***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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    Input: Objective To determine the prevalence of vertebral fractures ( VFs ) after 5 years of disease activity score (DAS)-steered treatment in patients with early rheumatoid arthritis ( RA ) and to investigate the association of VFs with disease activity , functional ability and bone mineral density ( BMD ) over time . Methods Five-year radiographs of the spine of 275 patients in the BeSt study , a r and omized trial comparing four treatment strategies , were used . Treatment was DAS-steered ( DAS ≤ 2.4 ) . A height reduction > 20 % in one vertebra was defined a vertebral fracture . With linear mixed models , DAS and Health Assessment Question naire ( HAQ ) scores over 5 years were compared for patients with and without VFs . With generalized estimating equations the association between BMD and VFs was determined . Results VFs were observed in 41/275 patients ( 15 % ) . No difference in prevalence was found when stratified for gender , prednisone use and menopausal status . Disease activity over time was higher in patients with VFs , mean difference 0.20 ( 95 % CI : 0.05 - 0.36 ) , and also HAQ scores were higher , independent of disease activity , with a mean difference of 0.12 ( 95 % CI : 0.02 - 0.2 ) . Age was associated with VFs ( OR 1.06 , 95 % CI : 1.02 - 1.09 ) , mean BMD in spine and hip over time were not ( OR 95 % CI , 0.99 : 0.78 - 1.25 and 0.94 : 0.65 - 1.36 , respectively ) . Conclusion After 5 years of DAS-steered treatment , 15 % of these RA patients had VFs . Higher age was associated with the presence of VFs , mean BMD in hip and spine were not . Patients with VFs have greater functional disability over time and a higher disease activity , suggesting that VFs may be prevented by optimal disease activity suppression Summary Serum high-sensitivity C-reactive protein ( CRP ) is an inflammatory biomarker . We investigated the relationship between  CRP and bone health in the Rotterdam Study . Serum high-sensitivity CRP was associated with fracture risk and lower femoral neck bending strength . Mendelian r and omization analyses did not yield evidence for this relationship being causal . Introduction Inflammatory diseases are associated with bone pathology , reflected in a higher fracture risk . Serum high-sensitivity CRP is an inflammatory biomarker . We investigated the relationship between CRP and bone mineral density ( BMD ) , hip bone geometry , and incident fractures in the Rotterdam Study , a prospect i ve population -based cohort . Methods At baseline , serum high-sensitivity CRP was measured . A weighted genetic risk score was compiled for CRP based on published studies ( 29 polymorphisms ; Illumina HumanHap550 Beadchip genotyping and HapMap imputation ) . Regression models were reported per st and ard deviation increase in CRP adjusted for sex , age , and BMI . Complete data was available for 6,386 participants , of whom 1,561 persons sustained a fracture ( mean follow-up , 11.6 years ) . Results CRP was associated with a risk for any type of fracture [ hazard ratio ( HR ) = 1.06 ; 95 % confidence interval ( CI ) , 1.02–1.11 ] , hip fractures ( HR = 1.09 ; 1.02–1.17 ) and vertebral fractures [ odds ratio ( OR ) = 1.34 ; 1.14–1.58 ] . An inverse relationship between CRP levels and section modulus ( −0.011 cm3 ; −0.020 to −0.003 cm3 ) was observed . The combined genetic risk score of CRP single nucleotide polymorphisms ( SNPs ) was associated with serum CRP levels ( p = 9 × 10−56 ) , but not with fracture risk ( HR = 1.00 ; 0.99–1.00 ; p = 0.23 ) . Conclusions Serum high-sensitivity CRP is associated with fracture risk and lower bending strength . Mendelian r and omization analyses did not yield evidence for this relationship being causal . Future studies might reveal what factors truly underlie the relationship between CRP and fracture risk Epidemiological studies have shown low- grade inflammation measured by high-sensitivity C-reactive protein ( hs-CRP ) to be associated with fracture risk in women . However , it is still unclear whether hs-CRP is also associated with fracture risk in men . We therefore measured serum levels of hs-CRP in 