A systematic review of the effectiveness of interventions to improve post-fracture investigation and management of patients at risk of osteoporosis Effects of pharmaceutical care on adherence and persistence to bisphosphonates in postmenopausal osteoporotic women. Five years of anti-resorptive activity after a single dose of zoledronate--results from a randomized double-blind placebo-controlled trial. Effect of raloxifene combined with monofluorophosphate as compared with monofluorophosphate alone in postmenopausal women with low bone mass: a randomized, controlled trial Appropriate use of anabolic treatment for severe osteoporosis. The care gap in diagnosis and treatment of women with a fragility fracture The impact of monitoring on adherence and persistence with antiresorptive treatment for postmenopausal osteoporosis: a randomized controlled trial. Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis: implications of improved persistence with less frequently administered oral bisphosphonates Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis. Use of Calcium Supplements, Vitamin D Supplements and Specific Osteoporosis Drugs Among French Women Aged 75–85 Years: Patterns of Use and Associated Factors Monitoring of bone turnover markers does not improve persistence with ibandronate treatment. Improvement in the Undertreatment of Osteoporosis Following Hip Fracture Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. Evaluation of a Nationwide Pharmacist-Led Phone Outreach Program to Improve Osteoporosis Management in Older Women with Recently Sustained Fractures. Adherence and persistence in patients with severe osteoporosis treated with teriparatide Risedronate decreases bone resorption and improves low back pain in postmenopausal osteoporosis patients without vertebral fractures Clinical use of denosumab for the treatment for postmenopausal osteoporosis Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal osteoporotic women treated with risedronate. Assessment of adherence to treatment of postmenopausal osteoporosis with raloxifene and/or alfacalcidol in postmenopausal Japanese women Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case-control analysis. Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women.
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 WHAT IS KNOWN AND OBJECTIVE Studies have shown that comprehensive interventions by pharmacists can improve adherence and persistence to osteoporosis therapy , but the association between adherence and bone turnover markers ( BTMs ) has never been studied . Therefore , the aim of this study was to evaluate the effects of pharmaceutical care on medication adherence ( and its effects on BTMs ) , as well as persistence of postmenopausal osteoporotic women to prescribed bisphosphonates . METHODS A r and omized controlled trial was conducted from 2005 to 2009 in the University Malaya Medical Centre , Malaysia . INCLUSION CRITERIA postmenopausal osteoporotic women diagnosed with osteoporosis with a T-score ≤ -2·5 or who had a low-trauma fracture and prescribed weekly alendronate/risedronate .  Intervention participants received counselling on osteoporosis , risk factors , lifestyle modifications , goals of therapy , side effects and the importance of adherence . Adherence was assessed at months 3 , 6 and 12 , and persistence at month 12 . Feedback on BTMs was provided at months 4 and 7 . The control group received no counselling . Two BTMs were used : serum C-terminal cross-linking telopeptide of type I collagen ( CTX-I ) and serum osteocalcin ( OC ) . MAIN OUTCOMES MEASURED medication adherence , BTMs and persistence . RESULTS AND DISCUSSION Intervention participants who received pharmaceutical care reported significantly higher medication adherence at 6 ( P = 0·015 ) and 12 months ( P = 0·047 ) compared with the control group ; but this effect was not shown by the BTMs . This is probably due to the long effect of bisphosphonates in bone . A significant difference was found between serum CTX-I and OC in identifying non-responders to anti-resorptive therapy ( P < 0·001 ) , indicating the usefulness of BTMs as an objective marker . However , pharmaceutical care did not affect persistence to osteoporosis therapy within a 1-year period [ log rank ( Mantel-Cox ) χ² = 0·496 , P = 0·481 ] . The proportion of participants who were persistent with bisphosphonate therapy after 12 months was 89·8 % and 87·0 % in the control and intervention group respectively . WHAT IS NEW AND CONCLUSION The provision of pharmaceutical care improved medication adherence but not persistence . BTMs were not appropriate objective measures for assessing adherence to weekly bisphosphonates but were useful for identifying non-responders to treatment within 3 - 6 months , much earlier than using bone mineral density . The study indicates that pharmacists have a role in improving medication adherence , but its long-term effect on persistence warrants further studies with longer duration Intravenous zoledronate 5 mg , administered annually , prevents fractures in people with osteoporosis , but the optimal dosing schedule is not known . Previously , we reported that a single dose of 5 mg zoledronate stably decreased bone turnover and increased bone mineral density ( BMD ) for 3 years in a r and omized controlled trial in 50 postmenopausal women with osteopenia . We have now completed a 2-year double-blind extension of this trial , during which no additional treatment was administered . The primary endpoint was change in the bone turnover markers procollagen type-I N-terminal propeptide ( P1NP ) and β-C-terminal telopeptide