Collagen cross-links in fibromyalgia syndrome

Objective: The acceptance of fibromyalgia as a disease entity and its defin itive diagnosis have been hampered by a dearth of knowledge concerning the underlying pathophysiology of this disease and the lack of specific biochem ical markers applicable to its diagnosis. To determine whether abnormal col lagen metabolism is a characteristic of fibromyalgia, we have analyzed coll agen metabolites in the urine and serum of patients with fibromyalgia. Methods: The diagnosis of fibromyalgia was made according to the American C ollege of Rheumatology criteria. Urine and serum were collected under stand ardized conditions from 39 patients and 55 age- and sex-matched controls. P yridinoline (Pyd) and deoxypyridinoline (Dpyd), which represent products of lysyl oxidase-mediated cross-linking in collagen and are indicators of con nective tissue and bone degradation, respectively, were analyzed by ion-pai red and gradient HPLC method with fluorescence detection (HPLC). Levels of hydroxypyroline (Hyp), a collagen turnover marker, were also measured. The findings were related to creatinine levels and the Pyd/Dpyd ratio determine d. Results. The Pyd/Dpyd ratios in the urine and serum and the Hyp in the urin e were significantly lower in patients with fibromyalgia than in healthy co ntrols. Conclusion: Decreased levels of collagen cross-linking may contribute to re modeling of the extracellular matrix and collagen deposition around the ner ve fibers in fibromyalgia and contribute to the lower pain threshold at the tender points. Analysis of altered collagen metabolism either by histologi c examination on biopsy or, preferably, by HPLC analysis of collagen metabo lites in urine or serum may aid to understand more about the pathogenesis o f fibromyalgia.