Background/Purpose

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation that progressively leads to ankylosis and functional disability. The mechanisms of new bone formation in AS are yet to be characterized. Several biomarkers are involved in bone remodeling in AS, such as Dickkopf-1 (Dkk-1) and sclerostin, which down-regulate bone formation by inhibition of Wingless proteins (Wnt) and bone morphogenic proteins (BMPs). Wnt and BMPs are key inducers of osteoblastogenesis and new bone formation. The aim of this study was to determine serum concentrations of BMP7, Dkk-1 and sclerostin in patients with AS and to investigate their relationship to clinical manifestations and structural damage.

Methods

Serum levels of BMP-7, DKK-1, Sclerostin were detected by enzyme-linked immunosorbent assay in 40 AS patients with syndesmophyte (male: 36, female: 4, age: 32.43±7.63), 40 AS patients without syndesmophyte (male: 35, female: 5, age: 29.8±7.18) and 23 healthy controls (male: 32, female: 8, age: 31.95±9.42). Clinical manifestations such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score and Bath Ankylosing Spondylitis Functional Index (BASFI) score were evaluated in AS patients. Cervical and lumbar spine x-rays were performed in 80 patients to measure modified Stoke’s Ankylosing Spondylitis Spine Score (mSASSS). SPSS17.0 was performed to analyze statistical difference. P-values less than 0.05 were considered statistically significant.

Results

Serum level of BMP-7 in AS patients with and without syndesmophyte（74.39±49.53 pg/ml, 89.17±83.31 pg/ml） was significantly higher than healthy control group (40.30±16.19 pg/ml, P=0.001, P=0.002）. Sclerostin level in AS patients with and without syndesmophyte（184.46±316.08 pg/ml,187.79±223.53 pg/ml） was significantly higher than healthy control group（87.40±34.28 pg/ml, P=0.044, P=0.002）. There was no significant differences of BMP-7 and sclerostin level in AS patients with or without syndesmophyte. No significant differences of DKK-1 level had been found in AS patients with (1174.29±863.90 pg/ml) or without syndesmophyte (971.44±677.9 pg/ml) and control group (1090.05±809.75 pg/ml). Serum DKK-1 level in AS patients was positively correlated with ESR (P=0.029). However, no biomarkers showed significant correlation with age, sex, course of disease, sacroiliitis grade, BASDAI, BASFI and structural damage (mSASSS). Furthermore, there was no correlation between three biomarkers. 

Conclusion

Both osteoinductive factor BMP-7 and its inhibitor sclerostin increased in AS patients. This may reflect a counter-balancing mechanism in AS new bone formation leading to bone remodeling.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-levels-of-bone-morphogenetic-protein-7-and-sclerostin-are-elevated-in-ankylosing-spondylitis-but-not-linked-with-structural-damage/