A systematic review of the effectiveness of interventions to improve post-fracture investigation and management of patients at risk of osteoporosis Appropriate use of anabolic treatment for severe osteoporosis. Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study. Treatment of Postmenopausal Osteoporosis with Slow-Release Sodium Fluoride: Final Report of a Randomized Controlled Trial Interventions to improve osteoporosis treatment following hip fracture. A prospective, randomized trial. Population screening for osteoporosis risk: a randomised control trial of medication use and fracture risk Use of a decision aid to improve treatment decisions in osteoporosis: the osteoporosis choice randomized trial. Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group. Persistence, reproducibility, and cost-effectiveness of an intervention to improve the quality of osteoporosis care after a fracture of the wrist: results of a controlled trial How the knowledge of fracture risk might influence adherence to oral therapy of osteoporosis in Italy: the ADEOST study Randomized controlled trial of a primary care–based screening program to identify older women with prevalent osteoporotic vertebral fractures: Cohort for skeletal health in Bristol and Avon (COSHIBA) Antiresorption therapy and reduction in fracture susceptibility in the osteoporotic elderly patient: open study. Protocol for the Osteoporosis Choice trial. A pilot randomized trial of a decision aid in primary care practice Nurse case-manager vs multifaceted intervention to improve quality of osteoporosis care after wrist fracture: randomized controlled pilot study Relative Effectiveness of Osteoporosis Drugs for Preventing Nonvertebral Fracture Community based intervention to optimize osteoporosis management: randomized controlled trial Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial
Background There is a large quality of care gap for patients with osteoporosis . As a fragility fracture is a strong indicator of underlying osteoporosis , it offers an ideal opportunity to initiate investigation and treatment . However , studies of post-fracture population s document screening and treatment rates below 20 % in most setting s. This is despite the fact that bone mineral density ( BMD ) scans are effective at identifying patients at high risk of fracture , and effective drug treatments are widely available . Effective interventions are required to remedy this incongruity in current practice . Methods This study review ed r and omised controlled trials ( RCT ) involving fully qualified healthcare professionals caring for patients with a fragility fracture in all healthcare setting s. Any intervention design ed to modify the behaviour of healthcare professionals or implement a service delivery change was considered . The main outcomes were  BMD scanning and osteoporosis treatment with anti-resorptive therapy .  The electronic data bases Medline and Embase were search ed from 1994 to June 2010 to identify relevant articles in English .  Post-intervention risk differences ( RDs ) were calculated for the main outcomes and any additional study primary outcomes ; the trials were meta-analysed . Results A total of 2814 potentially relevant articles were sifted ; 18 were assessed in full text . Nine RCTs evaluating ten interventions met the inclusion criteria for the review . All were from North America . Four studies focused on patients with a hip fracture , three on fractures of the wrist/distal forearm , and two included several fracture sites consistent with a fragility fracture . All studies reported positive effects of the intervention for the main study outcomes of BMD scanning and osteoporosis treatment . For BMD scanning the overall risk ratio ( 95 % CI ) was 2.8 ( 2.16 to 3.64 ) ; the RD was 36 % ( 21 % to 50 % ) . For treatment with anti-resorptive therapy the overall risk ratio ( 95 % CI ) was 2.48 ( 1.92 to 3.2 ) ; the RD was 20 % ( 10 % to 30 % ) . Conclusions All interventions produced positive effects on BMD scanning and osteoporosis treatment rates post-fracture . Despite sizeable increases , investigation and treatment rates remain sub-optimal . Long-term compliance with osteoporosis medications needs to be addressed , as the majority of studies reported treatment rates at six-month follow up only . Studies would be more informative if treatment criteria were defined a priori to facilitate underst and ing of whether patients were being treated appropriately and integrated economic analyses would be helpful for informing policy implementation decisions Osteoporotic fractures remain a major public health problem for their correlated morbidity and mortality . The primary aim of therapy must be the prevention of the first fragility fracture and avoiding subsequent fractures in patients who already have an existing fracture . There are evidence s from r and omized controlled trials ( RCTs ) about the efficacy of antiresorptives , such as bisphosphonates in reducing the risk of fracture , but none of these agents completely abolish the fracture risk . The reduction of RRR by different therapies in RCTs is relatively constant but it is important to note that the proportion of inadequate-responders ( i.e. : patients fracturing despite adequate pharmacological treatment ) is increasing with the severity of the disease : the higher the risk of fracture the higher the proportion of inadequate-responders . Thus , the proportion of non responders across different trials is directly related to the fracture incidence observed in the control group of RCTs which is the most proximate indicator of osteoporosis severity . Teriparatide ( TPTD ) demonstrate a real increases of both trabecular and cortical bone volume , which are associated with a true reduction of fracture risk , as many RCTs confirm . The beneficial effect of introducing a treatment with antiresorptives after the treatment course with TPTD has been clearly demonstrated with the prevention of the reabsorption of the new bone tissue built during TPTD therapy and rapidly lowers cortical porosity , which leads to further increases in BMD . For these results , the introduction of an anti-resorptive after the treatment course with TPTD is strongly recommended and taken into account . In Italy TPTD is fully reimbursed in patients incurring in a new vertebral or hip fracture while on chronic treatment with antiresorptive or in naive patients with 3 or more vertebral or hip fractures . In conclusion , since patients with severe osteoporosis are at very high risk of new fractures with worsening of quality of life and life expectancy , antiresorptives represent a sub-optimal treatment in these patients , werehas , since TPTD demonstrated real and substantial improvements in bone mass and reduction of fracture risk independently of initial risk , TPTD represents the only therapeutic option able to reverse at least in part