of type I collagen ( β-CTX ) ; the secondary endpoint was change in BMD at lumbar spine , total hip and total body . Mean levels of the each of the bone turnover markers were lower in the zoledronate group throughout the study ( P<0.0001 for each marker ) . After 5 years , mean ( 95 % CI ) levels of β-CTX and P1NP were 277 ng/L ( 150 , 404 ) and 28 μg/L ( 16 , 40 ) lower in the zoledronate group , corresponding to reductions of 48 % and 45 % , respectively . BMD was higher in the zoledronate group during the study ( P<0.0001 for each site ) . After 5 years , BMD in the zoledronate group was higher by 4.2 % ( 1.1 , 7.2 ) at the lumbar spine , by 5.3 % ( 2.7 , 7.9 ) at the total hip , and by 2.7 % ( 1.1 , 4.2 ) at the total body . These findings suggest that the anti-resorptive effects of a single 5 mg dose of zoledronate persist for at least 5 years in postmenopausal women . Trials assessing the anti-fracture efficacy of dosing intervals of zoledronate of up to 5 years are justified Raloxifene effectively reduces the incidence of vertebral fractures in patients with postmenopausal osteoporosis . Recent data suggest that low-dose monofluorophosphate ( MFP ) plus calcium reduces the vertebral fracture rate in postmenopausal women with moderate osteoporosis . The objective of this study was to evaluate the combination of raloxifene and MFP in the treatment of postmenopausal women with osteopenia , osteoporosis and severe osteoporosis . A total of 596 postmenopausal women with osteopenia , osteoporosis and severe osteoporosis ( mean femoral neck T-score of –2.87 SD ) were r and omized to treatment with 60 mg/day raloxifene HCl and 20 mg/day fluoride ions ( as MFP ) or 20 mg/day fluoride and placebo for 18 months . All patients received calcium ( 1000 mg/day ) and vitamin D ( 500 IU/day ) supplements . Changes in bone mineral density ( BMD ) , as primary endpoint , and the rate of osteoporotic fractures and biochemical markers , as secondary endpoints , were assessed . As compared with MFP , raloxifene plus MFP was associated with significantly greater mean increases in the BMD of the femoral neck ( 1.37 % versus 0.33 % ; P=0.004 ) , total hip ( 0.89 % versus −0.42 % ; P<0.001 ) and lumbar spine ( 8.80 % versus 5.47 % P<0.001 ) . In the raloxifene plus MFP group , 16 patients sustained 17 osteoporotic fractures , as compared with 22 patients sustaining 34 incident osteoporotic fractures in the MFP group ( P=0.313 ) . One patient in the raloxifene plus MFP group sustained multiple osteoporotic fractures , as compared with eight patients in the MFP group ( P=0.020 ) . MFP alone significantly increased the serum bone alkaline phosphatase ( bone ALP ) and the urinary C-terminal crosslinking telopeptide of type I collagene ( U-CTX ) . The addition of raloxifene in the combination arm blunted the rise in bone ALP , which remained nevertheless significant , and abolished the increase in U-CTX . The combination of raloxifene with MFP was generally well tolerated . This study demonstrates that , in postmenopausal women with osteopenia , osteoporosis and severe osteoporosis , the combination therapy of raloxifene plus MFP favorably influences the BMD and the bone formation and resorption balance , and may reduce the risk of multiple osteoporotic fractures compared to MFP alone 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 Summary In women aged 50 years or more who experienced a fracture , 81 % suffered a fragility fracture . Six to eight months after fragility fracture , 79 % had either not been investigated for osteoporosis or prescribed anti-fracture therapy . Despite fragility fractures being common in this population osteoporosis is under-diagnosed and under-treated . Introduction The objective of this study was to evaluate the diagnostic and treatment rates for osteoporosis six months following fragility fracture . Methods This prospect i ve cohort study was set in the general community from the Province of Quebec , Canada . Women at least 50 years of age who suffered a fracture were recruited during their initial visit to the hospital and had their fracture type classified as either fragility or traumatic . Six-to-eight months after fragility fracture , women were again contacted to evaluate the diagnostic and treatment rates of osteoporosis .  Results Of the 2,075 women recruited over a 25 month period 1688 ( 81 % ) sustained a fragility fracture and 387 ( 19 % ) sustained a traumatic fracture . Nine hundred and three participants with a fragility fracture were again contacted six-to-eight months after fracture . For the 739 women not on treatment on the recruitment day , only 15.4 % initiated pharmacological therapy in the six-to-eight-month period following fracture and 79.0 % had either not been investigated for osteoporosis or prescribed anti-fracture treatment . Conclusions The proportion of fragility fractures to total fractures is higher than previously reported . Despite the availability of diagnostic modalities , effective treatments , and adequate health care assessment s , there is a substantial care gap in the management of osteoporosis 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 ABSTRACT Objective : Studies have shown that weekly bisphosphonate dosing results in improved persistence compared to daily dosing among patients with postmenopausal osteoporosis , yet more than 50 % of patients discontinue therapy within a year . An oral , less frequent administration bisphosphonate provides an opportunity to improve persistence , a parameter not well modeled in previous cost-effectiveness analyses of osteoporosis therapies . Research design and methods : We developed a Markov model to estimate the effect of improved persistence on the cost-effectiveness of bisphosphonates among postmenopausal women with established osteoporosis ( vertebral fracture and bone mineral density T-score ≤ –2.5 ) and an average age of 78 years .  