ORIGINAL ARTICLE

Adherence to osteoporosis medicationsamongst Singaporean patients

M. H. H. Cheen & M. C. Kong & R. F. Zhang &

F. M. H. Tee & M. Chandran

Received: 31 January 2011 /Accepted: 30 March 2011 /Published online: 19 April 2011# International Osteoporosis Foundation and National Osteoporosis Foundation 2011

AbstractSummary Compliance and persistence to bisphosphonatesamongst Singaporean patients with osteoporosis wereestimated. Mean medication possession ratio (MPR) ±standard deviation (SD) was 78.9±27.5%, and 69.0% waspersistent at 1 year. In contrast to US and Europe wherepoor adherence is noted, our study suggests higheradherence rates to bisphosphonate therapy amongstpatients.Introduction Adherence to bisphosphonate therapy duringtreatment of osteoporosis has been reported to be poor. Weaimed to estimate the compliance and persistence toprescribed bisphosphonate therapy amongst patients at thelargest public restructured hospital in Singapore.Methods This is a retrospective analysis of records ofpatients who were prescribed the two most commonly usedoral bisphosphonates—alendronate and risedronate. Thestudy was conducted between January 2007 and December2008. Prescription and pharmacy refill records of allpatients were extracted and matched. Compliance wascalculated using the MPR, while persistence, a dichoto-mous variable, was defined as continuous refill of

bisphosphonates for at least 12 months with a permissiblegap of 30 days.Results Seven hundred ninety-eight patients were includedin the study. Mean MPR ± SD was 78.9±27.5%, and 69.0%of the patients were persistent with bisphosphonate therapyat 1 year. The proportion of patients with MPR ≥80% at 6,12 and 18 months was 90%, 72% and 62%, respectively.Age <69 years was associated with better compliance (OR,1.34; 95% CI, 0.99–1.82; P=0.043), and history offractures was associated with better compliance (OR,1.38; 95% CI, 1.02–1.87; P=0.038) and persistence (OR,1.33; 95% CI, 0.97–1.82; P=0.046).Conclusion In contrast to studies conducted in the US andEurope that show poor adherence, our study suggestshigher adherence rates to bisphosphonate therapy amongstSingaporean patients.

Keywords Adherence . Bisphosphonate . Compliance .

Osteoporosis . Persistence

Introduction

Osteoporosis is becoming an increasingly important prob-lem in Singapore as it is in the rest of Asia [1–3]. Age-adjusted rates of osteoporotic fractures among women overthe age of 50 years in Singapore are currently among thehighest in Asia and approaching those of the US andEurope [1]. The mortality rate 1 year post fragility hipfracture is approximately 20–27%. Of those who survive,20% become semi- or fully dependent on others foractivities of daily living and 39% experience reducedmobility status [4, 5]. This represents a significant cost to

M. H. H. Cheen :M. C. Kong : F. M. H. TeeDepartment of Pharmacy, Singapore General Hospital,Singapore, Singapore

R. F. Zhang :M. Chandran (*)Osteoporosis and Bone Metabolism Unit,Department of Endocrinology, Singapore General Hospital,1 Hospital Drive,169608 Singapore, Singaporee-mail: manju.chandran@sgh.com.sg

Osteoporos Int (2012) 23:1053–1060DOI 10.1007/s00198-011-1635-9

individuals and society [6] and highlights the importance ofgood osteoporosis management.

The main aim of the treatment of osteoporosis is theprevention of fractures. For the benefit to manifest, patientsmay have to remain on therapy for extended periods.However, a major challenge for any treatment in osteopo-rosis as it is in other chronic and relatively asymptomaticdiseases is the lack of long-term adherence to therapy [7,8]. A retrospective study on adherence to osteoporosismedication found that 45% of patients had discontinuedosteoporosis treatment just 1 year after treatment initiation[9]. Another recent observational study recorded 12-monthadherence rates of 53.8% for daily bisphosphonates and62.5% for weekly bisphosphonates [10]. Conflicting reportsexist on whether a daily or weekly formulation ofbisphosphonate is associated with better adherence, withone report showing improved adherence with weeklyregimens [11] and another showing no difference inadherence between the two [12]. These studies showingpoor adherence have so far been conducted on Caucasianpopulations. As the healthcare system, as well as thepopulation, and the cultural practices in Singapore differfrom that of Western countries, adherence rates tobisphosphonate therapy reported in the West cannot begeneralized to our population. A small study conducted in1997 examining primary non-compliance rates amongstSingaporeans suggested that non-compliance rate amongpatients with chronic illnesses like diabetes may bemarkedly lower in the local population when compared tothat in the UK [13].

