L Osteoporosi nelle Spondiloartriti Prof Maurizio Rossini UOC Reumatologia Università di Verona
Densità minerale ossea in pazienti con artrite psoriasica g/cm² 1,4 1,2 Maschi P< 0.01 P< 0.01 P< 0.05 Controlli Pz g/cm² 1,4 1,2 Donne premenopausali P< 0.01 1 1 P< 0.05 0,8 0,8 0,6 0,6 0,4 g/cm² 1,4 T. Body Lumbar Neck Donne postmenopausali 0,4 g/cm² 1,4 T. Body Lumbar Neck Tutti i pazienti P< 0.01 1,2 P< 0.01 P< 0.01 1,2 P< 0.01 1 P< 0.01 1 P< 0.05 0,8 0,8 0,6 0,6 0,4 T. Body Lumbar Neck 0,4 T. Body Lumbar Neck Frediani B et al, J Rheumatol 2001
Comparison of frequency of Osteoporosis in PSA Busquets et al, Rheumatol Clin 2014
Markers of inflammation correlate with bone resorption in PsA Grisar J, J Rheumatol, 2002
PsA: the duration of arthritis Borman P et al, Clin Rheumatol, 2008
High prevalence of low BMD in patients within 10 years of onset of ankylosing spondylitis Prevalenza di Osteoporosi in pz di 35 anni in media, prevalentemente maschi = 16% colonna, 13% femore Van der Weijden et al, Clin Rheum 2012
Proportion with low BMD (Tscore<-2) in patients with symptoms suggestive of SPA Forien et al, Osteoporos Int 2015
SA e BMD: effetti della gravità e dell attività di malattia 1 Colonna Femore 0 0 Z-score -1-2 Severità 4 o > 2-3.9 0-1.9 Test di Schober Variazione % BMD -1-2 -3-4 -5-6 Attiva Inattiva Donnelly S et al, Ann Rheum Dis 1994 Gratacos et al, Arthritis Rheum 1999
The BMD measurement at the lateral lumbar spine reflects bone loss and fracture risk better than posteroanterior spine Ulu et al, Rheumatol Int, 2013
Scatter plots of msasss and BMD measured at different locations Klingberg et al, Arth Res Ther, 2012
High-resolution peripheral quantitative computed tomography: bone microarchitecture in AS AS vs Controls: Lower cortical vbmd in radius Lower trabecular vbmd in tibia AS with vertebral fractures vs AS: Lower cortical vbmd in lumbar spine Lower cortical cross-sectional area in radius and tibia Thinner cortical bone in radius and tibia msasss correlated negatively with trabecular vbmd and thickness in lumbar spine, radius and tibia Syndesmophytes were significantly associated with decreasing trabecular vbmd but increasing cortical vbmd in lumbar spine Bone loss is general, whereas osteoproliferation is local! Klingberg et al, Arth Res Ther, 2013
SPONDILITE ANCHILOSANTE E RISCHIO DI FRATTURE 3,5 * 3,26 3 2,5 Relative risk 2 1,5 1 0,5 1,02 1,21 0,77 0 Any fracture Radius/ulna Hip Vertebral Vosse D et al, ARD, 2009
Prieto-Alhambra et al, Osteoporos Int, 2014
Ankylosing Spondylitis is Associated with an Increased Risk of Vertebral and Non-Vertebral Clinical Fractures: A Population-Based Cohort Study 6474 SA vs 32346 controls HR = 1,93 HR = 1,19 Munoz-Ortego et al, JBMR, 2014
Kang etal, Arth Res Ther, 2014
Prevalence of vertebral fractures in AS Sambrook et al, Ther Adv Musculoskel Dis, 2012
Known Risk factors associated with vertebral fracture in AS: 1. lower BMD in both the central and peripheral skeleton, 2. advanced age, 3. male sex, 4. longstanding disease, 5. impaired back mobility, 6. increased occiput-to-wall distance 7. syndesmophyte formation or msasss, 8. disease activity, 9. peripheral joint involvement Sambrook et al, Ther Adv MS Dis, 2012
Predictors of vertebral fractures in AS Kang etal, Arth Res Ther, 2014
Sede delle fratture vertebrali nella SA 70 % dei pazienti fratturati 60 50 40 30 20 10 0 Altre D D10 D11 D12 L Rossini et al, EULAR, ARD, 2013
modified Stoke Ankylosing Spondylitis Spine Score (msasss) per vertebra in women and men Klingberg et al, Arth Res Ther, 2012
Biomechanical changes Unusual characteristics of vertebral fractures: cervical location posterior arch involvement extension fractures neurological complications
Increased occurrence of spinal fractures related to AS in Sweden Pts 729 1226 Robinson et al, Pat Saf Serg 2013
Hyperextension fracture in ankylosing spinal disorders Westerveld et al, Spine J, 2013
Caratteristiche Morfometriche delle Fratture Rossini et al, Reumatismo, 2006
DXA IMAGING in AS Rossini et al, Reumatismo, 2006
Aubry-Rozier et al, J Clin Dens, 2014
Bone Formation in AS!
Rossini et al, Calcif Tissue Int, 2013 Via Wnt/β-catenina e i suoi inibitori DKK1:Dikkopf-1 SOST: Sclerostina
+++ ++ Role of DKK1 in the regulation of bone formation in pathological conditions DISH AS + Bone Formation - -- --- RA: Osteoporosis and bone erosions Multiple Myeloma --- -- - DKK1 + ++ +++ Rossini M et al, CTI, 2013
High level of DKK1 predicts protection from syndesmophyte formation Heiland et al, ARD, 2012
Altered skeletal expression of sclerostin and its link to radiographic progression in AS Appel et al Arthritis Rheum 2009
Sclerostin levels and Inflammation Saad et al, Arth Res Ther, 2012
Perché Osteoporosi nella SA? 1. Infiammazione sistemica e citochine proinfiammatorie (TNF, IL1, IL6) con effetti negativi sul metabolismo osseo. (Korczowska et al 2011) 2. Ridotta mobilità per dolore e rigidità. (Will et al. 1989) 3. Fattori biomeccanici legati alla ridistribuzione del carico sul corpo vertebrale a causa dell inusuale supporto meccanico extraspinale (legge di Wolff) 4. Malattia infiammatoria intestinale subclinica? (De Keyser 2002, El Maghraoui 1999) by Rossini
Molecular mechanisms of bone resorption in AS Davey-Ranasinghe et al, Curr Opin Rheumatol, 2013
Bone Turnover Markers in AS Coiffier et al, Joint Bone Spine, 2013
EFFECTS of TNF Schett, Ann Rheum Dis, 2010
The effect of TNF alpha blocking therapy on BTM Arends et al, Arth Res Ther 2012
The effect of TNF alpha blocking therapy on BMD Arends et al, Arth Res Ther 2012
Meta-Analysis of Tumor Necrosis Factor Inhibitors on Bone Density in Ankylosing Spondylitis Trials Siu et al, Arthitis Care Res, 2015
The TNF brake hypothesis Maksymowich Nar Rev Rheum, 2010
Effects on bone related outcome of TNF-alfa blocking therapy in AS Arends et al, Curr Opin Rheumatol 2014
Systematic review of association between vitamin D levels and disease activity of ankylosing spondylitis Zhao et al, Rheumat, 2014, modif by Rossini
Nuova Nota 79 AIFA