Prevalence of Reduced Bone Mineral Density in Patients with Anti-neutrophil Cytoplasmic Antibody Associated Vasculitis and the Role of Immunosuppressive Therapy: A Cross-Sectional Study

Abstract

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.

Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population

“…In a cross-sectional study of bone density in a cohort of patients with AAV from a tertiary center in the Netherlands, the prevalence of osteoporosis was 21% and of osteopenia, 57% 29 . Data on osteoporosis in AAV are scarce.…”

Avoidance of Harm From Treatment for ANCA-Associated Vasculitis

“…AAV alone is also associated with reduced BMD, although the mechanisms for this are not yet fully understood. In a cross-sectional study involving 99 patients with AAV treated with corticosteroids and cyclophosphamide, 78% of patients were found to have abnormal dual-energy X-ray absorptiometry (DEXA) measurements in one of three sites (the lumbar spine, proximal femur or radius); 21% of these patients had osteoporosis and 57% osteopenia [ 38 ]. Cumulative dosage of corticosteroid therapy was inversely related to Z-score; significant correlations were also seen between bone mineral density (BMD) and renal function [ 38 ].…”

“…In a cross-sectional study involving 99 patients with AAV treated with corticosteroids and cyclophosphamide, 78% of patients were found to have abnormal dual-energy X-ray absorptiometry (DEXA) measurements in one of three sites (the lumbar spine, proximal femur or radius); 21% of these patients had osteoporosis and 57% osteopenia [ 38 ]. Cumulative dosage of corticosteroid therapy was inversely related to Z-score; significant correlations were also seen between bone mineral density (BMD) and renal function [ 38 ]. Current UK guidelines developed by the National Osteoporosis Guideline Group (NOGG) advise assessment with FRAX® tool for all patients identified to be at risk of osteoporosis, to help guide further investigations and treatment.…”

Limitations of Standard Immunosuppressive Treatment in ANCA-Associated Vasculitis and Lupus Nephritis

“…Osteopenia was present in at least one place in 57% and osteoporosis in 21% of patients with AAV, with a higher overall prevalence of bone disease in postmenopausal women with AAV [56]. Fractures were described to occur in other studies in 1.5-2.5% of patients with AAV [57].…”

“…Fractures were described to occur in other studies in 1.5-2.5% of patients with AAV [57]. Cumulative dose of corticosteroids, renal impairment, and low BMI were predictors of reduced bone mass [56]. Corticosteroids negatively impact the trabecular bone and predispose to vertebral, rib, and pelvic fractures; the risk of fractures is related to the daily dose of corticosteroids [58], and the loss of bone is highest at the beginning of the treatment when the doses used are the highest.…”