this disabling disease UNLABELLED None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures . In clinical practice , the outcome may be even poorer . In 880 patients prescribed with antiresorptives ( alendronate , risedronate , and raloxifene ) for > 1 year , a  fragility fracture  was recorded in 8.9%/year of them . This incidence is considerably higher than that observed in r and omized clinical trials , and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D. INTRODUCTION Osteoporotic fracture is one of the most important public health concerns among the elderly . Currently available therapies have been shown to significantly decrease the risk of fracture , although none of them completely abolishes this risk . In clinical practice , poor treatment response may also result from a number of other factors . MATERIAL S AND METHODS The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis ( ICARO ) is a multicenter , observational study carried out in Italy . It aim ed to analyze , in postmenopausal women with established osteoporosis , the risk factors for an " inadequate clinical response " to drug therapy , defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed , for at least 1 year , alendronate , risedronate , or raloxifene , with a compliance > 50 % . RESULTS In 880 patients treated with antiresorptive agents  for a median of 2.0 years ( 95 % CI : 1.0 - 4.5 ) years , the " inadequate clinical responder ( ICR ) " subjects over the observation period were 220 ( 25 % ) , with an annual incidence of 8.9 % . ICRs , compared with " adequate clinical responders ( ACRs ) , " had more pretreatment fractures and were treated longer ( 2.8 versus 1.8 years ; p < 0.001 ) . After multiple adjustment for these confounding factors , significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements . CONCLUSIONS The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in r and omized clinical trials . Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response It seems logical to use fluoride in osteoporosis , because fluoride can stimulate osteoblastic proliferation and new bone formation [ 1 , 2 ] . However , clinical trials with fluoride have yielded mixed results because excessive exposure to fluoride may cause abnormal bone formation , microfractures , and gastric bleeding [ 3 , 4 ] . Thus , treatment with a high dosage of plain sodium fluoride did not decrease the spinal fracture rate despite markedly increasing vertebral bone density , and it increased the rate of appendicular fractures and microfractures [ 4 ] . To overcome the complications associated with sodium fluoride , we have advocated the cyclical , intermittent use of a lower dose of less bioavailable , slow-release sodium fluoride and continuous supplementation with calcium citrate [ 5 , 6 ] . This treatment has been shown to maintain serum fluoride concentrations within the narrow therapeutic window [ 7 , 8 ] , thus avoiding toxic peaks in serum [ 9 ] , and to stimulate the formation of normally mineralized bone [ 5 , 10 ] with an improved intrinsic quality of cancellous bone [ 11 - 13 ] . We previously reported the results of an interim analysis [ 6 ] of a placebo-controlled r and omized trial ( median duration of treatment for fracture analysis , 2 years ) . Here , we present the final report of that trial ( median duration of treatment for fracture analysis , 3 years ) . Methods Clinical Data Demographic and baseline presentations were described in the interim report [ 6 ] . We recruited 110 women with postmenopausal osteoporosis into the trial . All had radiologic evidence of osteopenia and osteoporosis ; one or more vertebral fractures believed to be nontraumatic ; and no secondary cause of bone loss . They were r and omly assigned to one of two groups and stratified according to estrogen treatment . All study personnel were unaware of group assignment while data were being gathered . Ninety-nine patients completed at least 1 study cycle ( 1 year of actual treatment ) . The demographic or baseline presentations of these 99 patients did not differ according to treatment group [ 6 ] ( Table 1 ) . The two groups were similar in age , time since menopause , dietary calcium intake , height , weight , and number of spinal fractures . Both groups had moderate to severe osteoporosis : The average L2-L4 bone density was approximately 30 % less than of a normal 30-year-old woman , and each group had a median of two spinal fractures at baseline . Table 1 . Baseline Characteristics * Treatment Patients in the fluoride group received slow-release sodium fluoride ( Slow Fluoride , Mission Pharmacal Co. , San Antonio , Texas ) , 25 mg twice daily , orally before breakfast and at bedtime in repeated 14-month cycles ( 12 months receiving treatment followed by 2 months not receiving treatment ) . They also received calcium citrate ( Citracal , Mission Pharmacal ) , 400 mg calcium twice daily , before breakfast and at bedtime continuously throughout the study . Those in the placebo group received placebo ( identical in appearance to Slow Fluoride but containing excipient only [ provided by Mission Pharmacal ] ) on the same time schedule . The Mission Pharmacal Company had no role in the design of the study or in data retrieval , analysis , or interpretation . Thirteen of 48 patients in the fluoride group and 16 of 51 patients in the placebo group received concurrent treatment with estrogen .  Nine of the 29 patients treated with estrogen were recruited at the primary site at Dallas ; the other 20 were enrolled and evaluated at the Scott and White Clinic , Temple , Texas .  Fracture Quantitation Before treatment and at 12 months of each cycle , a lateral spine roentgenogram was obtained for the assessment of spinal fractures . In the interim analysis [ 6 ] , prevalent fractures ( fractures present at baseline ) were identified with the aid of radiology reports . For this final report , prevalent fractures were also analyzed using a computer program that calculated the vertebral dimensions of clearly unaffected vertebrae from l and marks ( anterior and posterior corners and midpoints ) . By comparing these dimensions with published normal values [ 14 ] , we obtained a correction factor . Using this correction factor , we estimated idealized vertebral dimensions before a fracture had occurred for the remaining vertebrae in the given baseline radiograph . A reduction in any height of more than 20 % ( from idealized to actual ) accompanied by a decrease of at least 10 % in vertebral area represented a prevalent fracture . Incident spinal fractures ( fractures occurring during the trial ) were identified as described previously [ 6 ] , using a computer-derived method . A reduction in any vertebral height of more than 20 % accompanied by a decrease in vertebral area of more than 10 % from one year to the next constituted a fracture [ 15 ] . A new incident fracture was a