2910 men , mean age 75 years , included in the prospect i ve population -based MrOS Sweden cohort . Study participants were divided into tertile groups based on hs-CRP level . Fractures occurring after the baseline visit were vali date d ( average follow-up 5.4 years ) . The incidence for having at least one fracture after baseline was 23.9 per 1000 person-years . In Cox proportional hazard regression analyses adjusted for age , hs-CRP was related to fracture risk . The hazard ratio ( HR ) of fracture for the highest tertile of hs-CRP , compared with the lowest and the medium tertiles combined , was 1.48 ( 95 % CI , 1.20–1.82 ) . Multivariate adjustment for other risk factors for fractures had no major effect on the associations between hs-CRP and fracture . Results were essentially unchanged after exclusion of subjects with hs-CRP levels greater than 7.5 mg/L , as well as after exclusion of subjects with a first fracture within 3 years of follow-up , supporting that the associations between hs-CRP and fracture risk were not merely a reflection of a poor health status at the time of serum sampling . Femoral neck bone mineral density ( BMD ) was not associated with hs-CRP , and the predictive role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD was added to the model ( HR , 1.37 ; 95 % CI , 1.09–1.72 ) . Exploratory subanalyses of fracture type demonstrated that hs-CRP was clearly associated with clinical vertebral fractures ( HR , 1.61 ; 95 % CI , 1.12–2.29 ) . We demonstrate , using a large prospect i ve population -based study , that elderly men with high hs-CRP have increased risk of fractures , and that these fractures are mainly vertebral . The association between hs-CRP and fractures was independent of BMD The prevalence of osteopenia among patients with inflammatory bowel disease ranges from 40 % to 50 % , and frank osteoporosis is seen in 2 % to 30 % of patients ( 1 - 5 ) . These estimates are based on measurement of bone mineral density , in which osteoporosis is defined as a bone mass T-score less than 2.5 ( 6 ) . Much has been written about the prevalence and causes of osteopenia , and a few reports have been published on the treatment of osteopenia in inflammatory bowel disease ( 7 - 9 ) . However , the clinical importance of osteopenia among persons with inflammatory bowel disease is unclear because no data have been published on the actual risk for fracture in persons with inflammatory bowel disease . The most common fractures associated with osteoporosis are those of the hip , spine , and distal radius ( 10 ) . Rib fractures are also of interest since they are common among persons with low bone mass ( 11 ) . We sought to determine whether persons with inflammatory bowel disease had an increased risk for these fractures compared with persons without inflammatory bowel disease . Methods The incidence of fracture in a cohort of persons with inflammatory bowel disease was compared with that in a cohort of persons without inflammatory bowel disease , matched 1 to 10 to the inflammatory bowel disease cohort by age , sex , and geographic location of residence . The inflammatory bowel disease cohort ( n = 6027 ) consisted of persons in the population -based University of Manitoba IBD Data base , which has been described elsewhere ( 12 ) . In brief , the data base was developed by using Manitoba Health administrative data bases . Manitoba Health ( Government of Manitoba ) provides comprehensive health care coverage for residents of Manitoba , Canada ( population , 1.14 million ) . Since Manitoba residents are not obliged to pay premiums for health care coverage , nonparticipation in the plan is rare . Manitoba Health maintains computerized data bases of physician services and hospitalizations for all persons registered with the system . Each physician service record includes information on the identity of the patient , the date of service , services provided , and diagnosis , which is subsequently coded as a three-digit International Classification of Diseases , Ninth Edition , Clinical Modification ( ICD-9-CM ) code . After each hospitalization , a detailed abstract is created that includes up to 16 diagnoses coded as five-digit ICD-9-CM codes . By extracting