***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: We have genotyped 14,436 nonsynonymous SNPs ( nsSNPs ) and 897 major histocompatibility complex ( MHC ) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS ) , autoimmune thyroid disease ( AITD ) , multiple sclerosis ( MS ) and breast cancer ( BC ) . Comparing these data against a common control data set derived from 1,500 r and omly selected healthy British individuals , we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis , ARTS1 and IL23R , and confirmation of the previously reported association of AITD with TSHR and FCRL3 . These findings , enabled in part by increased statistical power result ing from the expansion of the control reference group to include individuals from the other disease groups , highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major ' seronegative ' diseases Objective . Ankylosing spondylitis ( AS ) is characterized by chronic inflammation leading to ankylosis , but also to low bone mineral density ( BMD ) and vertebral fractures ( VFx ) . Treatment with tumor necrosis factor-α blockers decreases inflammation and has shown to be effective in increasing BMD . We studied the effects of etanercept ( ETN ) on BMD and VFx in patients with AS after 2 years of treatment . Further , we studied changes in bone turnover markers and radiological damage . Methods . Patients with active AS , treated with ETN for 2 years , were included . BMD lumbar spine and hip were measured at baseline and after 2 years , as well as radiological damage ( modified Stoke Ankylosing Spondylitis Spinal Score with the addition of the thoracic spine ) , VFx ( Genant method ) , and change in bone turnover markers . Results . Forty-nine patients with AS were included . After 2 years of ETN , hip BMD increased by 2.2 % ( p = 0.014 ) and lumbar spine BMD by 7.0 % ( p < 0.001 ) . The Bath Ankylosing Spondylitis Disease Activity Index decreased significantly ( p < 0.001 ) , as well as C-reactive protein and erythrocyte sedimentation rate ( p < 0.001 ) . Despite ETN therapy , the number of patients with VFx more than doubled ( from 6 to 15 patients , p = 0.003 ) . Also , the radiological damage increased significantly over time ( from 12.1 to 18.5 , p < 0.001 ) ; however , no significant change in bone turnover markers was found . Conclusion . This prospect i ve longitudinal observational cohort study showed that after 2 years of ETN , BMD of the hip and spine increased significantly , but the number of patients with VFx and the severity of VFx increased as well . Besides that , radiological progression , including the thoracic spine , increased significantly . Thus , the favorable bone-preserving effect is accompanied by unfavorable outcomes on VFx and radiological damage OBJECTIVE To determine the changes in body weight , body composition , and bone density in patients with spondyloarthropathy ( SpA ) receiving anti-tumor necrosis factor-alpha ( TNF-alpha ) treatment . METHODS One hundred six patients with SpA ( 80 men , 26 women ) aged 20 - 71 years were included in a 2-year prospect i ve open study . Fifty-nine patients received infliximab ( 3 or 5 mg/kg/infusion each 6 or 8 weeks ) ; and 47 patients received etanercept ( 25 mg twice a week ) because of persistent active disease despite an optimal treatment , according to ASsessment s in Ankylosing Spondylitis Working Group criteria . Body weight , total body composition ( lean mass , fat mass ) , and spine and femoral bone mineral density ( BMD ; dual-energy x-ray absorptiometry ) were measured at baseline and at 1 and 2 years . RESULTS There was a significant increase in body weight after 1 year ( 2.2 + /- 3.9 kg , i.e. , 3.4 % ; p < 0.0001 ) and 2 years ( 2.2 + /- 4.7 kg , 3.5 % ; p < 0.0001 ) , mostly due to a significant gain in fat mass at 1 year ( 1.4 + /- 2.6 kg , 12.1 % ; p < 0.0001 ) and 2 years ( 1.5 + /- 3.1 kg , 14.5 % , p < 0.0001 ) . Gain in lean mass was also significant at 1 year ( 0.8 + /- 2.2 kg , 1.9 % ; p < 0.0001 ) and 2 years ( 0.9 + /- 2.5 kg , 2 % ; p < 0.0001 ) . At 2 years , lumbar spine and femur BMD increased : + 5.8 + /- 13 % ( p < 0.0001 ) and + 2.26 + /- 4.5 % ( p = 0.001 ) , respectively . CONCLUSION This 2-year prospect i ve study showed a significant increase in body weight at 1 year and 2 years , mostly due to a gain in fat mass and a significant increase in BMD , in patients with SpA receiving anti-TNF-alpha treatment BACKGROUND Ankylosing spondylitis is a chronic immune-mediated inflammatory disease characterised by spinal inflammation , progressive spinal rigidity , and peripheral arthritis . Interleukin 17 ( IL-17 ) is thought to be a key inflammatory cytokine in the development of ankylosing spondylitis , the prototypical form of spondyloarthritis . We assessed the efficacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis . METHODS We did a r and omised double-blind proof-of-concept study at eight centres in Europe ( four in Germany , two in the Netherl and s , and two in the UK ) . Patients aged 18 - 65 years were r and omly assigned ( in a 4:1 ratio ) to either intravenous secukinumab ( 2 × 10 mg/kg ) or placebo , given 3 weeks apart . R and omisation was done with a computer-generated block r and omisation list without a stratification process . The primary efficacy endpoint was the percentage of patients with a 20 % response according to the Assessment of SpondyloArthritis international Society criteria for improvement ( ASAS20 ) at week 6 ( Bayesian analysis ) . Safety was assessed up to week 28 . This study is registered with Clinical