Increased serum fibroblast growth factor-23 and decreased bone turnover in patients with systemic lupus erythematosus under treatment with cyclosporine and steroid but not steroid only.

ABSTRACT

SUMMARY: In patients with systemic lupus erythematosus (SLE), low bone mineral density (BMD) is associated with increased age, prolonged disease, low body mass index (BMI), and overlap with rheumatoid arthritis (RA). Elevated fibroblast growth factor (FGF)-23 in cyclosporine A (CsA) users with SLE are associated with decreased active vitamin D and osteocalcin. INTRODUCTION: The objective of this study was to investigate the steroid and CsA effect on bone metabolism and serum FGF-23 in SLE patients. METHODS: Seventy-two SLE patients and 10 age- and sex-matched healthy individuals underwent blood tests for bone metabolic biomarkers and FGF-23, and lumbar spine dual-energy X-ray absorptiometry for BMD. RESULTS: Comparisons between patients and controls were made in premenopausal women/men younger than 50 years and postmenopausal women/men older than 50 years separately. SLE patients had more frequent low Z-score (≤-2.0, 8.5 vs. 0%), osteopenia (-2.5osteoporosis (T-score≤-2.5, 12 vs. 0%), than the healthy age-compatible counterparts. BMD was significantly lower in patients with advanced age, longer disease duration, lower BMI, and overlap with RA (all p<0.05 by multiple linear regression analyses). Serum FGF-23 was significantly higher and 1,25-dihydroxyvitamin D (1,25(OH)2D3) lower in SLE patients treated with glucocorticoid and CsA than in those not taking both of them (p=0.027 and 0.002, respectively). The cumulative dose of glucocorticoid was inversely correlated with serum intact parathyroid hormone (r=-0.299, p=0.011), C-terminal telopeptide of type I collagen (r=-0.581, p<0.001), and osteocalcin (r=-0.648, p<0.001). FGF-23 and the cumulative dose of CsA were positively correlated (r=0.38, p=0.001) and both were negatively correlated with 1,25(OH)2D3 (r=-0.266, p=0.016 and r=-0.55, p<0.001) and osteocalcin (r=-0.234, p=0.034 and r=-0.274, p=0.02).

CONCLUSION:

SLE patients treated with glucocorticoid and CsA exhibited markedly decreased bone turnover. Those taking CsA had higher serum FGF-23 associated with suppression of 1,25(OH)2D3 and bone formation. Such high-risk patients necessitate regular screening of osteoporosis.