British Journal of Rheumatology 1992;31:759-761
URINARY COLLAGEN CROSSLINKS REFLECT THE RADIOGRAPHIC SEVERITY OF KNEE OSTEOARTHRITIS BY P. W. THOMPSON*, T. D. SPECTORt, I. T. JAMES*, E. HENDERSON AND D. J. HARTf *The Bone and Joint Research Unit, the Medical College of the Royal London Hospital, London El 2 AD; tDepartments of Rheumatology and Environmental and Preventive Medicine, St Bartholomew's Hospital Medical College, London EC1
KEY WORDS:
Pyridinoline, Deoxypyridinoline, Pyridinium compounds, X-rays.
OSTEOARTHRITIS (OA) is the commonest cause of physical disability in the UK. It is characterized by loss of cartilage, bone remodelling and synovial reaction resulting in radiographic appearances of joint space narrowing, subchondral sclerosis and marginal osteophyte formation. The X-ray changes are easily recognized but are insensitive assessments of the severity of the disease processes and correlate poorly with symptoms [1,2]. Alternative methods are needed that allow the study of osteoarthritic processes in vivo. There has been considerable interest in the potential of putative 'biochemical markers' of cartilage metabolism in the assessment of OA. The principle is to measure substances in blood or urine that reflect the balance between cartilage matrix production and breakdown. The measurement of proteoglycan epitopes as potential markers of cartilage degeneration has been proposed [3,4]. Unfortunately the ability of these assays to distinguish cases and controls has been disappointing, possibly because of the small volume of cartilage involved in the processes [5]. An alternative approach is to measure biochemical markers of bone metabolism. Deoxypyridinoline (DPYR) is a collagen crosslink molecule produced as part of the maturation process of collagen and is found almost exclusively in bone. It is released from the bone matrix during remodelling and is an index of mature collagen breakdown. DPYR is excreted in the urine where levels are increased in a number of metabolic bone diseases characterized by increased bone turnover [6]. An analogue, pyridinoline (PYR), is distributed more widely in human connective tissues (including cartilage but not skin) and occurs in abundance in mature bone matrix [7]. This study was designed to examine differences between OA cases and controls and determine Submitted 2 July 1991; revised version accepted 22 October
whether urinary crosslink levels might act as a marker of severity of knee OA. METHODS Fifty-nine female patients (mean (SD) age = 66.7 (10.6) years) attending a rheumatology outpatients clinic with symptomatic bilateral knee osteoarthritis were compared with 110 normal post-menopausal women (mean (SD) age = 62.8 (4.8) years) randomly selected as part of a community based screening project. The following information was obtained: height, weight, joint symptoms, and current medication. Antero-posterior, weight-bearing X-rays of both knees were taken and graded using the standard radiographs of Kellgren and Lawrence [8] (grades 0-4) by a single experienced observer who was blinded to the source of subject. The grade used for analysis was the highest in either knee and grades 0 and 1 (doubtful category) were combined. Urinary crosslinks corrected for creatinine (cr) were measured on morning fasting samples by reverse phase, isocratic, ion-paired high performance liquid chromatography [9]. The coefficients of variation for these assays are less than 10% in our laboratory. Statistical comparison included Student's Mest and Pearson's correlation coefficient. The possible confounding effects of age and weight were examined using analysis of variance with SPSS software. RESULTS The OA patients were significantly older (P
URINARY COLLAGEN CROSSLINKS REFLECT THE RADIOGRAPHIC SEVERITY OF KNEE OSTEOARTHRITIS BY P. W. THOMPSON*, T. D. SPECTORt, I. T. JAMES*, E. HENDERSON AND D. J. HARTf *The Bone and Joint Research Unit, the Medical College of the Royal London Hospital, London El 2 AD; tDepartments of Rheumatology and Environmental and Preventive Medicine, St Bartholomew's Hospital Medical College, London EC1
KEY WORDS:
Pyridinoline, Deoxypyridinoline, Pyridinium compounds, X-rays.
OSTEOARTHRITIS (OA) is the commonest cause of physical disability in the UK. It is characterized by loss of cartilage, bone remodelling and synovial reaction resulting in radiographic appearances of joint space narrowing, subchondral sclerosis and marginal osteophyte formation. The X-ray changes are easily recognized but are insensitive assessments of the severity of the disease processes and correlate poorly with symptoms [1,2]. Alternative methods are needed that allow the study of osteoarthritic processes in vivo. There has been considerable interest in the potential of putative 'biochemical markers' of cartilage metabolism in the assessment of OA. The principle is to measure substances in blood or urine that reflect the balance between cartilage matrix production and breakdown. The measurement of proteoglycan epitopes as potential markers of cartilage degeneration has been proposed [3,4]. Unfortunately the ability of these assays to distinguish cases and controls has been disappointing, possibly because of the small volume of cartilage involved in the processes [5]. An alternative approach is to measure biochemical markers of bone metabolism. Deoxypyridinoline (DPYR) is a collagen crosslink molecule produced as part of the maturation process of collagen and is found almost exclusively in bone. It is released from the bone matrix during remodelling and is an index of mature collagen breakdown. DPYR is excreted in the urine where levels are increased in a number of metabolic bone diseases characterized by increased bone turnover [6]. An analogue, pyridinoline (PYR), is distributed more widely in human connective tissues (including cartilage but not skin) and occurs in abundance in mature bone matrix [7]. This study was designed to examine differences between OA cases and controls and determine Submitted 2 July 1991; revised version accepted 22 October
whether urinary crosslink levels might act as a marker of severity of knee OA. METHODS Fifty-nine female patients (mean (SD) age = 66.7 (10.6) years) attending a rheumatology outpatients clinic with symptomatic bilateral knee osteoarthritis were compared with 110 normal post-menopausal women (mean (SD) age = 62.8 (4.8) years) randomly selected as part of a community based screening project. The following information was obtained: height, weight, joint symptoms, and current medication. Antero-posterior, weight-bearing X-rays of both knees were taken and graded using the standard radiographs of Kellgren and Lawrence [8] (grades 0-4) by a single experienced observer who was blinded to the source of subject. The grade used for analysis was the highest in either knee and grades 0 and 1 (doubtful category) were combined. Urinary crosslinks corrected for creatinine (cr) were measured on morning fasting samples by reverse phase, isocratic, ion-paired high performance liquid chromatography [9]. The coefficients of variation for these assays are less than 10% in our laboratory. Statistical comparison included Student's Mest and Pearson's correlation coefficient. The possible confounding effects of age and weight were examined using analysis of variance with SPSS software. RESULTS The OA patients were significantly older (P