Fracture risks , clinical efficacy , mortality , re source use , costs , and utilities were obtained from the published literature . Persistence rates were derived primarily from a published clinical trial . Approximately 50 % greater persistence with a monthly versus a weekly therapy was assumed on the basis of the PERSIST study , a 6-month , r and omized , head-to-head prospect i ve study that investigated treatment persistence in postmenopausal osteoporotic women on monthly versus weekly bisphosphonate therapy . Persistence was extrapolated to a maximum of 5 years . Following discontinuation , treatment benefit declined linearly and proportionally to the duration of active treatment . Results : Based on model estimates , more fractures were avoided ( versus no treatment ) with monthly bisphosphonate ( 58.1 per 1000 treated women ) than with weekly bisphosphonates ( 33.8 per 1000 treated women ) , result ing in lower fracture care costs per woman ( $ 7317 and $ 7548 , respectively ) . The incremental cost per quality -adjusted life-year gained was lower with a monthly bisphosphonate ( $ 13 749 ) than with weekly bisphosphonates ( $ 16 657 ) when compared to no treatment . The incremental cost per quality -adjusted life-year of a monthly bisphosphonate was $ 9476 when compared to a weekly bisphosphonate . Conclusions : In postmenopausal women with established osteoporosis , improvement in persistence with a less frequently administered oral bisphosphonate therapy could augment the fracture benefit and thereby improve cost-effectiveness . Further studies are required to refine the estimates of cost-effectiveness in order to address limited availability of adherence and fracture risk data Background Adherence to anti-osteoporosis treatments is poor , exposing treated women to increased fracture risk . Determinants of poor adherence are poorly understood . The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance . Methods This was an observational , cross-sectional pharmacoepidemiological study with a r and omly-selected sample of 420 GPs , 154 rheumatologists and 110 gynaecologists practicing in France . Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months . Investigators completed a question naire on clinical features , treatments and medical history , and on patient compliance . Patients completed a question naire on sociodemographic features , lifestyle , attitudes and knowledge about osteoporosis , treatment compliance , treatment satisfaction and quality of life .  Treatment compliance was evaluated with the  Morisky Medication-taking Adherence Scale . Variables collected in the question naires were evaluated for association with compliance using multivariate logistic regression analysis . Results 785 women were evaluated . Physicians considered 95.4 % of the sample to be compliant , but only 65.5 % of women considered themselves compliant . The correlation between patient and physician perceptions of compliance was low ( κ : 0.11 [ 95 % CI : 0.06 to 0.16 ] ) . Patient-rated compliance was highest for monthly bisphosphonates ( 79.7 % ) and lowest for hormone substitution therapy ( 50.0 % ) . Six variables were associated with compliance : treatment administration frequency , perceptions of long-term treatment acceptability , perceptions of health consequences of osteoporosis , perceptions of knowledge about osteoporosis , exercise and mental quality of life . Conclusion Compliance to anti-osteoporosis treatments is poor . Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience . Ib and ronate is a highly potent nitrogen-containing bisphosphonate , proven to significantly increase vertebral and nonvertebral bone mineral density ( BMD ) when administered as a convenient intravenous injection . A recent double-blind , placebo-controlled , r and omized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ib and ronate injections , given once every 3 months , in 2862 women ( 55 - 76 years ) with postmenopausal osteoporosis [ one to four prevalent vertebral fractures and lumbar spine ( L1-L4 ) BMD T score of less than -2.0 and greater than -5.0 in > or=1 vertebra ] . All participants received daily vitamin D ( 400 IU ) and calcium ( 500 mg ) supplementation . The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years . However , although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo ( 9.2 % vs. 8.7 % vs. 10.7 % in the 1 mg , 0.5 mg and placebo groups , respectively ) , as well as in the incidence of nonvertebral and hip fractures , the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance . At the studied doses , intravenous ib and ronate injections also produced dose-dependent , but comparatively small , increases in lumbar spine BMD ( 4.0 % and 2.9 % , respectively ) and decreases in biochemical markers of bone resorption and formation , relative to placebo .  Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover . In light of the clear dose-response relationship observed in this and other studies , this is likely to be achieved with higher intravenous doses of ib and ronate . The results of a recent phase II/III study ( Intermittent Regimen Intravenous Ib and ronate Study : the IRIS study ) provide support for this hypothesis Background Despite the availability of effective preventive and curative medications for osteoporosis , and guidelines for its diagnosis and management , few individuals are treated for osteoporosis , even among those who have already had a fracture . Objectives Our objective was to describe the patterns of use of medication for osteoporosis , i.e. , calcium supplements , vitamin D supplements , and specific anti-osteoporotic drugs , such as bisphosphonates , in a large sample of French older women living at home , and to identify individual factors associated with use of these medications overall and in two specific clinical situations . Methods Cross-sectional analysis of data from 4,221 women aged 75–85 years who participated in a balance and mobility examination as part of the screening procedure for the Ossébo study , a r and omized controlled trial testing the effectiveness of exercise for the prevention of fall-related injuries .  Electoral rolls  were used to invite women in 16 towns to participate ( participation rate 10.3 % ) . Information collected through question naires included current medication use and , in particular , use of osteoporosis medications ( specific osteoporosis drugs , calcium and vitamin D supplementation ) in the past 6 months , and history of fracture since the age of 50 , including fracture locations . Fractures were categorized in three groups : no fracture , major osteoporotic fracture ( hip , humerus , wrist , pelvis , and vertebra ) , and other fracture . Results Nearly 48 % of the participants reported they did not take calcium or vitamin D supplements or any specific  osteoporosis drugs  . Of the 2,133 women who reported using osteoporosis medication , 85 % used  vitamin D supplements ( 25 % as the sole medication against this disease ) , 59 % calcium supplements , and 42 % a specific anti-osteoporotic drug ( 75 % of them combining it with vitamin D supplementation ) . The use of any osteoporosis medication was significantly associated ( p < 0.001 ) with a history of a major osteoporotic fracture , lower weight , dual-energy X-ray absorptiometry ( DXA ) bone-density measurement in the past 5 years , a cancer-screening examination in the past 5 years , and a positive attitude toward medication use in general . Living alone was associated with a lower likelihood of using a specific anti-osteoporotic drug  , and a higher education level was associated with a higher likelihood of vitamin D supplementation . Of the 1,553 women who had already had a major osteoporotic fracture , one-third ( 34.8 % ) were not taking any osteoporosis medication . In this subgroup , use of this medication was associated with the same factors as in the overall study population . In particular , neither older age nor a history of falls in the previous 12 months was associated with a higher likelihood of using osteoporosis medication . Among the 909 women who reported using a specific osteoporosis drug , vitamin D use was associated with a higher educational level and a more frequent preventive attitude . Conclusion In France , as in other western countries , women aged 75 years and over are not managed according to guidelines . Further studies should address the barriers encountered in improving quality of care in osteoporosis management OBJECTIVE To assess if the use of biological marker of bone resorption ( CTX ) feedback is a mean to improve persistence on monthly oral ib and ronate . METHODS One year prospect i ve multicenter study using a cluster r and omisation design with physicians as r and omized units into two groups , A and B ; in group B , physicians used results of CTX and two st and ardized messages according to CTX changes from baseline : suboptimal if decrease less than 30 % at week 6 , positive otherwise . In group A , the follow-up was st and ard of care . Patients were postmenopausal women , initiating a treatment with ib and ronate 150 mg monthly . They were blinded to the study hypotheses and outcome . The outcome was the proportion of patients persistent at 1-year visit . RESULTS Eighty-eight physicians were r and omized in group A and included 346 patients , 75 in group B included 250 patients . The persistence at 1-year was high and not different between the two groups ( 75.1 and 74.8 % P=0.932 ) . There was no difference in the proportion of persistent patients according to the message delivered in the group of patient with CTX information : 77.4 and 74.8 % in patients with a suboptimal or positive message respectively . CONCLUSION This study failed to demonstrate that supporting monitoring of CTX could improve persistence to ib and ronate treatment in postmenopausal osteoporosis . KEY MESSAGES Persistence is a strong determinant of anti-osteoporotic treatments efficacy . Monitoring of bone markers is not a mean to improve persistence of an oral bisphosphonate . There is a discrepancy between levels of persistence in clinical studies and real life Background : Osteoporosis is a common disease characterized by decreased bone mass and increased fracture risk in postmenopausal women and the elderly . Hip fractures are among the most common consequences of osteoporosis and unfortunately usually occur late in the course of the disease . When a patient is admitted to the hospital with a fragility hip fracture , a unique opportunity for diagnosis and treatment presents itself . Fortunately , several medications have proven to be effective in lowering the risk of future fractures . The purpose s of the present study were to test the hypothesis that most fragility hip fractures go untreated and to determine whether educational efforts to raise physician awareness have led to an improvement in osteoporosis treatment rates . Methods : A retrospective cohort study was performed with use of the patient data bases at two university medical centers and one university-affiliated community hospital . The charts of 300 r and omly selected patients were sorted with use of ICD-9 ( International Classification of Diseases , Ninth Revision ) codes for femoral neck fractures . There were 100 patients from each center , with twenty-five patients from each year between 1997 and 2000 . The admitting diagnosis , mechanism of injury , admission medications , procedures performed during hospitalization , and discharge medications were then extracted and analyzed . During this period , the National Osteoporosis Foundation established guiding principles for the treatment of fragility fractures . Results : Of the seventy-five patients from all centers for each year from 1997 to 2000 , 11 % , 13 % , 24 % , and 29 % , respectively , were discharged with a prescription for some medication targeting osteopenia , either supplemental calcium or an antiosteoporotic medication ( estrogen , calcitonin , a bisphosphonate , or raloxifene ) . A trended chi-square analysis of this increase revealed a p value of < 0.001 , indicating that this improvement in treatment was unlikely due to chance alone . Fifty-eight ( 19.3 % ) of the 300 patients in the study received a prescription at the time of discharge . However , forty of these patients ( 13.3 % of the overall group ) received calcium  and only eighteen ( 6.0 % of the overall group ) received a medication to actively prevent bone resorption and treat osteoporosis . In addition , no patient underwent a bone density scan while in the hospital . Conclusions : Elderly patients and postmenopausal women who are admitted to the hospital and diagnosed with a low-energy femoral neck fracture have been undertreated for osteoporosis . However , over the four years of the present study , there was a significant increase in the rate of treatment . It is hoped that treatment rates will continue to increase in the future with continued educational efforts Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation . We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate , a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity . The patients were r and omly assigned in equal numbers to receive oral etidronate ( 400 mg per day ) or placebo for 2 weeks , followed by a 13-week period in which no drugs were given . This sequence was repeated 10 times , for a total of 150 weeks . Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups . Vertebral bone mineral content was measured by dual-photon absorptiometry ; spinal radiographs were assessed to identify new vertebral fractures . Vertebral bone mineral content increased significantly ( P less than 0.01 ) after 150 weeks of etidronate therapy ( 5.3 percent ; 95 percent confidence interval , 2.0 to 8.6 ; n = 20 ) but decreased with placebo ( -2.7 percent ; 95 percent confidence interval , -7.3 to 1.9 ; n = 20 ) . The difference between groups was 8.0 percentage points ( P less than 0.01 ; 95 percent confidence interval , 2.4 to 13.6 ) . The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups ( 6 vs. 54 fractures per 100 patient-years ; P = 0.023 ) . No adverse clinical , biochemical , or bone histomorphometric effects of treatment were observed . We conclude that at the end of nearly three years , etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and , after approximately one year of treatment , a significant decrease in the rate of new vertebral fractures BACKGROUND Osteoporosis-related fractures are a considerable economic burden on the U.S. health care system . Since 2008 , the Centers for Medicare Medicaid Services have adopted a Medicare Part C Five-Star Quality Rating measure to ensure that a woman 's previously unaddressed osteoporosis is managed appropriately after a fracture . Despite the effort to improve this gap in care , the 2013 CMS plan ratings fact sheet reported an average star rating of 1.4 stars for the osteoporosis measure , the lowest score for any measure across all health plans . OBJECTIVE To evaluate the impact of conducting a pharmacist-led , telephone outreach program to members or their providers to improve osteoporosis management in elderly women after experiencing fractures . METHODS This was a prospect i ve , r and omized study to evaluate the effectiveness of 3 different intervention strategies within a nationwide managed care population . Women aged 66 years and older who experienced a new bone fracture between January 1 , 2012-August 31 , 2012 , were identified through medical cl aims . Women who were treated with an osteoporosis medication or received a bone mineral density ( BMD ) test within a year of their fractures were excluded . Study patients were r and omized into 3 intervention cohorts : ( 1 ) baseline intervention consisting of member educational mailing and provider educational mail or fax notification ; ( 2 ) baseline intervention plus a live outbound intervention call to members by a pharmacist ; and ( 3 ) baseline intervention plus a pharmacist call to members ' providers to recommend starting osteoporosis therapy and /or a bone mineral density ( BMD ) test . An intent-to-treat and per protocol analyses were employed , and appropriate osteoporosis management ( initiation of osteoporosis therapy and /or BMD testing ) 120 days after the baseline intervention and 180 days after a fracture were measured . RESULTS The study identified 6,591 members who were equally r and omized into 3 cohorts . The baseline demographics in each cohort were similar . Results of the intent-to-treat