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Abstract
Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by both excessive bone formation and bone loss. The bone turnover marker (BTM) bone-specific alkaline phosphatase (BALP) plays a central role in bone mineralization. Our previous study demonstrated that 3 years of TNF-α blocking therapy results in a significant increase in BALP.1 However, longer follow-up is needed to investigate whether BALP stays elevated during TNF-α blocking therapy and also to explore the course of other BTM, osteocalcin (OC), procollagen type 1 N-terminal peptide (PINP) and serum type 1 collagen C-telopeptide (sCTX) in AS.
Objectives: To evaluate serum markers of bone resorption, formation, and mineralization during 8 years of TNF-α blocking therapy in AS patients.
Methods: Included were consecutive AS outpatients from the University Medical Center Groningen (UMCG) attending the Groningen-Leeuwarden Axial SpA (GLAS) cohort and who were treated with a maximum of 2 TNF-α blockers for at least 8 years. Patients were excluded when they used bisphosphonates at baseline or during follow-up. Data for a specific visit was coded as missing when patients either had experienced a fracture or received systemic corticosteroids within 1 year of that particular visit. Clinical and laboratory measurements were performed at baseline (before start of TNF-α blocking therapy), 3 and 6 months as well as 1, 2, 4, 6 and 8 years. Markers of bone formation OC, PINP and BALP, and marker of bone resorption sCTX were measured in serum. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group to correct for the normal influence that age and gender have on bone turnover. Serum levels of 25-hydroxyvitamin D (25(OH)D3) were assessed yearly. Generalized estimating equations were used to analyze BTM Z-scores over time within patients. Simple contrast was used to compare follow-up visits to baseline. P-values <0.05 were considered statistically significant.
Results: In total, 37 AS patients were analyzed; 62% were male, 86% HLA-B27+, mean age was 38.6 ± 10.4 years, median symptom duration 14 years (IQR 10-25), median CRP 13 mg/L (IQR 6-25), and 30% had low vitamin 25(OH)D3 status (<50) at baseline. 35% of patients switched to a second TNF-α inhibitor during follow-up. ASDASCRP improved significantly during treatment, from mean 3.8 ± 0.9 at baseline to 1.9 ± 0.9 after 8 years of follow-up (P<0.001). 25(OH)D3 levels were stable at group level, median 58 nmol/L (IQR 45-70) at baseline and 60 nmol/L (IQR 50-70) after 8 years. Bone regulation marker OC Z-score was found to be significantly increased only after 3 months of TNF-α blocking therapy compared to baseline. No significant changes during follow-up were found for collagen resorption marker sCTX Z-score. Collagen formation marker PINP Z-score was significantly increased after 3 and 6 months as well as 2 years of TNF-α blocking therapy. Bone mineralization marker BALP Z-score was significantly increased at all time points up to and including 2 years and returned to baseline levels during 4 to 8 years of TNF-α blocking therapy (Figure 1).
Conclusion: In this subgroup of AS patients with established and active disease responding to TNF-α blocking therapy, we observed that the bone turnover balance favored bone formation during the first years of TNF-α blocking therapy, which corresponds to previously reported improvement in bone mineral density, especially at the lumbar spine.1 New finding of our study is that after 8 years of treatment, markers of bone resorption, formation, and mineralization were all comparable to baseline values.
References: [1]Arends et al. Arthritis Res Ther. 2012;14(2):R98
Disclosure of Interests: : Mark Siderius: None declared, Anneke Spoorenberg: None declared, Suzanne Arends Grant/research support from: Grant/research support from Pfizer