Although numerous studies in the US and Europe haveused medical claims data or pharmacy refill records toestimate compliance and persistence rates to bisphosphonatetherapy [11, 14–19], no such study has previously beenconducted in Singapore. An observational study comparingraloxifene and bisphosphonates based on adherence andtreatment satisfaction in postmenopausal Asian womenconcluded that osteoporotic women taking raloxifeneexhibited lower discontinuation rates and higher treatmentsatisfaction compared to bisphosphonates [20]. However,this study had several limitations, including the fact that thedata were collected through a questionnaire administered topatients. It thus relied on the ability of the patients to reportaccurate information and it was not obtained from adminis-trative data sets.

The aim of this study was to estimate the complianceand persistence of patients prescribed oral bisphosphonatesthrough a retrospective examination of the pharmacyprescription refill records of the largest public restructuredhospital in Singapore. This study is the first of its kind notonly in Singapore but also, to the best of our knowledge, inthe rest of Asia. Thus, it will be of immense importance asit addresses a neglected but very important aspect of

chronic disease management—adherence to a prescribedtreatment regimen.

Methodology

Definition of medication adherence

According to the definitions issued by the International Societyfor Pharmacoeconomic and Outcomes Research, adherence isa general term encompassing both compliance and persistence[21]. Compliance is defined as the extent to which a patientacts in accordance with the prescribed interval and dose of adosing regimen. It is typically expressed as the number ofdoses taken divided by the number of doses prescribed, oftenknown as medication possession ratio (MPR). Persistence, onthe other hand, is defined as the duration of time frominitiation to discontinuation of therapy. It can be expressed asa continuous variable in terms of number of days for whichtherapy was available or as a dichotomous variable measuredat the end of a predefined time period (e.g. 12 months) [22].Non-persistence is assumed to be the same as discontinuationif a prescription refill gap is longer than a set number of daysknown as the permissible gap (PG).

Study design and population

This study was a retrospective analysis of patients whowere prescribed either of the two most commonly used oralbisphosphonates in Singapore—alendronate (Fosamax®)and risedronate (Actonel®). This study was conducted atthe Singapore General Hospital—the country’s largestpublic restructured hospital. The index study period wasbetween January 2007 and December 2008. A total of5,188 patients were prescribed either alendronate orrisedronate during this period. From this population, 1,500patients were randomly selected using a computerizedrandom number generator. The prescription records of allthese patients were extracted from the patient recordsmanagement system (CITRIX®), while the pharmacy refillrecords were extracted from the pharmacy patient purchaserecord system (MAXCARE®). The data from these twosystems were matched patient for patient. Patients whowere prescribed oral bisphosphonates during the studyperiod and had at least 12 months of prescription datacaptured in CITRIX® were included in the study. It is acommon practice in Singapore for doctors to manually add inrepeat refills for the same prescription on the prescriptionprintout. This additional information is not captured inCITRIX®, which can result in over-estimation of the MPR.Furthermore, too short a duration of prescription data wouldbe inadequate to assess MPR. In order to overcome this, onlypatients who had <12 months of prescription data captured in

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CITRIX®were excluded. Our approach is also similar to otherstudies that have employed a methodology in which patientswere required to have 12months of continuous enrolment data[23]. Patients without pharmacy refill records were alsoexcluded. Patients who switched regimen during the studyperiod were analysed separately and their compliance andpersistence before and after switching were calculated. Usinga pre-estimated compliance of 50% based on previousstudies [24–26], with a confidence level of 95% and amargin of error of 4.5%, a sample size of 550 was required.