analysis showed more members in cohort 3 receiving appropriate osteoporosis management ( 13.0 % ) compared with those in cohort 2 ( 10.3 % , P less than 0.005 ) or compared with those in cohort 1 ( 9.1 % , P less than 0.001 ) . No difference was detected between those receiving additional member calls ( cohort 2 ) and those receiving only the baseline intervention ( cohort 1 ) . Similar results were observed utilizing the 180 days after fracture time frame . CONCLUSIONS The effectiveness of a pharmacist-led telephone intervention directed at providers or members was examined in this r and omized study . Pharmacist calls to members did not improve osteoporosis management over member and provider mail and fax notifications . Greater impact was demonstrated by performing a pharmacist call intervention with providers rather than with members Abstract Introduction : Medical intervention plays a key role in the treatment of postmenopausal osteoporosis and patients ’ adherence to therapy is essential for optimal clinical outcomes . While adherence in RCTs is usually around 70–90 % , a previous study showed that in clinical practice only 27.8 % and 46.5 % of the women on oral daily vs. weekly alendronate were still on treatment after 12 months . Data on adherence to teriparatide ( TPTD ) treatment of severe postmenopausal osteoporosis are available from only few countries . This study assessed adherence and persistence with TPTD in Germany . Material and methods : A sample of 50 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the German osteoporosis guidelines was included . Treatment was initiated 12–24 months before recruitment . Patient self report was assessed using a vali date d question naire . In addition medication possession ratio ( MPR ) was calculated by counting prescription refills , and therefore all physicians who were treating the patients for any disease were contacted . Patients were classified adherent at 12 months of therapy if self-reported adherence and an MPR of ≥80 % were achieved . Persistence was calculated in months and analysed with a Kaplan – Meier estimate . Results : Apart from a significantly lower age at menopause in the adherent group ( 46.1 vs. 50.0 ; p < 0.006 ) there were no significant differences in baseline demographics between adherent and non-adherent patients . After 12 months , 80 % of the patients treated with TPTD were adherent , while 20 % were non-adherent . A significant correlation with treatment adherence was found for self-reported medication tolerability ( p < 0.001 ) . Furthermore 79 % of patients were persistent after 12 months . Conclusion : These results indicate that more patients seem to be adherent and persistent with TPTD than with oral treatments of postmenopausal osteoporosis . As these patients suffered from severe osteoporosis and sustained several fragility fractures , the generalisability of our retrospective study analysing a small sample is limited . The major factor that reduced adherence and persistence was tolerability . These findings are of practical relevance as numerous studies on antiresorptive therapies have shown that high adherence and persistence were needed to ensure an optimal therapeutic outcome Elderly postmenopausal women who have osteoporosis sometimes experience low back pain , however , the relationship between low back pain and osteoporosis in the absence of vertebral fractures remains unclear . We examined the relationship between bone mineral density ( BMD ) , bone resorption and low back pain in elderly female patients who did not have osteoporotic vertebral fractures . The average BMD was 0.675 g/cm(2 ) when assessed by dual-energy X-ray absorptiometry ( DEXA ) . Patients were excluded from the study if they had vertebral fractures revealed by radiography , CT scans or MRI . Bisphosphonate ( risedronate ) was administered for 4 months . The visual analogue scale ( VAS ) pain score , Rol and Morris Disability Question naire ( RDQ ) , Short Form-36 ( SF-36 ) question naire , BMD and N-terminal telopeptide of type I collagen ( NTx ; a marker for bone resorption ) were examined before and after treatment .  DEXA did not increase significantly , but serum and urinary NTx were decreased ( -51.4 % and -62.0 % , respectively ) after 4 months of risedronate treatment ( p<0.01 ) . The assessment was repeated using the VAS score , RDQ and SF-36 , which revealed an improvement after risedronate treatment ( p<0.01 ) . A decrease in serum and urinary NTx was associated with improvement of low back pain , suggesting that despite the absence of vertebral fractures , bone resorption due to osteoporosis may cause low back pain Abstract Denosumab is a fully human monoclonal antibody with high affinity and specificity for human receptor activator of nuclear factor kappa B lig and ( RANKL ) , the principal regulator of osteoclastic bone resorption . By binding to RANKL , denosumab prevents it from binding to its receptor on the cell surface of pre-osteoclasts and mature osteoclasts , thereby reducing the formation , activity , and survival of osteoclasts and inhibiting osteoclastic bone resorption . In a large , r and omized , placebo-controlled clinical trial in postmenopausal women with osteoporosis , denosumab 60 mg administered subcutaneously every 6 months reduced levels of bone turnover markers , increased bone mineral density , and reduced the risk of vertebral fractures , hip fractures , and non-vertebral fractures . There was no significant difference between denosumab and placebo in the overall risk of adverse events or serious adverse events .  