Insight on Bone Morphogenetic Protein 7 in Ankylosing Spondylitis and its association with disease activity and radiographic damage

Abstract

Introduction: Fusion of joints as well as intervertebral spaces by the formation of bony spurs appearing as syndesmophytes and osteophytes are the hallmark of spondyloarthropathies which accounts for disability. The aim of this study was to assess the serum level of bone morphogenetic protein (BMP)-7 in ankylosing spondylitis and its relationship with disease activity and the radiographic damage.

Methods: This longitudinal case control study was conducted in Ain Shams University Hospitals (Egypt). A total of 55 subjects were included in two case groups and one control group. Group I included 20 patients with Ankylosing Spondylitis (AS) assessed at baseline (defined as Ia and after 18 months defined as Ib). Group II included 20 patients with Rheumatoid Arthritis (RA) and Group III included 15 healthy subjects as controls. Patients with other forms of seronegative spondyloarthropathies, bone forming diseases were excluded from the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI) were used to assess disease activity in AS patients. RA disease activity was assessed using the disease activity score 28 (DAS28). Radiographic changes were assessed using the Bath AS Radiographic Index (BASRI) in AS and Larsen scores in RA. Laboratory investigations included: Complete blood picture (CBC), Erythrocyte sedimentation rate (ESR), quantitative CRP, serum calcium, phosphorus and alkaline phosphatase. Determination of serum bone morphogenetic protein-7 level (BMP-7) was done using enzyme linked immunosorbent assay (ELISA). Sample collections, clinical and radiological assessments were performed at baseline for all groups and after a mean follow-up of 18 months for Group I. Data were analyzed by SPSS 17, using t-test, Kruskal-Wallis, Mann-Whitney, Fischer exact test, Chi square, and Pearson Product-Moment Correlation Coefficient.

Results: There were statistically significant differences between the 3 groups as regard baseline BMP-7 levels; the mean BMP-7 level of AS patients was significantly higher than that of RA patients and controls and significantly higher in the RA group than that of controls. BMP-7 levels were not associated with any of the clinical or drug related variables either in AS or RA. In AS BMP-7 levels showed significant increase after follow up and significant positive correlation with serum alkaline phosphatase (both at baseline and after follow up) and BASDAI score (after follow up) respectively. Despite the parallel increase of BMP7 and BASRI score during the follow-up period no statistically significant correlation was detected. There were no significant correlations between BMP7 level and patient’s age or any disease related characteristics in the RA group.

Conclusion: A significant progressive increase in serum BMP-7 was noted in AS patients that correlated with serum markers of bone formation. Such a biomarker measurement may not only act as a surrogate marker for the disease but has the potential to contribute to the pathogenesis of AS that may provide a complementary or alternative therapeutic approach.