***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study was performed to investigate the effects of the co-administration of proton pump inhibitor ( PPI ) on the efficacy of bisphosphonate ( BP ) treatment for osteoporosis . A total of 180 women with low bone mineral density were r and omly divided into four groups , one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered ( BP + PPI and BP groups , respectively ) . The biomarkers were measured at the baseline and every 3 months , inlcuding : N-terminal telopeptide of type I collagen corrected for creatinine , bone-specific alkaline phosphatase ( BAP ) , parathyroid hormone , bone mineral density ( BMD ) of the lumbar spine and physical parameters evaluated according to the SF-36v2 ™ Health Survey . Statistical comparisons of these parameters were performed after 9 months . Data were available for a total of 137 patients ( 62 in the BP group and 75 in the BP + PPI group ) . The Δ % value of increase in BMD and improvement of physical functioning in the BP + PPI group were significantly larger , and its decrease in BAP in the BP + PPI group was significantly smaller than that in the BP group . It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone We studied the effect of proton pump inhibitors , histamine H2 receptor antagonists , and other types of antacid drugs on  fracture risk . All cases were subjects with any fracture sustained during the year 2000 ( n = 124,655 ) . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of proton pump inhibitors , histamine H2 antagonists , and other antacid drugs . Adjustments were made for several confounders , including diagnosis of an ulcer , nonsteroidal anti-inflammatory drug use , use of histamine H1 antagonists , stomach resection , previous fracture , and use of corticosteroids . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose ) . Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [ odds ratio ( OR ) = 1.18 , 95 % confidence interval ( CI ) 1.12–1.43 for overall fracture risk ; OR = 1.45 , 95 % CI 1.28–1.65 for hip fractures ; and OR = 1.60 , 95 % CI 1.25–2.04 for spine fractures ) . Histamine H2 antagonists were associated with a decreased fracture risk if they had been used within the last year ( OR = 0.88 , 95 % CI 0.82–0.95 for any fracture , OR = 0.69 , 95 % CI 0.57–0.84 for hip fractures ) . Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures . Proton pump inhibitors appeared to be associated with a limited increase in fracture risk , in contrast to histamine H2 antagonists , which seemed to be associated with a small decrease in fracture risk . In all cases , the changes in risk estimates were small and the clinical significance was limited BACKGROUND No studies have estimated disability-adjusted life-years ( DALYs ) lost due to hip fractures using real-life follow-up cohort data . We aim ed to quantify the burden of disease due to incident hip fracture using DALYs in prospect i ve cohorts in the CHANCES consortium , and to calculate population attributable fractions based on DALYs for specific risk factors . METHODS We used  data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs . We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates . We calculated population attributable fractions for  smoking  ,  body-mass index ( BMI ) , physical activity , alcohol intake , type 2 diabetes and parity , use of hormone replacement therapy , and oral contraceptives in women . We calculated summary risk estimates across cohorts with pooled analysis and r and om-effects meta- analysis methods . FINDINGS 223 880 men and women were followed up for a mean of 13 years ( SD 6 ) . 7724 ( 3·5 % ) participants developed an incident hip fracture , of whom 413 ( 5·3 % ) died as a result . 5964 DALYs ( 27 per 1000 individuals ) were lost due to hip fractures , 1230 ( 20·6 % ) of which were in the group aged 75 - 79 years . 4150 ( 69·6 % ) DALYs were attributed to disability . Current smoking was the risk factor responsible for the greatest hip fracture burden ( 7·5 % , 95 % CI 5·2 - 9·7 ) followed by physical inactivity ( 5·5 % , 2·1 - 8·5 ) , history of diabetes ( 2·8 % , 2·1 - 4·0 ) , and low to average BMI ( 2·0 % , 1·4 - 2·7 ) , whereas low alcohol consumption ( 0·01 - 2·5 g per day ) and high BMI had a protective effect . INTERPRETATION Hip fracture can lead to a substantial loss of healthy life-years in elderly people . National public health policies should be strengthened to reduce hip fracture incidence and mortality . Primary prevention measures should be strengthened to prevent falls , and reduce smoking and a sedentary lifestyle . FUNDING European Community 's Seventh Framework Programme Proton pump inhibitors are taken by millions of patients for prevention and treatment of gastroesophageal diseases . Case-control studies have suggested that use of omeprazole is associated with an increased risk of hip fractures . The aim of this prospect i ve study was to assess the risk of vertebral fractures in postmenopausal women using omeprazole .  We studied 1,211 postmenopausal women enrolled in the Osteoporosis and Ultrasound Study from the general population . Information on omeprazole and other risk factors for fractures including prevalent fractures and bone mineral density was obtained at baseline . Vertebral fractures were assessed on X-rays obtained at baseline and at the end of the 6-year follow-up and analyzed central ly . At baseline , 5 % of this population was using omeprazole .  