Trials.gov , number NCT00809159 . FINDINGS 37 patients with moderate-to-severe ankylosing spondylitis were screened , and 30 were r and omly assigned to receive either intravenous secukinumab ( n=24 ) or placebo ( n=6 ) . The final efficacy analysis included 23 patients  receiving secukinumab and six patients receiving placebo , and the safety analysis included all 30 patients . At week 6 , ASAS20 response estimates were 59 % on secukinumab versus 24 % on placebo ( 99·8 % probability that secukinumab is superior to placebo ) . One serious adverse event ( subcutaneous abscess caused by Staphylococcus aureus ) occurred in the secukinumab-treated group . INTERPRETATION Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated . It is the first targeted therapy that we know of that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial . FUNDING Novartis Introduction The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha ( TNF-α ) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers ( BTM ) for treatment discontinuation in patients with ankylosing spondylitis ( AS ) . Methods This is a prospect i ve cohort study of 111 consecutive AS out patients who started TNF-α blocking therapy .  Clinical assessment s and BTM were assessed at baseline , three and six months , as well as at one , two , and three years . Z-scores of BTM were calculated to correct for age and gender . Bone mineral density ( BMD ) was assessed yearly . Results After three years , 72 patients ( 65 % ) were still using their first TNF-α blocking agent . In these patients , TNF-α blocking therapy result ed in significantly increased bone-specific alkaline phosphatase , a marker of bone formation ; decreased serum collagen-telopeptide ( sCTX ) , a marker of bone resorption ; and increased lumbar spine and hip BMD compared to baseline . Baseline to three months decrease in sCTX Z-score ( HR : 0.394 , 95 % CI : 0.263 to 0.591 ) , AS disease activity score ( ASDAS ; HR : 0.488 , 95 % CI : 0.317 to 0.752 ) , and physician 's global disease activity ( HR : 0.739 , 95 % CI : 0.600 to 0.909 ) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance . Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity , physical function and quality of life . Conclusions Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation , especially mineralization , in combination with continuous improvement of lumbar spine BMD . Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS , in addition to the currently used more subjective measures OBJECTIVE To study the effect of tumor necrosis factor α ( TNFα ) inhibitors on  progressive spinal damage in patients with ankylosing spondylitis ( AS ) . METHODS All AS patients meeting the modified New York criteria who had been monitored prospect ively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study ( n=334 ) . The patients received st and ard therapy , which included nonsteroidal antiinflammatory drugs and TNFα inhibitors . Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors . Univariable and multivariable regression analyses were done . Propensity score matching and sensitivity analysis were performed . A zero-inflated negative binomial ( ZINB ) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods . Potential confounders , such as disease activity ( as assessed by the Bath Ankylosing Spondylitis Disease Activity Index ) , the erythrocyte sedimentation rate , C-reactive protein level , HLA-B27 positivity , sex , age at onset , smoking burden ( number of pack-years ) , and baseline damage , were included in the model . RESULTS TNFα inhibitor treatment was associated with a 50 % reduction in the odds of progression , with an odds ratio ( OR ) of 0.52 ( 95 % confidence interval [ 95 % CI ] 0.30 - 0.88 , P=0.02 ) . Patients with a delay of > 10 years in starting therapy were more likely to experience progression as compared to those who started earlier ( OR 2.4 [ 95 % CI 1.09 - 5.3 ] , P=0.03 ) . In the ZINB model , the use of TNFα inhibitors  significantly reduced disease progression when the gap between radiographs was > 3.9 years . The protective effect of TNFα inhibitors was stronger after propensity score matching . CONCLUSION Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients , especially with early initiation and with longer duration of followup Objective . To evaluate the effect of anti-tumor necrosis factor ( TNF ) therapy on bone mineral density ( BMD ) in patients with active ankylosing spondylitis ( AS ) with low BMD . Methods . Eighty-nine patients with active AS with low BMD were r and omly divided into either a study group or a control group . The study group received etanercept ( 50 mg/week ) or adalimumab ( 40 mg/2 week ) subcutaneously for 1 year . BMD of lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry , and bone turnover markers serum C telopeptide of type-I collagen ( sCTX ) and serum procollagen type-I N propeptide ( PINP ) were detected by ELISA at baseline and at end of study . Results . After 1 year , compared with baseline , there was a significant increase in spine and femoral neck BMD by a mean ± SD of 14.9 % ± 15.6 % ( p < 0.0001 ) and 4.7 % ± 7.9 % ( p < 0.0001 ) in the study group . In the control group , there was a significant decrease in spine and femoral neck BMD by a mean ± SD of −8.6 % ± 9.7 % ( p < 0.0001 ) and −9 
    Output:
    
Summary TNFi therapy improves bone density but not vertebral fracture rates .
Secukinumab improves symptoms and may slow radiographic progression .
Data is lacking regarding the effects of secukinumab on BMD and fractures .