fracture that occurred during treatment in a previously unaffected vertebrae . A recurrent fracture was one that developed on a previously fractured vertebra . Bone Mass Measurements The use of different densitometers prompted us to calculate and use percentage changes per year rather than absolute values . The method for calculating changes in L2-L4 bone mineral content and bone density of the femoral neck and the radial shaft was described previously [ 6 ] . Safety Variables Serum fluoride concentrations were measured before the morning dose of the test drug at 0 , 3 , 6 , 9 , and 12 months of each cycle , and they were analyzed using an ion-specific electrode . At the same visits , a history was taken for gastrointestinal and musculoskeletal side effects . A microfracture was defined clinical ly as moderate to severe lower-extremity pain that persisted for more than 6 weeks despite a reduction in treatment dose and objective ly as changes on bone scan or radiograph . The relation of each side effect to treatment was assessed . A symptom was considered to be related to treatment if it was moderate to severe in intensity , had no other cause , had newly appeared and persisted during the treatment phase , or had disappeared during the withdrawal period or with dose reduction . It was considered to be unrelated if it was present at baseline or during the late withdrawal phase , or if it had newly appeared but was not persistent . The severity and frequency of side effects were also quantitated as adverse symptom scores . We identified 10 gastrointestinal items ( symptoms such as nausea , vomiting , and diarrhea ) , 4 rheumatic items ( pain in the foot , knee , hip , and other joints ) , and 3 skeletal items ( pain in the lower , mid- , or upper back ) . Each item was given a numerical value of 1 to 3 for frequency ( infrequent , frequent , or very frequent ) and a numerical value of 1 to 3 for severity ( mild , moderate , or severe ) . Side-effect score was the product of the value for frequency and the value for severity for each item . Thus , a constant , severe back pain yielded a score of 9 ( 3 3 ) . A gastrointestinal score was derived for each patient by adding the scores of the 10 gastrointestinal items for all relevant visits and dividing the sum by the number of visits . A similar computation was done to derive rheumatic and skeletal scores for each patient . Statistical Analysis The data for incident spinal fractures were compared between the two groups-using three methods . Individual Vertebral Fracture Rate For each patient , the individual vertebral fracture rate was obtained by dividing the total number of new fractures by the duration of treatment . Because the data were skewed , this rate was compared between the two groups using the Wilcoxon rank-sum test . Fracture-Free Rate This rate was the percentage of patients without new fractures , unadjusted for covariates . The two groups were compared using the log-rank test to account for differential follow-up . Survival The Cox proportional-hazards regression model [ 16 ] was constructed to estimate the relative risk for a new spinal fracture while adjusting for covariates ( treatment group , age , prevalent spinal fractures , years since menopause , height , weight , estrogen treatment , and stratum of baseline L2-L4 bone density ) . Time ( in years ) to the first fracture was considered to be the survival time . Analyses of fracture rates and logistic regression were also done [ 6 ] ; the data are not presented because findings were similar to those obtained using the above methods . The arithmetic difference in height from baseline to the end of treatment for each patient was compared between groups using a two- sample t-test and a two-way analysis of variance with the following factors : 1 ) treatment [ fluoride vs placebo ] and 2 ) fracture status ( fracture-free vs one or more new or recurrent fractures ) . For each patient , we calculated the percentage change per year for L2-L4 bone mineral content and bone density of femoral neck and radial shaft . The individual mean change for each patient was calculated as the average of yearly changes . The group mean was obtained by averaging the individual means . One- sample t-tests were then used to compare the percentage change to zero for each year or for the mean . Comparisons between groups were made using two- sample t-tests . Missing data precluded implementing a repeated- measures analysis of variance . For related adverse events , the frequency of each event was compared between the two groups by using the Fisher exact test . Adverse symptom scores were compared between the groups by using the Wilcoxon rank-sum test and within the groups by using the Wilcoxon signed-rank test . For nonvertebral fractures , the exact tests based on the binomial distribution using person-year data were used to compare the two groups . Most analyses were done using BMDP Statistical Software ( BMDP , Los Angeles , California ) . Programs for analyzing person-time data were developed by the authors . Data are presented as mean SD unless otherwise indicated . All reported P values are two-sided . Results Duration of Treatment The total duration of follow-up , including withdrawal periods , was 193 patient-years in BACKGROUND Treatment of osteoporosis following a hip fracture has been notoriously poor . Many efforts have been made to improve treatment rates . The purpose of this study was to determine whether a perioperative inpatient intervention program , involving patient education and providing a list of questions for the primary care physician , increased the percentage of patients in whom osteoporosis was addressed following a hip fracture . METHODS A prospect i ve , r and omized trial involving eighty patients who had been admitted to an academic medical center with a low-energy hip fracture was conducted . During their hospitalization , the study group patients were engaged in a fifteen-minute discussion regarding the association between osteoporosis and hip fractures , the efficacy of dual-energy x-ray absorptiometry scans in the diagnosis of osteoporosis and of bisphosphonates in its treatment , and the importance of medical follow-up for osteoporosis management . These patients were also provided with five questions regarding osteoporosis treatment to be given to their primary medical physician , and they were reminded about the questions during a follow-up telephone call six weeks later . The patients in the control group received a brochure describing methods for preventing falls . Both groups were contacted by telephone at six months after discharge to determine whether osteoporosis had been addressed . Positive indicators of intervention included assessment of bone mineral density with dual-energy x-ray absorptiometry and initiation of antiresorptive therapy .  