Hepatocyte growth factor is a predictor of development of new syndesmophytes in men with ankylosing spondylitis. A five year prospective study

• Background: Patients with ankylosing spondylitis (AS) have an increased risk of spinal new bone formation characterized by the development of syndesmophytes. Knowledge of predictors for development of syndesmophytes is limited. Hepatocyte growth factor (HGF) has regulatory effects on a variety of cells in many different organs. HGF signaling can affect both osteoclast and osteoblast lineages and has been shown to promote osteogenesis. Cross-sectional association between increased HGF and increased modified Stoke Ankylosing Spine Score (mSASSS) has previously been shown [1], whereas knowledge of HGF as a predictor for new bone formation is lacking.Objectives: To study serum HGF as a predictor for development of new syndesmophytes in patients with AS followed for five years.Methods: Serum levels of HGF was analyzed using ELISA in patients with AS (modified NY-criteria) and in healthy controls (HC) at baseline. Spinal lateral radiographs were obtained at baseline and at the 5-year follow-up and assessed for development of new syndesmophytes using mSASSS. Univariate and multivariable logistic regression analyses were used to assess predictors for development of ≥ 1 new syndesmophyte.Results: Serum HGF and radiographs at baseline and follow-up were available for 163 patients, 88 men and 75 women, baseline mean age 50±12 years. AS patients had higher serum HGF than HC (n=80), p=0.050. In the AS group, 36 patients (22%) developed ≥ 1 syndesmophyte, 27 men and 9 women. In the total AS group, neither did baseline serum HGF differ between those who developed ≥ 1 new syndesmophyte and those who did not progress, nor did it predict development of ≥ 1 new syndesmophyte in the univariate analysis, p=0.25. Interestingly, men who developed ≥1 new syndesmophyte had higher serum HGF than the non-progressors (1706±454 vs 1420±338 pg/mL, p=0.001) and increased serum HGF at baseline predicted development of ≥ 1 syndesmophyte (OR per 1 SD HGF 2.39, 95% CI 1.31 to 4.36) in the univariate analysis. Serum HGF did not predict new syndesmophytes in women, p=0.13. Multivariable analysis for men including age, smoking, baseline syndesmophyte and serum HGF showed high HGF (OR per 1SD 1.90, 95% CI 1.01 to 3.59) and ≥1 baseline syndesmophyte (OR 3.48, 95% CI 1.09 to 11.07) to independently predict development of ≥ 1 new syndesmophyte. If baseline CRP was included in the multivariable model, serum HGF and baseline syndesmophytes remained the significant predictors.Conclusion: High baseline serum HGF was shown to independently predict the development of at least one new syndesmophyte over five years in men with AS.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

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