Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease characterized by the presence of chronic destructive synovitis and pathologic bone remodelling of varying degree, ranging from localised articular erosions to juxtarticular osteoporosis, up to systemic osteoporosis (OP). Besides the traditional hypothesis of bone loss as a direct consequence of inflammation, recent studies have demonstrated the role of autoimmunity in the development of bone loss by activation of osteoclasts directly or indirectly by means of autoantibodies. Among the autoantibodies, both rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) appear to play a role in mediating the development of articular erosions at least in part independently from disease activity If solid scientific evidence has confirmed the involvement of RF and ACPAs in the pathogenesis of articular bone loss, a growing number of studies now supports the hypothesis of these autoantibodies also playing a role in the development of systemic OP in RA, which until recently was only believed to be caused by risk factors associated to the disease, such as chronic inflammation and steroid therapy. A paper published by Bugatti et al. in 2016 has evaluated the role of ACPAs and RF on the systemic bone mineral density (BMD) of 155 patients with RA of recent onset, in whom the role of autoantibodies on BMD could be therefore evaluated without the interference of the steroid therapy and the chronic inflammatory state typically associated to RA. The study showed that ACPA positive patients have lower vertebral BMD than ACPA negative patients and that high titers (>100 U/ml) are related to a further decrease in BMD. A significant decrease in femoral BMD was observed only with higher titers of ACPA (>100 U/mL). Concomitant presence of ACPAs and high titers of RFs in the patients? serum was associated to an even greater risk of bone loss, supporting the previously suggested theory that RF may behave as a risk amplifier for ACPA mediated bone loss. The aim of our current study was to evaluate whether autoantibodies play a role in mediating bone loss in RA in the medium term and whether the detrimental effects of autoantibodies on bone health could be reversed by effective therapy, by comparing densitometric values obtained shortly after diagnosis of RA with densitometric values obtained after an interval of 24 months from the first densitometric evaluation. Known risk factors for OP (such as menopause, steroid therapy, disease activity, etc) were recorded and evaluated in a multivariate analysis in order to accurately characterise the role of ACPAs and RF in bone loss in patients with a new diagnosis of RA and after a median period of 24 months. Results from this preliminary study offer important information for the optimal management of patients with RA. In order to prevent systemic bone loss and development of OP, RA patients need to be treated according to the current principles of treat to target and tight control, and association of low doses of prednisone do not impact on BMD in this phase of the disease. Also, any strategy should take into account also screening programs for the assessment of BMD and preventive therapies according to the optimal prescription of bisphosphonates in chronic glucocorticoid users. However, some intrinsic disease characteristics remain associated with increased risk of systemic bone damage despite optimal control of inflammation. In this context, autoantibody positivity, particularly for ACPA, continues to impact on systemic BMD over and above modifiable risk factors. ACPA-positive patients should be thus strictly monitored for the development of OP during their disease course, even in the absence of joint and systemic inflammation.
Impatto degli autoanticorpi anti-citrullina sulla densità minerale ossea sistemica in pazienti con artrite reumatoide precoce. Analisi longitudinale di una coorte iniziale trattata secondo le raccomandazioni internazionali
Impact of anti-citrullinated protein autoantibodies on systemic bone mineral density in patients with early rheumatoid arthritis. Longitudinal analysis of an inception cohort treated according to the international recommendations
DI LERNIA, MICHELE
2018/2019
Abstract
Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease characterized by the presence of chronic destructive synovitis and pathologic bone remodelling of varying degree, ranging from localised articular erosions to juxtarticular osteoporosis, up to systemic osteoporosis (OP). Besides the traditional hypothesis of bone loss as a direct consequence of inflammation, recent studies have demonstrated the role of autoimmunity in the development of bone loss by activation of osteoclasts directly or indirectly by means of autoantibodies. Among the autoantibodies, both rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) appear to play a role in mediating the development of articular erosions at least in part independently from disease activity If solid scientific evidence has confirmed the involvement of RF and ACPAs in the pathogenesis of articular bone loss, a growing number of studies now supports the hypothesis of these autoantibodies also playing a role in the development of systemic OP in RA, which until recently was only believed to be caused by risk factors associated to the disease, such as chronic inflammation and steroid therapy. A paper published by Bugatti et al. in 2016 has evaluated the role of ACPAs and RF on the systemic bone mineral density (BMD) of 155 patients with RA of recent onset, in whom the role of autoantibodies on BMD could be therefore evaluated without the interference of the steroid therapy and the chronic inflammatory state typically associated to RA. The study showed that ACPA positive patients have lower vertebral BMD than ACPA negative patients and that high titers (>100 U/ml) are related to a further decrease in BMD. A significant decrease in femoral BMD was observed only with higher titers of ACPA (>100 U/mL). Concomitant presence of ACPAs and high titers of RFs in the patients? serum was associated to an even greater risk of bone loss, supporting the previously suggested theory that RF may behave as a risk amplifier for ACPA mediated bone loss. The aim of our current study was to evaluate whether autoantibodies play a role in mediating bone loss in RA in the medium term and whether the detrimental effects of autoantibodies on bone health could be reversed by effective therapy, by comparing densitometric values obtained shortly after diagnosis of RA with densitometric values obtained after an interval of 24 months from the first densitometric evaluation. Known risk factors for OP (such as menopause, steroid therapy, disease activity, etc) were recorded and evaluated in a multivariate analysis in order to accurately characterise the role of ACPAs and RF in bone loss in patients with a new diagnosis of RA and after a median period of 24 months. Results from this preliminary study offer important information for the optimal management of patients with RA. In order to prevent systemic bone loss and development of OP, RA patients need to be treated according to the current principles of treat to target and tight control, and association of low doses of prednisone do not impact on BMD in this phase of the disease. Also, any strategy should take into account also screening programs for the assessment of BMD and preventive therapies according to the optimal prescription of bisphosphonates in chronic glucocorticoid users. However, some intrinsic disease characteristics remain associated with increased risk of systemic bone damage despite optimal control of inflammation. In this context, autoantibody positivity, particularly for ACPA, continues to impact on systemic BMD over and above modifiable risk factors. ACPA-positive patients should be thus strictly monitored for the development of OP during their disease course, even in the absence of joint and systemic inflammation.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/24360