title: Does an educational leaflet improve self-reported adherence to therapy in osteoporosis? The OPTIMA study Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study* Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. Studies of the oral bioavailability of alendronate The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE.
abstract: Introduction Adherence to treatment in osteoporosis remains poor . The aim of this study was to evaluate the effects of an educational leaflet on adherence to medication and to assess the association between adherence and health-related quality of life ( HRQOL ) . Methods A naturalistic , observational , multi-center , prospect i ve study of 12 months ’ follow-up was performed . Consecutive post-menopausal women aged 50 years to 86 years starting treatment with raloxifene according to daily practice were enrolled from 126 primary care offices in Spain . The women were assigned to two study groups . Group A received an educational leaflet with general information about osteoporosis ; group B followed current practice . To assess adherence to medication and HRQOL , the Morisky test and the EuroQoL question naire were administered . A total of 745 post-menopausal women ( group A , n=366 ; group B n=379 ) , with a mean age of 62 years , were included . Results Most patients in both study groups showed high adherence to raloxifene at the 3-month visit : 56.3 % vs 62.7 % for groups A and B , respectively ; this proportion at the 12-month visit was 47.4 % ( P=0.15 ) and 52.5 % ( P=0.02 ) , respectively . At baseline , “ pain/discomfort ” was the dimension showing the highest percentage of women reporting problems : 86.4 % vs 83.2 % in groups A and B , respectively ( P=0.22 ) . HRQOL improved in both groups throughout the study , with an overall mean increment in the EuroQoL visual analog scale ( EQ VAS ) of 9.2 at 12 months ( P<0.01 ) . Correlations between adherence and HRQOL were weak . After receiving an educational leaflet , young post-menopausal women suffering osteoporosis did not show improvement in adherence to therapy . HRQOL improved at 12-month follow-up under treatment . Conclusion No consistent correlation between adherence and HRQOL was found Osteoporosis is a common and debilitating condition associated with significant morbidity and mortality . The efficacy and safety of oral bisphosphonates for the treatment of osteoporosis are well established . However , patient adherence and persistence on treatment are suboptimal . This r and omised open-label multi-centre study of 6-months ’ duration compared persistence on treatment in postmenopausal women with osteoporosis receiving either once-monthly ib and ronate plus a patient support programme ( PSP ) , or once-weekly alendronate .  To avoid falsely elevated persistence rates often associated with clinical trials , the study was design ed to reflect everyday clinical practice in the UK and follow-up visits were limited to be consistent with the primary care setting . Analysis of the primary endpoint showed that persistence was significantly higher in the ib and ronate/PSP group compared with the alendronate group ( p < 0.0001 ) . The estimated proportion of patients persisting with treatment at 6 months was 56.6 % ( 306/541 ) and 38.6 % ( 198/513 ) in the ib and ronate/PSP and alendronate groups , respectively . Therefore , compared with alendronate , there was a 47 % relative improvement in the proportion of patients persisting with treatment in the ib and ronate/PSP group . Secondary endpoint measurements of adherence ( e.g. proportion of patients remaining on treatment at study end ; proportion of patients discontinuing from the study ) were also significantly different in favour of ib and ronate plus patient support . In summary , the PERSIST study demonstrated that persistence on treatment was increased in patients receiving once-monthly ib and ronate plus patient support compared with once-weekly alendronate .  Increased persistence on bisphosphonate treatment is expected to improve patient outcomes and decrease the social and economic burden of osteoporosis CONTEXT Persistence with osteoporosis treatment is poor but is important for maximum benefit . OBJECTIVE The objective of the study was to assess the impact of physician reinforcement using bone turnover markers ( BTMs ) on persistence with risedronate treatment . DESIGN AND SETTING This was a 1-yr multinational prospect i ve , open-label , blinded study in 171 osteoporosis centers in 21 countries . PATIENTS A total of 2382 postmenopausal women ( 65 - 80 yr old ) with spine/hip T-score -2.5 or less or T-score -1.0 or less with a low-trauma fracture . INTERVENTION Intervention included calcium 500 mg/d , vitamin D 400 IU/d , and risedronate 5 mg/d for 1 yr . Centers were r and omized to reinforcement ( RE+ ) or no reinforcement ( RE- ) . At 13 and 25 wk , reinforcement based on urinary N-telopeptide of type I collagen change from baseline was provided to the RE+ patients using the following response categories : good ( > 30 % decrease ) , stable ( -30 % to + 30 % change ) , or poor ( > 30 % increase ) . MAIN OUTCOME MEASURES Persistence assessed with electronic drug monitors