Denosumab was associated with a significant increase in the risk of eczema and cellulitis , and a significant decrease in the risk of falling and concussions .  Denosumab recently received regulatory approval for the treatment of postmenopausal women with osteoporosis at high risk for fracture , with no dose adjustment in patients with renal impairment .  Denosumab is a new therapeutic option to reduce fracture risk in women with postmenopausal osteoporosis , especially for those with impaired renal function or with intolerance or poor response to oral therapy UNLABELLED It is unclear whether the antifracture efficacy of bisphosphonates depends on pretreatment bone turnover . We analyzed the risedronate phase III clinical programs using the urinary excretion of deoxypyridinoline ( uDPD ) as an index of pretreatment bone resorption rates . Risedronate reduced incident vertebral fractures in women with postmenopausal osteoporosis independent from pretreatment bone resorption . INTRODUCTION Earlier studies on postmenopausal osteoporosis have suggested that the therapeutic efficacy of antiresorptive therapies might be influenced by pretreatment bone turnover . Because all of these studies have used bone mineral density ( BMD ) as the primary endpoint , it remains unclear whether this association holds true for incident fractures . MATERIAL S AND METHODS This study aims to answer this question in a post hoc analysis of a subset of the risedronate phase III clinical programs , using the urinary excretion of deoxypyridinoline ( uDPD ) as an index of pretreatment bone resorption ( PBR ) . A total of 1593 women with postmenopausal osteoporosis that had baseline uDPD values and paired spinal radiographs available were pooled , in similar proportions , from the risedronate multinational and North American VERT , and from the risedronate HIP trials . Patients from treatment and placebo groups were stratified by the uDPD premenopausal normative median . The four result ing groups were balanced for age , years since menopause , body mass index , baseline femoral neck BMD , and number of prevalent fractures , but baseline lumbar spine BMD was significantly higher in patients with low PBR rates . RESULTS In all groups , the proportion of patients with new vertebral fractures was higher in patients with baseline uDPD levels above the normative median . The incidence of vertebral fracture was significantly lower in groups assigned to risedronate compared with placebo . This effect was independent of PBR : in patients with high PBR , the relative risk ( RR ) of vertebral fracture after 1 year of risedronate was 0.28 ( p = 0.03 compared with controls , absolute risk reduction 7.1 % ) . In patients with low PBR , the RR of fracture after 1 year was 0.33 ( p < 0.001 , absolute risk reduction 4 % ) . After 3 years , the RR of fracture was 0.52 ( p = 0.042 , absolute risk reduction 8.3 % ) in patients with high PBR , and 0.54 ( p = 0.002 , absolute risk reduction 7.1 % ) in patients with low PBR . Results were similar after adjusting for age , baseline lumbar spine BMD , and prevalent fractures . The number needed to treat to avoid one vertebral fracture at 12 months was 15 in the group of patients with high PBR and 25 in patients with low PBR . Risedronate significantly increased lumbar spine BMD . During the first year of treatment , women with high PBR gained lumbar spine BMD at a faster rate than patients with low PBR . Treatment-by-PBR status interactions were not significantly different over time . CONCLUSION The efficacy of risedronate to reduce incident vertebral fractures in women with postmenopausal osteoporosis is largely independent of pretreatment bone resorption rates Patients who are diagnosed with osteoporosis and beginning treatment often discontinue their osteoporosis medication relatively early after the start of treatment because of their poor recognition of fracture risk and the asymptomatic nature of osteoporosis . In this study we aim ed to assess adherence to treatment with 1 μg alfacalcidol ( D ) , 60 mg raloxifene ( R ) or a combination of both ( D + R ) for 1 year in postmenopausal Japanese women with osteoporosis or osteopenia . We defined persistence of D and R as continuing to take tablets for more than 7 of any 14 days immediately before the 1-year visit . A total of 137 subjects aged 49–81 years [ 64.9 ± 7.0 years , 16.0 ± 12.7 years since menopause ( YSM ) ] were r and omly assigned to each treatment group . The proportions persisting with each treatment group at 1 year were 61.4 , 65.3 , 55.1 % for D , R and D + R groups , respectively whereas the compliance to each therapy as judged by the medical possession ratio ( MPR ) at 1 year were 77.5 , 93.8 , 78.4 % , respectively . There were no significant differences in persistence , compliance and the number of subjects who discontinued treatment due to adverse events among each group . We found significant inverse correlations in percent changes at 1 year between compliance and serum BAP in R and D + R groups or urinary ( u- ) CTX in the R group . The changes in the level of serum BAP and u-CTX were significantly higher in high-compliance patients ( MPR > 80 % ) treated with raloxifene alone or concomitantly with alfacalcidol compared to those in low-compliance patients BACKGROUND To determine the effects of etidronate ( a bisphosphonate that inhibits osteoclast-mediated bone resorption ) in the treatment of postmenopausal osteoporosis , we conducted a prospect i ve , two-year , double-blind , placebo-controlled , multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia . METHODS The patients were r and omly assigned