Influence of anti-TNF alpha treatment in bone metabolism markers

Abstract

Chronic inflammatory joint diseases are a heterogeneous group of disorders associated with local and systemic bone loss. Tumor necrosis factor alpha (TNFα), a pivotal proinflammatory cytokine common in the pathogenesis of these diseases, is known to induce bone loss by increasing osteoclast recruitment and activity. Anti-TNFα antibodies used in the treatment of inflammatory arthropaties may influence the risk of osteoporosis, by preventing bone loss. The exact mechanism of preventing bone loss has not yet clearly assessed. The main purpose of this work was to examine the fluctuation of biochemical markers of bone metabolism induced by three different anti-TNF agents (Infliximab, Etanercept and Adalimumab), taking into account their different pharmacokinetic profiles. We evaluate patients with inflammatory rheumatic diseases treated with biologics. Data on demographic characteristics, pharmacological treatment history, anti-TNF treatment duration and disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI, Disease activity score for 28 joints, DAS28) were collected. Blood and urine samples were collected in the day of drug administration (day A), immediately before administration and in the estimated day of maximum plasmatic level of each drug (day I). We determined, by ELISA, serum bone-specific alkaline phosphatase (sBAP), serum osteocalcin (sOC) and urine deoxipyridinoline (uDPD) using creatinin (Cr) as a normalization factor for urine samples. Changes between days were analyzed by Paired sample T test. Statistical significance was assumed for p values <0.05. These study enrolled 58 patients (67,2% females); 35 with rheumatoid arthritis (RA) (DAS28=3.8±1.4), 17 with ankylosing spondylitis (AS) (BASDAI=3.4±2.3) and 6 with psoriatic arthritis (PsA) (DAS28=3.1±1.1), with a mean age 48,9±14 years. The average biological treatment duration was 25±16 months. Changes in biological parameters from baseline (day A) to day I were calculate and also presented graphically. We also performed ratios between formation and resorption markers (sOC/uDPDcr and sOC/uDPDcr). Our study showed an oscillation towards a decrease of DPDCr, a bone resorption marker, between the day of minimum and maximum anti-TNFα antibodies plasmatic levels mainly for infliximab and etenercept groups. Contrariwise bone formation markers (OC and BAP) showed no statistical significant changes with an exception for sBAP for the Adalimumab group. The positive change on ratio bone formation/resorption markers lead to a net bone formation, which suggest that anti-TNFα antibodies prevent osteoporosis. Further research is warranted to clarify whether fluctuations and differences are reflected in the actual osteoporosis risk in these patients.