results: The degree of cross-sectional variability in marker concentrations did not vary between the different sampling occasions, and did not differ between the periods of weeks 0 (baseline), 1-4 (treatment) and 13-26 (follow-up). Both between-patient and within-patient coefficients of variation varied for markers in different body fluid compartments, with the lowest variability for serum keratan sulfate, followed by urine type I collagen N-telopeptide crosslinks, and the highest for synovial fluid markers. For synovial fluid, aggrecan fragments showed the least variability, and matrix metalloproteinases the highest. One patient with septic arthritis showed a fivefold peak increase in joint fluid aggrecan fragment concentrations, while the concentration of matrix metalloproteinase-3 increased 100-fold. Conclusions: Molecular markers of joint tissue metabolism have been suggested as, for example, outcome measures for clinical trials of disease-modifying drugs in osteoarthritis. This report is the first to present data on between- and within-patient variability for such molecular markers in three different body fluid compartments in stable cohort of patients. The availability of such data enables calculations to determine the number of patients needed in prospective studies using these markers as outcome measures.</p>},
  author       = {Lohmander, L. Stefan and Dahlberg, Leif and Eyre, David and Lark, Michael and Thonar, Eugene J M A and Ryd, Leif},
  issn         = {1063-4584},
  keyword      = {Joint fluid markers,Knee,Osteoarthritis},
  language     = {eng},
  number       = {5},
  pages        = {351--361},
  publisher    = {ARRAY(0x9e92770)},
  series       = {Osteoarthritis and Cartilage},
  title        = {Longitudinal and cross-sectional variability in markers of joint metabolism in patients with knee pain and articular cartilage abnormalities},
  url          = {http://dx.doi.org/10.1053/joca.1998.0134},
  volume       = {6},
  year         = {1998},
}