Seven hundred ninety-eight patients met the inclusioncriteria. Of the 702 patients excluded from the study, 179patients did not have pharmacy refill records and 523 had<12 months of prescription records. Patient data capturedduring extraction included age, gender, ethnic group, doseand regimen of oral bisphosphonate prescribed, durationprescribed and duration of pharmacy refills. Fracturehistory in the past 15 years was obtained from the patients’medical records. Approval for the study was obtained fromthe Centralized Institutional Review Board of our institu-tion and the study conforms to the provisions of the WorldMedical Association Declaration of Helsinki.

Outcome measures

The outcome measures of this study were compliance,determined by MPR, and persistence. Although compar-isons have been made previously among methods ofcollecting data to assess adherence, no gold standardmeasure has been established [21, 27, 28]. Therefore, it isimportant to specify the measure used to calculate medica-tion adherence. The following methods were used tocalculate compliance and persistence in our study:

Compliance: MPR ¼ Duration of pharmacy refillsDuration of bisphosphonates prescribed � 100%

Persistence: Expressed as a dichotomous variable (persis-tent or not). As required for persistence analysis, a limit onthe number of days allowed between refills, the PG, waspre-specified. In this study, a patient was persistent withtherapy if there were continuous refills of bisphosphonatesfor at least 12months. Patients who stopped their treatmentfor a duration longer than the PG were considered to havediscontinued, even if they subsequently resumed treat-ment. A pre-specified PG of 30 days was used in this studybased on previous studies done [17, 29–31].

Statistical analyses

Descriptive statistics were used to summarize patientdemographics (age, gender and ethnicity), fracture history,type of bisphosphonate prescribed, compliance, persistence

and total duration of pharmacy refills. Patients with MPR≥80% were categorized as compliant based on previousstudies [14, 30, 32], while patients with MPR <80% werecategorized as having lower compliance [24].

As the Kolmogorov–Smirnov test showed that MPR wasnot normally distributed, non-parametric statistical testswere used. Comparison of the mean MPR between patientsaged ≥69 years and those aged <69 years was made usingMann–Whitney U test. The decision to use 69 years as theage cutoff between the two groups was based on twoprevious studies that have shown a significantly higher riskof hip fractures in patients ≥69 years old due to poorercompliance [11, 33]. Mann–Whitney U test was also usedto compare the mean MPR between patients prescribedalendronate and those prescribed risedronate. The samecomparisons were performed for persistence but Pearson’schi-square test was used instead as persistence is an ordinaldata. In addition, the patients were subdivided into thosewith MPR ≥80% and MPR <80%, and Pearson’s chi-squaretest was used to identify any statistical significance betweenthe degree of compliance and age, as well as whether therewas a history of fracture or not and the type ofbisphosphonate prescribed. The median duration of phar-macy refills was compared between patients aged ≥69 yearsand those aged <69 years, as well as between patients withhistory of fractures and those without. Sensitivity analysesusing varying PGs (45, 60 and 90 days) and MPRthresholds (50% and 90%) were performed.

Kaplan–Meier survival plots were used to analyse thetime to become non-compliant (MPR <80%) and the timeto discontinuation of treatment. Kruskal–Wallis one-wayanalysis of variance (ANOVA) was performed to comparemean compliance between age groups, and post hocanalysis was performed if ANOVA showed statisticalsignificant difference between age groups. Fisher’s exacttest was used to compare persistence between age groups.Multivariate analysis using stepwise logistic regression wasused to identify independent determinants of good compli-ance (MPR ≥80%) and persistence, with variables with aP value of <0.2 from univariate analyses included in themodel.

The analysis was performed using IBM® SPSS Statistics19.0 and results were considered to be statisticallysignificant if the corresponding P value was below 0.05.

