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
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
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 .