to treatment with phosphate ( 1.0 g ) or placebo twice daily on days 1 through 3 , etidronate ( 400 mg ) or placebo daily on days 4 through 17 , and supplemental calcium ( 500 mg ) daily on days 18 through 91 ( group 1 , placebo and placebo ; group 2 , phosphate and placebo ; group 3 , placebo and etidronate ; and group 4 , phosphate and etidronate ) . The treatment cycles were repeated eight times . The bone density of the spine was measured by dual-photon absorptiometry , and the rates of new vertebral fractures were determined from sequential radiographs . RESULTS After two years , the patients receiving etidronate ( groups 3 and 4 ) had significant increases in their mean ( + /- SE ) spinal bone density ( 4.2 + /- 0.8 percent and 5.2 + /- 0.7 percent , respectively ; P less than 0.017 ) . The rate of new vertebral fractures was reduced by half in the etidronate-treated patients ( groups 3 and 4 combined ) as compared with the patients who did not receive etidronate ( groups 1 and 2 combined ) ( 29.5 vs. 62.9 fractures per 1000 patient-years ; P = 0.043 ) ; the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line , in whom fracture rates were reduced by two thirds ( 42.3 vs. 132.7 fractures per 1000 patient-years ; P = 0.004 ) . The addition of phosphate provided no apparent benefit . There were no significant adverse effects of treatment . CONCLUSIONS Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis BACKGROUND Nonadherence to treatment is an important determinant of long-term outcomes in women with osteoporosis . OBJECTIVES This study was conducted to investigate the association between adherence and osteoporotic fracture risk and to identify optimal thresholds for good compliance and persistence . A secondary objective was to perform a preliminary evaluation of the cost consequences of adherence . METHOD This was a retrospective case-control analysis . Data were derived from the Thales prescription data base , which contains information on > 1.6 million patients in the primary health care setting in France . Cases were women aged > or=50 years who had an osteoporosis-related fracture in 2006 . For each case , 5 matched controls were r and omly selected . Both compliance and persistence aspects of treatment adherence were examined . Compliance was estimated based on the medication possession ratio ( MPR ) . Persistence was calculated as the time from the initial filling of a prescription for osteoporosis medication until its discontinuation . RESULTS The mean ( SD ) MPR was lower in cases compared with controls ( 58.8 % [ 34.7 % ] vs 72.1 % [ 28.8 % ] , respectively ; P < 0.001 ) . Cases were more likely than controls to discontinue osteoporosis treatment ( 50.0 % vs 25.3 % ; P < 0.001 ) , yielding a significantly lower proportion of patients who were still persistent at 1 year ( 34.1 % vs 40.9 % ; P < 0.001 ) . MPR was the best predictor of fracture risk , with an area under the receiver-operating-characteristic curve that was higher than that for persistence ( 0.59 vs 0.55 ) . The optimal MPR threshold for predicting fracture risk was > or=68.0 % . Compared with less-compliant women , women who achieved this threshold had a 51 % reduction in fracture risk . The difference in annual drug expenditure between women achieving this threshold and those who did not was approximately euro300 . The optimal threshold for persistence with therapy was at least 6 months . Attaining this threshold was associated with a 28 % reduction in fracture risk compared with less-persistent women . CONCLUSIONS In this study , better treatment adherence was associated with a greater reduction in fracture risk . Compliance appeared to predict fracture risk better than did persistence OBJECTIVES To investigate the therapeutic effect of combined use of vitamin K(2 ) and D(3 ) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis . SUBJECTS AND METHODS We enrolled 172 women with vertebral bone mineral density < 0.98 g/cm(2 ) ( osteopenia and osteoporosis ) as measured by dual-energy X-ray absorptiometry . In this study , we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996 . Subjects were r and omized into four groups ( each having 43 subjects in vitamin K(2 ) therapy group , vitamin D(3 ) therapy group , vitamin K(2 ) and D(3 ) combined therapy group , or a control group receiving dietary therapy alone ) and treated with respective agents for 2 years , with bone mineral density was measured prior to therapy and after 6 , 12 , 18 , and 24 months of treatment . The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide ( P1CP ) , serum intact osteocalcin , and urinary pyridinoline . Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time ( APTT ) and analysis of concentrations of antithrombin III ( AT III ) , fibrinogen , and plasminogen . RESULTS Combined therapy with vitamin K(2 ) and D(3 ) for 24 months markedly increased bone mineral density ( 4.92 + /- 7.89 % ) , while vitamin K(2 ) alone increased it only 0.135 + /- 5.44 % . The bone markers measured , revealed stimulation of both bone formation and resorption activity . We observed an increase in coagulation and fibrinolytic activity that was within the normal range , suggesting that balance was maintained in the fibrinolysis-coagulation system . CONCLUSIONS Continuous combination therapy with vitamin K(2 ) and D(3 ) may be useful for increasing vertebral bone mass in postmenopausal women . Furthermore , the increase in coagulation function observed during this therapy was within the physiological range , and no adverse reactions were observed
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 .