Results

Study sample and demographics

Mean age was 68.5±10.8 years, with 50.6% of the patientsaged ≥69 years. Patients were predominantly female(92.0% female, 8.0% male), and most were Chinese

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(91.6% Chinese, 1.9% Malay, 3.8% Indian and 2.8%others). Relatively equal number of patients did or did nothave a history of previous fracture (47.1% history offracture and 52.9% no fracture history). Fourteen (1.8%)patients were on daily therapy and 784 (98.2%) were ononce weekly regimen. The mean duration of pharmacyrefills was 14.3±6.4 months. Mean MPR ± standarddeviation (SD) at 2 years was 78.9±27.5%, and 69.0% ofthe patients were persistent with bisphosphonate treatmentat 1 year. Of the patients, 64.0% were found to have anMPR ≥80%. Patient demographics are presented in Table 1.

Compliance (MPR)

The mean MPR for the 24-month study period did not showsignificant difference between patients aged ≥69 years andthose aged <69 years (77.4±28.2% for age ≥69 years, 80.5±26.7% for age <69 years; P=0.060). There was nosignificant difference in mean MPR between alendronateand risedronate (79.3±27.6% for alendronate, 78.3±27.3%for risedronate; P=0.670). No significant difference inmean MPR was found between patients with or withouthistory of fractures (80.6±26.2% for past fractures, 77.4±28.5% for no past fractures; P=0.083).

The 80% threshold of good compliance was achieved bya similar percentage of patients aged ≥69 years and those

aged <69 years (61.6% for age ≥69 years, 66.5% for age<69 years; P=0.152). No significant differences betweenpercentages of patients attaining an MPR of 80% werefound between alendronate and risedronate (66.0% foralendronate, 60.8% for risedronate; P=0.138), as well aspatients with or without history of fractures (67.3% for pastfractures, 61.1% for no past fractures; P=0.071). Sensitivityanalysis showed that the proportion of patients achievingMPR thresholds of ≥50% and ≥90% was 83.3% and 53.5%,respectively. Multivariate analysis identified age <69 years(OR, 1.34; 95% CI, 0.99–1.82; P=0.043) and history offractures (OR, 1.38; 95% CI, 1.02–1.87; P=0.038) asindependent determinants of good compliance (MPR≥80%; Table 2).

Kruskal–Wallis one-way ANOVA of the mean MPRbetween age groups showed statistical significance (P=0.002), and post hoc analysis showed significant differencein mean MPR between the following age groups: 60–69 and80–89 years (P=0.012); 60–69 and >89 years (P=0.027;Table 3). Kaplan–Meier survival analysis showed that theproportion of patients maintaining good compliance (MPR≥80%) at 6, 12 and 18 months was 90%, 72% and 62%,respectively (Fig. 1).

Persistence

Persistence was not significantly different between patientsaged ≥69 years and those aged <69 years (68.3% for age≥69 years, 69.8% for age <69 years; P=0.651), as well asthe type of bisphosphonate prescribed (70.8% for alendro-nate, 66.1% for risedronate; P=0.163) and whether or notthe patients had a history of fracture (72.1% for pastfractures, 66.4% for no past fractures; P=0.081). When thePG was increased to 45 days, persistence increased to73.0%, which subsequently increased to 75.1% when thePG was increased to 60 days. Persistence was at 78.1%when the PG was increased to 90 days. Multivariateanalysis identified history of fractures as an independentdeterminant of persistence (OR, 1.33; 95% CI, 0.97–1.82;P=0.046; Table 3). Fisher’s exact test showed significantdifference between persistence and age (P=0.024; Table 3).Kaplan–Meier survival analysis showed that 75%, 50% and

Table 1 Demographic data of patients included in the study (n=798)

Characteristics

Mean age ± SD, years 68.5±10.8

Gender, % (n)

Female 92.0 (734)

Ethnicity, % (n)

Chinese 91.6 (731)

Malay 1.9 (15)

Indian 3.8 (30)

Others 2.8 (22)

Fracture history, % (n)

Yes 47.1 (376)

No 52.1 (422)

Bisphosphonate, % (n)

Alendronate 62.3 (497)

Risedronate 37.7 (301)

Regimen

Daily, % (n) 1.8 (14)

Weekly, % (n) 98.2 (784)

Mean MPR ± SD, % 78.9±27.5

Mean duration of pharmacy refills ± SD, months 14.3±6.4

Persistent, % (n) 69.0 (551)

MPR ≥80%, % (n) 64.0 (511)

Table 2 Independent determinants of compliance and persistence

OR (95% CI) P value

Good compliance (MPR ≥80%)

Age <69 years 1.34 (0.99–1.82) 0.043

History of fractures 1.38 (1.02–1.87) 0.038

Persistence

History of fractures 1.33 (0.97–1.82) 0.046

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30% of patients were still refilling their prescriptions at 15,18 and 21 months, respectively (median duration,17 months; Fig. 2).