was measured . RESULTS In the overall efficacy population ( n=2302 ) , persistence was unexpectedly high and was similar for both groups ( RE- , 77 % ; RE+ , 80 % ; P=0.160 ) . A significant relationship between the type of message and persistence was observed ( P=0.017 ) . Compared with RE- , intervention based on a good BTM response was associated with a significant improvement in persistence [ hazard ratio ( HR ) 0.71 ; 95 % confidence interval ( CI ) 0.53 - 0.95 ] . Persistence was unchanged ( HR 1.02 ; 95 % CI 0.74 - 1.40 ) or lower ( HR 2.22 ; 95 % CI 1.27 - 3.89 ) when reinforcement was based on a stable or poor BTM response , respectively . Reinforcement was associated with a lower incidence of new radiologically determined vertebral fractures ( odds ratio 0.4 ; 95 % CI , 0.2 - 1.0 ) . CONCLUSIONS Reinforcement using BTMs influences persistence with treatment in postmenopausal women with osteoporosis , depending on the BTM response observed Clinical studies were performed to examine the oral bioavailability of alendronate ( 4‐amino‐1‐hydroxybutylidene‐1,1‐bisphosphonate monosodium ) . All studies , with the exception of one performed in men , involved postmenopausal women . Short‐term ( 24 to 36 hours ) urinary recovery of alendronate after an intravenous dose of 125 to 250 μg averaged about 40 % in both men and women . In  women , oral bioavailability of  alendronate  was independent of dose ( 5 to 80 mg ) and averaged ( 90 % confidence interval ) 0.76 % ( 0.58 , 0.98 ) when taken with water in the fasting state , followed by a meal 2 hours later . Bioavailability was similar in men [ 0.59 % , ( 0.43 , 0.81 ) ] . Taking alendronate either 60 or 30 minutes before a st and ardized breakfast reduced bioavailability by 40 % relative to the 2‐hour wait . Taking alendronate either concurrently with or 2 hours after breakfast drastically ( > 85 % ) impaired availability . Black coffee or orange juice alone , when taken with the drug , also reduced bioavailability ( approximately 60 % ) . Increasing gastric pH , by infusion of ranitidine , was associated with a doubling of alendronate bioavailability . A practical dosing recommendation , derived from these findings and reflective of the long‐term nature of therapy for a disease such as osteoporosis , is that patients take the drug with water after an overnight fast and at least 30 minutes before any other food or beverage Long-term adherence and persistence with any therapy are very poor ( approximately 50 % ) . Adherence to therapy is defined as the percentage of prescribed medication taken , and persistence is defined as continuing to take prescribed medication . We examined whether monitoring by nursing staff could enhance adherence and persistence with antiresorptive therapy and whether presenting information on response to therapy provided additional benefit . In addition we evaluated the impact of monitoring on treatment efficacy . Seventy-five postmenopausal women with osteopenia were r and omized to 1 ) no monitoring , 2 ) nurse-monitoring , or 3 ) marker-monitoring . All subjects were prescribed raloxifene .  At 12 , 24 , and 36 wk , the nursing staff review ed subjects in the monitored ( nurse-monitoring or marker-monitoring ) groups using a predefined protocol . The marker-monitored group were also presented a graph of response to therapy using percentage change in urinary N-telopeptide of type I collagen ( uNTX ) , a bone resorption marker , at each visit . Biological response to therapy at 1 yr was determined using the percent change in bone mineral density ( BMD ) and uNTX . Treatment adherence and persistence were assessed using electronic monitoring devices . Survival analysis showed that the monitored group increased cumulative adherence to therapy by 57 % compared with no monitoring ( P = 0.04 ) . There was a trend for the monitored group to persist with therapy for 25 % longer compared with no monitoring ( P = 0.07 ) . Marker measurements did not improve adherence or persistence to therapy compared with nurse-monitoring alone . Adherence at 1 yr was correlated with percent change in hip ( BMD ) ( r = 0.28 ; P = 0.01 ) and percent change in uNTX ( r = -0.36 ; P = 0.002 ) . In conclusion , monitoring of patients increased adherence to therapy by 57 % at 1 yr . Increased adherence to therapy increased the effectiveness of raloxifene therapy determined using surrogate end points OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE
target: trials to date suggest potential for improving persistence with medication taking thus improving treatment outcomes and reducing fracture risk .
  More precise measurement of medication taking and promoting fidelity to a precisely defined intervention protocol may lead to better assessment of impact on clinical ly important outcomes
background: BACKGROUND despite availability of effective treatments for osteoporosis , impact on fracture rates may be suboptimal because of failure to adhere to recommended anti-resorptive therapy .
  OBJECTIVE to identify r and omized controlled trials ( RCTs ) evaluating interventions intended to improve persistence with anti-resorptive therapy for treating women with osteoporosis or osteopenia .