Age-adjusted rates for vertebral fractures were 1.89 and 0.60 for 100 person-years for omeprazole users and nonusers , respectively ( P = 0.009 ) . In the multivariate analysis , omeprazole use was a significant and independent predictor of vertebral fractures ( RR = 3.50 , 95 % CI 1.14–8.44 ) . The other predictors were age higher than 65 years ( RR = 2.34 , 95 % CI 1.02–5.34 ) , prevalent vertebral fractures ( RR = 3.62 , 95 % CI 1.63–8.08 ) , and lumbar spine T score ≤ −2.5 ( RR = 2.38 , 95 % CI 1.03–5.49 ) . Omeprazole use is associated with an increased risk of vertebral fractures in postmenopausal women . Further studies are required to determine the mechanism of the association between the underlying gastric disease , omeprazole  use , and  risk of osteoporotic fractures Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To examine the association between chronic use of proton pump inhibitors ( PPIs ) and risk of hip fracture .  Design Prospect i ve cohort study . Setting Nurses ’ Health Study , which originally recruited from the 11 most populous states in the US . Participants 79 899 postmenopausal women enrolled in the Nurses ’ Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008 . Main outcome measure Incident hip fracture Results During 565 786 person years of follow-up , we documented 893 incident hip fractures . The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years , compared with 1.51 events per 1000 person years among non-users . Compared with non-users , the risk of hip fracture among women who regularly used PPIs for at least two years was 35 % higher ( age adjusted hazard ratio 1.35 ( 95 % confidence interval 1.13 to 1.62 ) ) , with longer use associated with increasing risk ( Ptrend<0.01 ) . Adjustment for risk factors , including body mass index , physical activity , and intake of calcium did not material ly alter this association ( hazard ratio 1.36 ( 1.13 to 1.63 ) ) . These associations were also not changed after accounting for reasons for PPI use . The relation between PPI use and fracture differed by smoking history ( Pinteraction=0.03 ) . Among current and former smokers , PPI use was associated with greater than 50 % increase in risk of fracture , with a multivariate hazard ratio for fracture of 1.51 ( 1.20 to 1.91 ) . In contrast , among women who never smoked there was no association ( multivariate hazard ratio 1.06 ( 0.77 to 1.46 ) ) . In a meta- analysis of these results with 10 prior studies , the pooled odds ratio of hip fracture associated with PPI use was 1.30 ( 1.25 to 1.36 ) . Conclusion Chronic use of PPIs is associated with increased risk of hip fracture  , particularly among women with a history of smoking Summary A large Canadian cohort was studied over 10 years to see if proton pump inhibitor ( PPI ) use increased the risk of sustaining a fragility fracture . We found an increased risk of fracture in individuals who used PPIs .  The risk remained after controlling for other known fracture risk factors . Introduction Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture . We prospect ively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors . Methods We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study . The cohort was formed in 1995–1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use . Cox regression analyses were used to assess the association between  PPI  use and incident fracture risk . Results PPI use , coded as a time-dependent variable , was associated with a shorter time to first nontraumatic fracture , hazard ratio ( HR ) = 1.75 ( 95 % confidence interval ( CI ) 1.41–2.17 , p < 0.001 ) . After controlling for multiple risk factors , including femoral neck bone density , the association remained significant , HR = 1.40 ( 95 % CI 1.11–1.77 , p = 0.004 ) . Similar results were obtained after controlling for bisphosphonate use , using PPI “ ever ” use , or when the outcome was restricted to hip fracture . Conclusions In this large prospect i ve population -based cohort study , we found an association between PPI use and increased risk of fragility fracture . Although the increased risk found was modest , this finding is important , given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures BACKGROUND Proton pump inhibitor ( PPI ) medications have been inconsistently shown to be associated with  osteoporotic fractures .  We examined the association of PPI use with bone outcomes ( fracture , bone mineral density [ BMD ] ) . METHODS This prospect i ve analysis included 161 806 postmenopausal women 50 to 79 years old , without history of hip fracture , enrolled in the Women 's Health Initiative ( WHI ) Observational Study and Clinical Trials with a mean ( SD ) follow-up of 7.8 ( 1.6 ) years . Analyses were conducted for 130 487 women with complete information .  Medication information was taken directly from drug containers during in-person interviews ( baseline , year 3 ) . The main outcome measures were self-reported fractures ( hip [ adjudicated ] , clinical spine , forearm or wrist , and total fractures ) and for a sub sample ( 3 densitometry sites ) , 3-year change in BMD . RESULTS During 1 005 126 person-years of follow-up , 1500 hip fractures , 4881 forearm or wrist fractures , 2315 clinical spine fractures , and 21 247 total fractures occurred . The 
    Output:
    
This meta- analysis suggests that PPI user have a 26 % increased risk of hip fracture as compared to non-PPI user .