physician service records and hospitalizations for all Manitoba residents from 1984 to 1997 , we created a population -based data base of all persons who had received a diagnosis of Crohn disease ( ICD-9-CM code 555.xx ) or ulcerative colitis ( ulcerative colitis ) ( ICD-9-CM code 556.xx ) . The cohort of persons without inflammatory bowel disease was created by r and omly selecting 10 persons without inflammatory bowel disease from the Manitoba Health population registry . These 60 270 controls were matched to persons with inflammatory bowel disease by year of birth , sex , and postal area of residence at the date of diagnosis of the index case of inflammatory bowel disease . The incidence of hospitalization for hip fracture was calculated by using the Manitoba Health administrative data base for hospital discharge abstract s ( using ICD-9-CM code 820.xx ) . Outpatient health system contacts and hospitalization contacts  for  spine fractures  ( ICD-9-CM code 806.xx ) ,  rib fractures ( ICD-9-CM 807.0x to 807.1x ) and wrist/forearm fractures  ( ICD-9-CM 813.xx ) were analyzed in a similar fashion . Incidence rates were calculated on the basis of person-years of follow-up for 1984 to 1997 . Incidence rate ratios ( IRRs ) and 95 % CIs were calculated by comparing the incidence of fracture in persons with inflammatory bowel disease with that in controls , using Poisson regression . To determine whether enhanced physician contact and an increased frequency of  radiography  in persons with inflammatory bowel disease influenced the estimated incidence of rib , forearm , and spine fractures , we performed supplementary analyses in which we excluded all persons who had undergone radiography of the chest , ribs , abdomen , or spine in the 2 years before the date of fracture . The construction of the University of Manitoba IBD Data base and its use in clinical studies were approved by the University of Manitoba Research Ethics Board and by the Access and Confidentiality Committee of Manitoba Health and was funded by the National Health and Research Development Program of Canada . Comparison of persons with inflammatory bowel disease with matched controls was performed without external funding . Results Person-years of follow-up were 21 340 for Crohn disease and 19 665 for ulcerative colitis . The mean age at the start of follow-up was 36.3 16.7 years for persons with Crohn disease and 42.0 18.0 years for persons with ulcerative colitis . Forty-one percent of persons with Crohn disease and 50 % of those with ulcerative colitis were male . Overall , 405 incident fractures occurred among persons with inflammatory bowel disease , for an incidence of 98.8 per 10 000 persons ( Table 1 ) . The incidence of  fractures  among persons with inflammatory bowel disease increased with advancing age for all fracture sites ( Table 1 ) . This was particularly true for hip fractures , which occurred mostly among persons older than 60 years of age and were rare among persons younger than 40 years of age . The overall crude incidence rate of fractures was higher in persons with ulcerative colitis than those with Crohn disease . This finding reflects the older age distribution of persons with ulcerative colitis , since fracture rates were similar in each age stratum ( Table 1 ) . Table 1 . Crude Incidence of Fracture  among Persons with Inflammatory Bowel Disease in Manitoba , Canada , 19841997 Compared with controls , persons with inflammatory bowel disease had a significantly elevated incidence of fracture at the hip ( IRR , 1.59 [ 95 % CI , 1.27 to 2.00 ] ; P<0.001 ) , spine ( IRR , 1.74 [ CI , 1.34 to 2.24 ] ; P<0.001 ) , wrist/forearm ( IRR , 1.33 [ CI , 1.11 to 1.58 ] ; P=0.001 ) , and rib ( IRR , 1.25 [ CI , 1.02 to 1.52 ] ; P=0.03 ) ( Table 2 ) . For these fractures combined , persons with inflammatory bowel disease had an increased incidence of approximately 40 % ( IRR , 1.41 [ CI , 1.27 to 1.56 ] 
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Similarly , another study reported that per doubling of CRP was positive only when CRP > 3 mg/L. Conclusion In summary , the present analysis showed that the relationship between CRP concentrations and  subsequent fracture risk is still inconsistent .