Daily versus weekly bisphosphonates

Seven patients switched from daily to weekly bisphospho-nate therapy during the study period. The mean MPRbefore and after the switch were 76.5% and 88.9%,respectively. Fourteen patients remained on dailybisphosphonate therapy throughout the study period. Whenanalysed separately, patients on weekly bisphosphonatetherapy had a higher MPR (daily, 67.7%; weekly, 79.1%)and were more persistent (daily, 42.9%; weekly, 69.5%)compared to the patients on daily bisphosphonate therapy.However, these results should be evaluated with caution asthe number of patients was small and no statisticalcomparisons could be made.

Discussion

Singapore’s healthcare system has developed tremen-dously over the years, and the efforts put in by theMinistry of Health has earned the country manyaccolades, including being ranked sixth out of 191countries on overall health system performance by theWorld Health Organization [34]. Singapore’s healthcarefinancing system is anchored on the twin philosophies ofindividual responsibility and affordable healthcare to all.Through this mixed financing system, Singapore is able tomaintain the national healthcare expenditure below 4% ofthe gross daily product [35]. A medication co-paymentexists in which medications are subsidized by thegovernment based on the financial class of the patient,but the patient has to bear the remaining cost of themedications. With this medication co-payment system,patients are more likely to be responsible for themedications that they have paid for and be adherent tothe treatment regimen. This could be a contributing factorto the much higher mean MPR and persistence at24 months compared to studies done in the US andEurope [14, 26, 36].

Fig. 2 Kaplan–Meier survival analysis of time to discontinuation ofbisphosphonate therapy

Fig. 1 Kaplan–Meier survival analysis of compliance to bisphosph-onate therapy

Age group (years) n (%) Mean MPR (%) P value Persistence (%) P value

<40 8 (1.0) 74.2 0.002a 63.0 0.02440–49 21 (2.6) 72.1 67.0

50–59 131 (16.4) 77.5 63.0

60–69 260 (32.6) 83.5 74.0

70–79 243 (30.5) 79.4 73.0

80–89 123 (15.4) 73.4 61.0

>89 12 (1.5) 58.1 42.0

Table 3 Compliance and per-sistence by age groups

a Post hoc analysis found signifi-cant differences in the mean MPRbetween the following age groups:60–69 and 80–89 years (P=0.012); 60–69 and >89 years(P=0.027)

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Our study suggests that Singaporeans are likely to remainadherent to bisphosphonate therapy for at least 12 monthsafter initiation, compared to reports from elsewhere that showa dropout rate of 50–75% after 12 months [19, 36–38].Sensitivity analysis of persistence showed that approximatelyone third of patients who discontinued therapy restartedwithin 3 months. This result is consistent with a studyconducted to determine the persistence of weekly alendro-nate amongst osteoporotic women [39]. Although univariatestatistical analyses failed to show any causative patientfactors that could have resulted in the higher adherence, theremay be other non-measurable factors which could haveresulted in this better adherence to bisphosphonate therapy.These could include the Asian cultural background, wherebypatients may tend to be more compliant and adherent to theadvice of physicians and other healthcare professionals. Thesystem of individual responsibility and co-payment ofmedications could also be the main driving force behindbetter adherence. These reasons need to be validated andelucidated through further studies.

A study conducted in 1997 in a Singapore polyclinicevaluated the rate of primary non-compliance in 500prescriptions issued consecutively [13]. The results showedthat the primary non-compliance rate was 4.0% of theprescriptions issued, with a majority of non-compliantpatients having an acute complaint. Only one patient onchronic follow-up was non-compliant. The investigators ofthe study compared their findings to those of studiesconducted in the UK and Australia and concluded that theprimary non-compliance rate of chronic patients inSingapore is in fact much lower. Our findings are consistentwith that of this study, in that the adherence rates amongstSingaporeans to therapy for a chronic disease such asosteoporosis appear to be higher than those reported inWestern countries.