RESULTS The average age in each group was eighty-two years , and 78 % of the patients were female . Four patients in each group did not survive through the six-month follow-up period and were excluded from the trial . Fifteen ( 42 % ) of the thirty-six patients who had been r and omized to the study group , compared with only seven ( 19 % ) of the thirty-six patients in the control group , had their osteoporosis addressed by their primary physician . This difference between the groups was significant ( p = 0.036 ) . CONCLUSIONS Patients who were provided with information and questions for their primary care physician about osteoporosis were more likely to receive appropriate therapeutic intervention than were patients who had not received the information and questions . Orthopaedic surgeons have a unique opportunity to improve the rate of osteoporosis treatment in the perioperative period following a hip fracture by educating patients and directing them toward channels for long-term osteoporosis management Summary R and omised control trial of osteoporosis screening in 4,800 women aged 45–54 years was carried out . Screened group observed an increase of 7.9 % in  hormone replacement therapy ( HRT )  use ( p < 0.001 ) , 15 % in other osteoporosis treatments ( p < 0.001 ) and a 25.9 % reduction in fracture risk compared with control . Screening for osteoporosis significantly increases treatment use and reduces fracture incidence . Introduction Population screening programmes can identify menopausal women with low bone mineral density ( BMD ) and elevated risk of future fracture but require to be proven effective by a r and omised control trial . Methods A total of 4,800 women , 45–54 years , were r and omised in equal numbers to screening or no screening ( control ) groups . Following screening , those in the lowest quartile of BMD were advised to consider HRT . Nine years later , the effect of screening on the uptake of treatment and the incidence of fractures were assessed by postal question naire . Categorical differences were assessed using χ2 test . Cox regression was used to assess hazard ratio ( HR ) . Results Of the screened and the control groups , 52.4 % vs 44.5 % , respectively , reported taking HRT ( p < 0.001 ) . In addition , 36.6 % of the screened vs 21.6 % of the control groups reported the use of vitamin D , calcium , alendronate , etidronate or raloxifene  ( p < 0.001 ) . In a per protocol analysis of verified incident fractures , a 25.9 % reduction in risk of fractures ( of any site ) in the screened group was observed ( HR = 0.741 , 95 % CI = 0.551–0.998 adjusted age , weight and height ) . Conclusions Screening for osteoporosis as assessed by low bone density significantly increases the use of HRT and other treatments for osteoporosis and reduces fracture incidence OBJECTIVE Poor adherence to therapy , perhaps related to unaddressed patient preferences , limits the effectiveness of osteoporosis treatment in at-risk women . A parallel patient-level r and omized trial in primary care practice s was performed . METHODS Eligible postmenopausal women with bone mineral density T-scores less than -1.0 and not receiving bisphosphonate therapy were included . In addition to usual primary care , intervention patients received a decision aid ( a tailored pictographic 10-year fracture risk estimate , absolute risk reduction with bisphosphonates , side effects , and out-of-pocket cost ) , and control patients received a st and ard brochure .  Knowledge transfer , patient involvement in decision-making , and rates of bisphosphonate start and adherence were studied . Data came from medical records , post-visit written and 6-month phone surveys , video recordings of clinical encounters , and pharmacy prescription profiles . RESULTS A total of 100 patients ( range of 10-year fracture risk , 6%-60 % ) were allocated r and omly to receive the decision aid ( n=52 ) or usual care ( n=48 ) . Patients receiving the decision aid were 1.8 times more likely to correctly identify their 10-year fracture risk ( 49 % vs 28 % ; 95 % confidence interval [ CI ] , 1.03 - 3.2 ) and 2.7 times more likely to identify their estimated risk reduction with bisphosphonates ( 43 % vs 16 % ; 95 % CI , 1.3 - 5.7 ) . Patient involvement improved with the decision aid by 23 % ( 95 % CI , 13.6 - 31.4 ) .  Bisphosphonates  were started by 44 % of patients receiving the decision aid and 40 % of patients receiving usual care . Adherence at 6 months was similarly high across both groups , but the proportion with more than 80 % adherence was higher with the decision aid ( n=23 [ 100 % ] vs n=14 [ 74 % ] ; P = .009 ) . CONCLUSION A decision aid improved the quality of clinical decisions about bisphosphonate therapy in at-risk postmenopausal women , did not affect start rates , and may have improved adherence CONTEXT The principle of " regression to the mean " predicts that patients with unusual responses to treatment might represent outliers who are likely to have more typical responses if treatment is continued without change . OBJECTIVE To test whether women who lose bone mineral density ( BMD ) during the first year of treatment for osteoporosis continue to lose BMD if the same treatment is continued beyond 1 year . DESIGN AND SETTING Two r and omized , double-blind , placebo-controlled trials in 11 US clinical research centers for the Fracture Intervention Trial and 180 centers in the United States and other countries for the Multiple Outcomes of Raloxifene Evaluation Trial . PARTICIPANTS AND INTERVENTIONS Postmenopausal women with low BMD assigned to treatment with 5 mg/d of alendronate sodium in the Fracture intervention Trial who completed 2 years of BMD monitoring and adhered to study medication ( n = 2634 ) , and postmenopausal women with osteoporosis assigned to treatment with 60 or 120 mg/d of raloxifene hydrochloride in the Multiple Outcomes of Raloxifene Evaluation trial who similarly completed 2 years of monitoring while adhering to study medication ( n = 3954 ) . MAIN OUTCOME MEASURES Baseline , 12- , and 24-month hip and spine BMD . RESULTS Women with the greatest loss of BMD during the first year of treatment were the most likely to gain BMD during continued treatment . Specifically , among women taking alendronate whose hip BMD decreased by more than 4 % during the first year , 83 % ( 95 % confidence interval [ CI ] , 82%-84%)had increases in hip BMD during the second year , with an overall mean increase of 4.7 % . In contrast , those who seemed to gain at least 8 % during the first year lost an average of 1 % ( 95 % CI , 0.1%-1.9 % ) during the next year . Similar results were observed among women taking raloxifene for 2 years . CONCLUSIONS Our data suggest that most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year . These results illustrate the principle of regression to the mean and suggest that effective treatments for osteoporosis should not be changed because of loss of BMD during the first year of use Introduction Older patients with fragility fractures are not commonly tested or treated for osteoporosis . Compared to usual care , a previously reported intervention led to 30 % absolute increases in osteoporosis treatment within 6 months of wrist fracture . Our objective was to examine longer-term outcomes , reproducibility , and cost-effectiveness of this intervention . Methods We conducted an extended analysis of a non-r and omized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls .  Patients > 50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta , Canada were included ; those already treated for osteoporosis were excluded . Overall , 102 patients participated in this study ( 55 intervention and 47 controls ; median age : 66 years ; 78 % were women ) . The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling . Controls received usual care ; at 6-months post-fracture , when the original trial was completed , all controls were crossed-over to intervention . The main outcomes were rates of osteoporosis testing and treatment within 6 months ( original study ) and 1 year ( delayed intervention ) of fracture , and 1-year persistence with treatments started . From the perspective of the healthcare payer , the cost-effectiveness ( using a Markov decision-analytic model ) of the intervention was compared with usual care over a lifetime horizon . Results Overall , 40 % of the intervention patients ( vs. 10 % of the controls ) started treatment within 6 months post-fracture , and 82 % ( 95%CI : 67–96 % ) had persisted with it at 1-year post-fracture . Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density ( BMD ) testing ( 64 vs. 60 % in the original study ; p = 0.72 ) and osteoporosis treatment ( 43 vs. 40 % ; p = 0.77 ) as previously reported . Compared with usual care , the intervention strategy was dominant – per patient , it led to a $ 13 Canadian ( U.S. $ 9 ) cost savings and a gain of 0.012 quality -adjusted life years . Base-case results were most sensitive to assumptions about treatment cost ; for example , a 50 % increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $ 24,250 Canadian ( U.S. $ 17,218 ) per quality -adjusted life year gained . Conclusions A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment , even when delivered 6-months post-fracture . From the healthcare payer ’s perspective , the intervention appears to have led to both cost-savings and gains in life expectancy Abstract Summary The patients ’ adherence to osteoporosis treatments is low . In our study population a history of osteoporotic fractures was associated to better compliance and persistence ; however , a 12-month r and omized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective . Purpose Several drugs are currently available for the treatment of osteoporosis , but the patients ’ compliance and persistence with these treatments are low . This study aim ed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients ( cross-sectional study ) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence ( prospect i ve study ) . Methods A total of 3379 osteoporotic patients referred as out patients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time , were enrolled for the retrospective study . Moreover , 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time , were r and omized into two groups : group 1 ( managed according to st and ard clinical practice ) and group 2 ( managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm ) . Results In the retrospective study , a history of osteoporotic fractures , the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence . Of the 816 patients enrolled in the longitudinal study , 731 ( 374 of group 1 and 357 of group 2 ) attended the 1 year follow-up visit . The percentage of women with high compliance or persistence was greater in group 2 ( 64.2 vs. 58.1 % and 66.8 vs. 62.6 % , respectively ) , but without reaching any statistical significance . Conclusions Although providing the patients with their individual fracture risk information was not statistically effective , further studies on additional interventions able to improve the patients ’ perceived risk of fracture are warranted Approximately 12 % of postmenopausal women have osteoporotic vertebral fractures ( VFs ) ; these are associated with excess morbidity and mortality and a high risk of future osteoporotic fractures . Despite this , less than one-third come to clinical attention , partly due to lack of clear clinical triggers for referral for spinal radiographs . The aim of this study was to investigate whether a novel primary care – based screening tool could be used to identify postmenopausal women with osteoporotic VFs and increase appropriate management of osteoporosis . A r and omized controlled trial was undertaken in 15 general practice s within the Bristol area of the UK . A total of 3200 women aged 65 to 80 years were enrolled , with no exclusion criteria . A simple screening tool was carried out by a nurse in primary care to identify women at high risk of osteoporotic VFs . All identified high-risk women were offered a diagnostic thoracolumbar radiograph . Radiographs were reported using st and ard National Health Service ( NHS ) reporting , with results sent back to each participant 's general practitioner ( GP ) . Participants in the control arm did not receive the screening tool or radiographs . The main outcome measure was self-reported prescription of medication for osteoporosis at 6 months with a r and om 5 % sub sample verified against electronic GP records . Secondary outcome was self-reported incidence of new fractures . Results showed that allocation to screening increased prescription of osteoporosis medications by 124 % ( odds ratio [ OR ] for prescription 2.24 at 6 months ; 95 % confidence interval [ CI ] , 1.16 to 4.33 ) . Allocation to screening also reduced fracture incidence at 12-month follow-up ( OR for new fracture 0.60 ; 95 % CI , 0.35–1.03 ; p = 0.063 ) , although this did not reach statistical significance . This study supports the use of a simple screening tool administered in primary care to increase appropriate prescription of medications for osteoporosis in postmenopausal women in the UK . © 2012 American Society for Bone and Mineral The identification of risk factors for osteoporosis has been an essential step towards the underst and ing of the onset of the disease as well as of the osteoporosis-related fractures due to bone fragility . The present study has been aim ed at assessing whether a correlation may exist between the increment in bone mass , consequent to an antiresorption therapy , and the reduction in the incidence of fractures . Moreover , the possibility that such a reduction might result from the action of other factors , such as the changes in bone microstructure , has been investigated . A total of 2,000 osteoporotic