Original ArticlesUncoupling of bone metabolism in rheumatoid arthritis patients with or without joint destruction: assessment with serum type I collagen breakdown products
Introduction
Chronic arthritis is characterized by synovial inflammation and, in its destructive form, by the degradation of articular cartilage and bone. Joint destruction is difficult to investigate because of the lack of specific and sensitive biochemical markers that could reflect the degree of severity related to joint destruction early in the disease.
Collagen is the most prominent protein of bone and cartilage matrices, type II being almost specific for cartilage, whereas type I, which predominates in bone, tendons, and ligaments, is also present in synovial membrane together with type III collagen. Collagen molecules are linked by cross-links such as pyridinoline and deoxypyridinoline in the C- and N-telopeptides.10 Degradation of joint tissues may thus be assessed by measuring the urinary excretion of pyridinoline cross-links.11 However, urinary markers have several limitations, including the need for control of sampling time5, 37 and for correction for urinary creatinine. A first serum-based assay measuring carboxyterminal type I collagen telopeptide (ICTP) has been developed.34 Increased ICTP levels have been found in active rheumatoid arthritis (RA) patients.17, 25 However, the tissue specificity and the clinical significance of serum ICTP levels are still unclear. In particular, ICTP levels increase after treatment with anabolic steroids, which are believed to decrease bone resorption and to stimulate collagen synthesis,21 and thus ICTP appears to be more a marker of collagen turnover than of bone resorption. Recently, a new serum bone resorption marker, using two monoclonal antibodies raised against synthetic peptides from type I collagen C-telopeptides (CTX) has been developed, and clinical data indicate that serum CTX levels reflect specific bone resorption.6
Most, if not all, studies have used biochemical markers of bone turnover in active RA characterized by joint destruction. In a previous study, we found decreased osteocalcin levels and increased urinary excretion of pyridinoline, deoxypyridinoline, and CTX in active RA patients, suggesting an imbalance between formation and resorption, which could be responsible for bone loss in such patients.18 In contrast, the situation in RA patients without evidence of joint destruction remains unknown.
The aim of this study was to assess abnormalities of bone turnover in a large group of RA patients with or without joint destruction using serum osteocalcin as a specific index of bone formation and a serum CTX assay to assess bone resorption.
Section snippets
Patients and controls
Three hundred eighteen RA patients were included in this study. All patients fulfilled the commonly used criteria for RA (American College of Rheumatology [ACR] criteria).1 All patients had a disease duration of at least 2 years. One hundred two patients were on low-dose steroids (<10 mg/day prednisone) and 45 on low-dose methotrexate (7.5–15 mg/week) at the time of evaluation. Patients with renal insufficiency were excluded.
Bone turnover in these patients was compared with that of 319 healthy
Bone turnover in patients with destructive and nondestructive arthritis
Patients with nondestructive and destructive arthritis were compared and results are shown in Table 1. Patients with destructive arthritis were slightly older with a disease duration slightly longer than that of nondestructive patients. The percentage of patients on corticosteroid or methotrexate treatment was higher among patients with destructive arthritis compared with nondestructive arthritis patients. As expected, the two groups of patients differed statistically for indices of disease
Discussion
Using bone turnover markers, including a new serum assay for type I collagen degradation, we found, in a large population of patients with chronic arthritis, that bone turnover was altered, not only in severe RA patients with joint destruction, but also in those with benign arthritis without evidence of altered joint structure. However, the pattern of bone metabolism was different in the two groups. In patients without joint destruction, bone resorption was not increased, whereas low levels of
Acknowledgements
The authors are grateful to Cécile Valverde for excellent technical assistance.
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