Collagen crosslinks in fibromyalgia (FM)

OBJECTIVE: To determine if abnormal collagen metabolism is a

characteristic of fibromyalgia.

METHODS: The diagnosis of

fibromyalgia was made according to the American College of

Rheumatology criteria. Skin biopsy samples were obtained from

the trapezius region of 8 patients with fibromyalgia. Urine

was collected under standardized conditions from 55 control

subjects and 39 patients with fibromyalgia, and serum was

obtained from 17 controls and 22 patients with fibromyalgia.

Pyridinoline (Pyd), an indicator of connective tissue disease,

and deoxypyridinoline (Dpyd), an indicator of bone

degradation, both of which represent products of lysyl

oxidase-mediated crosslinking in collagen, were analyzed by

ion-paired and gradient high-performance liquid chromatography

(HPLC) methods with fluorescence detection. Levels of

hydroxyproline (Hyp), a collagen turnover marker, were also

measured. The findings were related to creatinine levels, and

the Pyd:Dpyd ratio was determined.

RESULTS: Highly ordered

cuffs of collagen were observed around the terminal nerve

fibers by electron microscopic examination of biopsy tissue

from all 8 patients with fibromyalgia, but were not observed

in any of the control skin samples. The Pyd:Dpyd ratios in the

urine and serum and the Hyp levels in the urine were

significantly lower in patients with fibromyalgia than in

healthy controls.

CONCLUSION: Decreased levels of collagen

crosslinking in fibromyalgia may contribute to remodeling of

the extracellular matrix and collagen deposition around the

nerve fibers, and may contribute to the lower pain threshold

at the tender points. Analysis of altered collagen metabolism

either by histologic examination on biopsy, or preferably, by

HPLC analysis of collagen metabolites in urine or serum may

aid in understanding more about the pathogenesis of


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