women ( mean age : 68 + /- 9 years ) were enrolled in the study and divided at r and om into 4 treatment groups . Each group received one of the following treatments : Alendronate 10 mg/daily ( 1,000 patients ) , Clodronate 100 mg/weekly i.m . ( 800 patients ) , Risedronate 5 mg/dailt ( 100 patients ) , and Raloxifene 60 mg/daily ( 100 patients ) . Clinical evaluation was based on bone mineral density ( BMD ) assay on lumbar vertebrae ( L1-L4 ) by means of a DEXA ( Lunar DPX ) mineralometer , as well as on the incidence of fractures following both 12- and 24-month treatment periods . The results showed an overlapping pattern in patients treated with Alendronate or Risedronate , namely a significant increment in BMD after a 24-month treatment period , whereas such an increment in BMD was less evident in patients receiving either Clodronate or Risedronate after a 24-month treatment period . In addition , a total of 18 osteoporosis-related fractures were observed during the entire study period ; 10 out of 18 fractures occurred in the Alendronate treated group , whereas the remaining 8 fractures were observed in the Clodronate treated group . Fourteen fractures were detected in patients over 80-year old , whereas the remaining 4 occurred in patients aged from 70 to 79 years and appeared to be independent of both the T-score assigned and the BMD increment obtained as a result of the therapy . Such findings suggest that the plain monitoring of BMD appears not to be adequate to anticipate clearly the danger of the probable onset of additional fractures , while the higher incidence of fractures in patients over 80-year old evidence s that " old age " has to be considered the most serious risk factor for osteoporosis , since it is also the real responsible factor for changes taking place in bone microstructure Background Bisphosphonates can reduce fracture risk in patients with osteoporosis , but many at-risk patients do not start or adhere to these medications . The aims of this study are to : ( 1 ) preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid ( OSTEOPOROSIS CHOICE ) for postmenopausal women at risk for osteoporotic fractures ; and ( 2 ) assess the feasibility and validity ( i.e. , absence of contamination ) of patient-level r and omization ( vs. cluster r and omization ) in pilot trials of decision aid efficacy . Methods / Design This is a protocol for a parallel , 2-arm , r and omized trial to compare an intervention group receiving OSTEOPOROSIS CHOICE to a control group receiving usual primary care .  Postmenopausal women with bone mineral density T-scores of < -1.0 , not receiving bisphosphonate therapy , and receiving care at participating primary care practice s in and around Rochester , Minnesota , USA will be eligible to participate in the trial . We will measure the effect of OSTEOPOROSIS CHOICE on five outcomes : ( a ) patient knowledge regarding osteoporosis risk factors and treatment ; ( b ) quality of the decision-making process for both the patient and clinician ; ( c ) patient and clinician acceptability and satisfaction with the decision aid ; ( d ) rate of bisphosphonate use and adherence , and ( e ) trial processes ( e.g. , ability to recruit participants , collect patient outcomes ) . To capture these outcomes , we will use patient and clinician surveys following each visit and video recordings of the clinical encounters . These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients ( i.e. , contamination ) . Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months . Discussion This pilot trial will provide evidence of feasibility , validity of patient r and omization , and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures . The results will inform the design of a larger trial that could provide more precise estimates of the efficacy of the decision aid . Trial registration Clinical Trials.gov Identifier : Summary Few out patients with fractures are treated for osteoporosis in the years following fracture . In a r and omized pilot study , we found a nurse case-manager could double rates of osteoporosis testing and treatment compared with a proven efficacious quality improvement strategy directed at patients and physicians ( 57 % vs 28 % rates of appropriate care ) . Introduction Few patients with fractures are treated for osteoporosis . An intervention directed at wrist fracture patients ( education ) and physicians ( guidelines , reminders ) tripled osteoporosis treatment rates compared to controls ( 22 % vs 7 % within 6 months of fracture ) . More effective strategies are needed . Methods We undertook a pilot study that compared a nurse case-manager to the multifaceted intervention using a r and omized trial design . The case-manager counseled patients , arranged bone mineral density ( BMD ) tests , and prescribed treatments . We included controls from our first trial who remained untreated for osteoporosis 1-year post-fracture . Primary outcome was  bisphosphonate treatment and secondary outcomes were BMD testing , appropriate care ( BMD test-treatment if bone mass low ) , and costs . Results Forty six patients untreated 1-year after wrist fracture were r and omized to case-manager ( n = 21 ) or multifaceted intervention ( n = 25 ) . Median age was 60 years and 68 % were female . Six months post-r and omization , 9 ( 43 % ) case-managed patients were treated with bisphosphonates  compared with 3 ( 12 % ) multifaceted intervention patients ( relative risk [ RR ] 3.6 , 95 % confidence intervals [ CI ] 1.1–11.5 , p = 0.019 ) . Case-managed patients were more likely than multifaceted intervention patients to undergo BMD tests ( 81 % vs 52 % , RR 1.6 , 95%CI 1.1–2.4 , p = 0.042 ) and receive appropriate care ( 57 % vs 28 % , RR 2.0 , 95%CI 1.0–4.2 , p = 0.048 ) . Case-management cost was $ 44 ( CDN ) per patient vs $ 12 for the multifaceted intervention . Conclusions A nurse case-manager substantially increased rates of appropriate testing and treatment for osteoporosis in patients at high-risk of future fracture when compared with a multifaceted quality improvement intervention aim ed at patients and physicians . Even with case-management , nearly half of patients did not receive appropriate care . Trial Registry clinical trials.gov identifier : Context Few studies have evaluated the relative effectiveness of drug therapies for osteoporosis . Contribution This study compared nonvertebral fractures that occurred within 1 year of initiating osteoporosis pharmacotherapy among 43135 enrollees in 2 statewide pharmaceutical benefit programs . Differences in fracture risk between adults prescribed risedronate or raloxifene and those prescribed  alendronate  were small . Fracture risk seemed to be higher with calcitonin than alendronate . Caution Wide confidence bounds around risk estimates did not rule out potentially important differences between some agents . No adherence data were