SUMMARYElevated soluble thrombomodulin (sTM) levels are an accepted marker of endothelial damage. The physiological significance of plasma endothelial protein C receptor (sEPCR) levels is not known. To assess the relevance of this plasma protein in Wegener's granulomatosis (WG), sEPCR levels were measured in sera obtained from WG patients and related to disease activity, sTM levels, and other known markers of disease activity. In total, 129 sera (37 at active disease, 92 during follow-up) from 31 WG patients were tested. During active disease, eight (22%) and 17 (46%) out of 37 active sera had elevated levels of sEPCR and sTM, respectively (NS); sEPCR (r = 0·39; P = 0·02) and sTM (r = 0·53; P < 0·01) levels correlated with disease activity (Birmingham Vasculitis Activity Score). Analysis of longitudinal sera revealed a significant increase in sEPCR (P = 0·01) and sTM (P = 0·04) levels prior to the moment of a relapse. Corrected for renal function, the increase in sEPCR remained significant (P = 0·04) whereas sTM did not (NS). Levels of sEPCR correlated with sTM levels (r = 0·32; P < 0·001). Plasma levels of sEPCR respond to changes in the disease in patients with WG.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a relapsing-remitting disease, which is treated with corticosteroids (CS) in combination with cyclophosphamide. One of the major side-effects of this treatment is osteoporosis, which may result in the increased occurrence of fractures. In the present study we measured the prevalence of reduced bone mineral density (BMD) in a cross-sectional cohort of patients and correlated BMD findings with cumulative doses of CS and/or cyclophosphamide. BMD was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, radius and proximal femur between January 1998 and December 1999. Cumulative doses of CS and cyclophosphamide were calculated by chart review. Ninety-nine consecutive patients (48 men, 51 women) aged 55 +/- 16 years (mean +/- SD) were studied 50 months (median; range 0-400 months) after a diagnosis of ANCA-associated vasculitis had been made. Sixty-nine patients were treated with 10.7 g (median cumulative dose; range 0.4-67.2 g) of CS, and 88 patients were treated with 34.1 g (median cumulative dose; range 0.8-324.3 g) of cyclophosphamide. Fifty-seven percent of the patients had osteopenia (T-score: -1 to -2.5 SD), and 21% had osteoporosis (T-score: <-2.5 SD) at least at one site. Thirty-four of 37 (92%) postmenopausal women, 9 of 14 (64%) premenopausal women, and 34 of 48 (71%) men had either osteopenia or osteoporosis. The mean age- and sex-adjusted BMD (Z-score) of the proximal femur in men was found to be significantly lower than zero. Cumulative dose of CS therapy showed an inverse relation with Z-scores at the lumbar spine (p = 0.035) and proximal femur (p = 0.011). Cumulative dose of cyclophosphamide was not correlated with Z-scores. Osteopenia and osteoporosis are thus frequently observed in patients with ANCA-associated vasculities. However, only in men is the mean Z-score significantly lower than zero. Cumulative dose of CS therapy is significantly associated with bone loss at the spine and femur.

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