available , and the ability to account for confounders was limited . Implication There probably is no single clearly superior drug therapy for osteoporosis . The Editors Osteoporosis is characterized by decreased bone mass and deterioration of bone tissue , result ing in reduced bone strength and increased fracture risk ( 1 , 2 ) . Approved therapies for osteoporosis include bisphosphonates , calcitonin , raloxifene , and teriparatide . Findings from r and omized , controlled , head-to-head trials show that women who received alendronate have greater gains in bone mineral density and greater reductions in bone turnover markers within 12 and 24 months of initiation than those who received risedronate ( 3 , 4 ) or raloxifene ( 57 ) . Although bone mineral density is a strong predictor of fracture ( 8) , differences in these surrogate markers may not translate into appreciable differences in fracture risk ( 911 ) . Results from observational studies suggest that risedronate may reduce the risk for nonvertebral fracture ( clavicle , hip , humerus , leg , pelvis , and wrist ) within 12 months more effectively than alendronate or nasal calcitonin ( 12 , 13 ) . To our knowledge , no studies have compared the relative effectiveness of raloxifene versus bisphosphonates or calcitonin in reducing fracture risk . Further comparative effectiveness studies may help to clarify the relative effectiveness of osteoporosis treatments ( 14 ) . We completed a population -based study of new recipients of oral bisphosphonates ( alendronate or risedronate ) , nasal calcitonin , and raloxifene to compare the relative effectiveness of these agents in reducing nonvertebral fracture risk . Methods Study Cohort The study population comprised Medicare beneficiaries enrolled in 2 statewide pharmaceutical benefit plans : the New Jersey Pharmaceutical Assistance to the Aged and Disabled program and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly . These programs provide drug coverage without restriction for low-income residents age 65 years or older with minimal copayment . Our cohort consisted of new recipients ( no use of any of these agents in the previous year ) of oral bisphosphonates ( alendronate , 10 mg or 70 mg , or risedronate , 5 mg or 35 mg ) , nasal calcitonin , or raloxifene  between 1 April 2000 and 30 June 2005 ( Figure 1 ) . To ensure complete plan coverage , study eligibility was limited to patients with 1 or more cl aims in both Medicare and their state pharmaceutical assistance plan in each of the three 6-month intervals preceding the index prescription . We excluded nursing home residents ( for whom prescription data may not be complete ) , patients with a Medicare cl aim for Paget disease ( International Classification of Diseases , Ninth Revision , Clinical Modification code 731.0 ) , and patients with pharmacy cl aims indicating receipt of any bisphosphonate or teriparatide in the year before treatment initiation . Our data included all Medicare beneficiaries from the 2 plans that met eligibility criteria ; we did not do formal sample size calculations . We restricted inclusion to the period when all drugs were available : that is , 1 April 2000 ( risedronate received U.S. Food and Drug Administration approval in April 2000 ) . At the time of analysis , we had complete Medicare data from 1 April 2000 to 31 December 2003 for New Jersey and from 1 April 2000 to 31 December 2005 for Pennsylvania . Figure 1 . Study flow diagram . Osteoporosis drugs were oral bisphosphonates ( alendronate , 10 mg or 70 mg ; risedronate , 5 mg or 35 mg ) , nasal calcitonin , or raloxifene . * May meet > 1 exclusion criterion . Outcomes Our primary outcome of interest was nonvertebral fracture within 12 months of treatment initiation . We defined nonvertebral fracture as a fracture of the hip , humerus , or radius or ulna by using previously vali date d criteria requiring diagnostic and procedural codes from Medicare cl aims ( 15 ) . When medical records are used as the reference st and ard , the estimated sensitivity of each outcome is at least 90 % ( 15 ) . Secondary outcomes included nonvertebral fractures within 6 and 24 months of treatment initiation and hip fracture within 6 , 12 , and 24 months of treatment initiation . Covariates Patient demographic characteristics were determined at treatment initiation and other variables by medical and pharmacy cl aims within the year before treatment initiation . We considered covariates that were plausibly related to our fracture outcomes ( 16 ) : demographic characteristics ( age , sex , race ) , osteoporosis-related factors ( such as diagnosis of osteoporosis , fracture history ) , relevant comorbid conditions ( such as comorbidity score [ 17 , 18 ] ; diabetes mellitus ; history of falls , syncope , and gait abnormalities ; cancer ; rheumatoid arthritis ) , drug use ( such as antiepileptics , -blockers , benzodiazepines , glucocorticoids , hormone therapy , selective serotonin reuptake inhibitors , thiazide diuretics , number of drugs ) , and previous hospitalization . We also included calendar time ( month and year ) of the index prescription to adjust for potential secular trends in prescribing . Appendix Table 1 lists all variables , definitions , and coding . If a record of a specific diagnosis , procedure , or prescription was lacking , patients were coded as not having these characteristics . As a result of this coding rule , there were no participants for whom exposure , confounder , or outcome information was missing . However , race was unknown in 41 patients . These 41 missing data points were recoded as Caucasian . Appendix Table 1 . Definition and Coding of Variables Included in Multinomial Logistic Regression Model Used to Create Propensity Scores Statistical Analysis We calculated fracture rates among recipients of each drug within 6 , 12 , and 24 months of treatment initiation . We used KaplanMeier methods to plot cumulative fracture incidence and Cox proportional hazard models to compare fracture rates between agents . In our primary analysis , we considered a patient exposed to drug throughout follow-up by censoring only at date of death or end of follow-up ( hereafter referred to as intent-to-treat analysis , an analogue of intention-to-treat analysis ) . We tested proportional hazard assumptions by using interaction terms between exposures and time and found no violations for the primary analysis of 12-month follow-up . However , we observed a violation result ing in an attenuated effect for raloxifene over 24 months . This observation is expected when an intent-to-treat scenario is assumed because adherence to osteoporosis pharmacotherapy is suboptimal ( 19 , 20 ) . Similar attenuation of effects was also observed when hip fracture was the outcome . We developed propensity scores for each drug by using multinomial logistic regression ( 21 ) . Alendronate , the most commonly prescribed osteoporosis treatment , was selected as the reference category . To account for baseline differences between New Jersey and Pennsylvania , we derived state-specific propensity scores and stratified all adjusted Cox proportional hazard models by state . Propensity score quintiles for risedronate , calcitonin , and raloxifene were included as 12 dummy variables ( 4 for each drug ) to adjust for confounding ( 2124 ) . We summarized the balance achieved within state-specific propensity score quintiles into descriptive tables and examined the magnitude of difference for each covariate within each propensity score quintile . Preliminary examination suggested residual imbalance within some quintiles ( Appendix Tables 2 and 3 ) . For example , within the lowest propensity score quintile for receipt of raloxifene in New Jersey ( Appendix Table 2 ) , 76 % of patients who received alendronate and 87 % of patients who received raloxifene had a background prevalence of osteoporosis . Therefore , we included age groups , fracture history , race , and diagnosis of osteoporosis , in addition to propensity score quintiles , in our adjusted regression models . Analyses were performed with SAS software , version 9.1 ( SAS Institute , Cary , North Carolina ) . Appendix Table 2 . Propensity Score Quintiles : New Jersey * Appendix Table 3 . Propensity Score Quintiles : Pennsylvania * We used sensitivity analysis to examine the robustness of our findings . First , we examined outcomes assuming an on-treatment scenario . We censored patients on the first day of switching agents , losing drug plan eligibility , entering a nursing home , or discontinuing drug therapy ( last date covered by drug plus 15 days , allowing for 30-day gaps between prescriptions ) , on the day of death , or at the end of follow-up ( 12 months , 31 December 2003 [ New Jersey ] , or 31 December 2005 [ Pennsylvania ] ) . Second , we extended the days that patients received therapy in our on-treatment scenario to the last date covered by drug plus 90 days . Third , we examined several different subgroups : history of any fracture ( International Classification of Diseases , Ninth Revision , Clinical Modification codes 733.1x and 800.xx through 829.xx ) within the year before treatment initiation , no fracture history , at least 2 consecutive prescriptions of their index drug , no known history of malignant neoplasm , osteoporosis diagnosis , no diagnosis of osteoporosis , and women with no previous hormone therapy . Fourth , given that the main risk factors for fracture measurable in our data set are previous fracture and age , we compared fracture rates stratified by Background Osteoporosis-related fractures are a significant public health concern . Interventions that increase detection and treatment of osteoporosis are underutilized . This pragmatic r and omised study was done to evaluate the impact of a multifaceted community-based care program aim ed at optimizing evidence -based management in patients at risk for osteoporosis and fractures . Methods This was a 12-month r and omized trial performed in Ontario , Canada . Eligible patients were community-dwelling , aged ≥55 years , and identified to be at risk for osteoporosis-related fractures . Two hundred and one patients were allocated to the intervention group or to usual care . Components of the intervention were directed towards primary care physicians and patients and included facilitated bone mineral density testing , patient education and patient-specific recommendations for osteoporosis treatment . The primary outcome was the implementation of appropriate osteoporosis management . Results 101 patients were allocated to intervention and 100 to control . Mean age of participants was 71.9 ± 7.2 years and 94 % were women . Pharmacological treatment ( alendronate , risedronate , or raloxifene ) for osteoporosis was increased by 29 % compared to usual care ( 56 % [ 29/52 ] vs. 27 % [ 16/60 ] ; relative risk [ RR ] 2.09 , 95 % confidence interval [ CI ] 1.29 to 3.40 ) . More individuals in the intervention group were taking calcium ( 54 % [ 54/101 ] vs. 20 % [ 20/100 ] ; RR 2.67 , 95 % CI 1.74 to 4.12 ) and vitamin D ( 33 % [ 33/101 ] vs. 20 % [ 20/100 ] ; RR 1.63 , 95 % CI 1.01 to 2.65 ) . Conclusions A multi-faceted community-based intervention improved management of osteoporosis in high risk patients compared with usual care . Trial Registration This trial has been registered with clinical trials.gov ( ID : NCT00465387 BACKGROUND Despite effective assessment methods and medications targeting osteoporosis and related fractures , screening for fracture risk is not currently advocated in the UK . We tested whether a community-based screening intervention could reduce fractures in older women . METHODS We did a two-arm r and omised controlled trial in women aged 70 - 85 years to compare a screening programme using the Fracture Risk Assessment Tool ( FRAX ) with usual management . Women were recruited from 100 general practitioner ( GP ) practice s in seven regions of the UK : Birmingham , Bristol , Manchester , Norwich , Sheffield , Southampton , and York . We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study ( eg , known dementia , terminally ill , or recently bereaved ) . The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period . In the screening group , treatment was recommended in women identified to be at high risk of hip fracture , according to the FRAX 10-year hip fracture probability . Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture , any clinical fracture , or mortality ; and the effect of screening on anxiety and health-related quality of life . This trial is registered with the International St and ard R and omised Controlled Trial registry , number IS RCT N 55814835 . FINDINGS 12 483 eligible women were identified and participated in the trial , and 6233 women r and omly assigned to the screening group between April 15 , 2008 , and July 2 , 2009 . Treatment was recommended in 898 ( 14 % ) of 6233 women . Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls ( 15 % vs 4 % ) , with uptake particularly high ( 78 % at 6 months ) in the screening high-risk subgroup . Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures ( hazard ratio [ HR ] 0·94 , 95 % CI 0·85 - 1·03 , p=0·178 ) , nor the overall incidence of all clinical fractures ( 0·94 , 0·86 - 1·03 , p=0·183 ) , but screening reduced the incidence of hip fractures ( 0·72 , 0·59 - 0·89 , p=0·002 ) . There was no evidence of differences in mortality , anxiety levels , or quality of life . INTERPRETATION Systematic , community-based screening programme of fracture risk in older women in the UK is feasible , and could be effective in reducing hip fractures . FUNDING Arthritis Research UK and Medical Research Council
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 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 .