Studies using medication claims databases have shown acorrelation between fractures and poor adherence withantiresorptive agents. One study showed that women whowere compliant (MPR ≥80%) for the 24-month studyperiod had a 16% lower fracture rate than non-compliantwomen [24]. The other study, which involved a largercohort of patients, showed that non-compliance (MPR<80%) resulted in a 17% increase in fracture rates duringthe follow-up period of 1.7 years [30]. In another studywhich looked at paid claims data from a large healthinsurance company, persistence significantly reduced therate of hip fractures (OR, 0.382; P<0.01) and vertebralfractures (OR, 0.601; P<0.05) [31]. Although fracture riskreduction was not looked at in our study, the much higheradherence to bisphosphonate therapy that we found in ourpopulation may be associated with a reduced risk offractures, and this will have to be examined in a largeprospective trial.

Our study showed that patients with a history offractures are more likely to be adherent to bisphosphonatetherapy. This result is consistent with a previous study thatshowed a strong association between history of fracturesand adherence [14]. The experience of a past osteoporoticfracture could have been traumatic to both patients andfamily members as it caused them physical, psychologicaland financial inconvenience. This could be a possibleexplanation for an improved adherence to bisphosphonatetherapy as patients and family members regard a recurrentosteoporotic fracture as unacceptable and thus would bemore receptive to physician advice to be adherent to theprescribed treatment regimen. Age was a factor stronglyassociated with adherence in our study, with a significantlylower MPR and persistence in patients beyond the age of80. Multivariate analysis also identified a significantcorrelation between age and MPR. Similar results havealso been demonstrated in other studies, which showed adecline in adherence in patients beyond the age of 80 [14,33]. This is an issue of concern as osteoporosis is primarilya disease of the aged and non-adherence to bisphosphonatetherapy can potentially increase the risk of fractures [14].

Our study does have certain limitations. Pharmacy refillrecords and administrative claims are indirect measures ofmedication-taking behaviour and the presence of a phar-macy refill or prescription claim does not necessarily implythat the medication was effectively ingested [40, 41]. Thisis particularly important for bisphosphonates as patientshave to take the medication before any food to maximiseabsorption and subsequently remain upright for at least30 min to prevent oesophageal irritation. We could notexclude the possibility that the patients had refilled theirprescriptions, but did not take them properly according tothe strict instructions. Nonetheless, using pharmacy refillrecords and administrative claims data are commonly usedmethods to estimate compliance and persistence and theyhave been found to be a reliable estimate of medicationadherence [42].

Some important information was not available in ourdatabase. Demographic data were limited to age, gender,ethnicity and fracture history. Other confounders like co-morbidities, body mass index, smoking and alcohol status thatmay relate to compliance were not available in the database.Ours was a cross-sectional study and included both patientswho had been started on bisphosphonates prior to 2007 as wellas bisphosphonate-naive users and did not have patient-specific end dates. However, our decision to adopt a specifiedtime period for the study, i.e. 2 years, is supported by otherinvestigators who have shown that, when using claimsdatabases in which patient-specific end dates are not available,a time frame should be established a priori so that the valuescan be calculated consistently across the patient population[21]. Another limitation is the fact that only pharmacy refill

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records of patients who refilled their prescriptions at ourhospital were captured in the MAXCARE® system. Wecould not exclude the possibility that patients could haverefilled their prescriptions at other pharmacies. Consequently,patients could be misclassified as non-adherent if they hadrefilled their prescription at other pharmacies, and as a result,underestimating the MPR and persistence of our studypopulation.

However, our study has several strengths. A total of 798patients were included in the study. This exceeded the requiredsample size to achieve a confidence level of 95% and a marginof error of 4.5%. This added robustness to our results and wastherefore more than adequate to elucidate the goal of our study—to assess adherence to bisphosphonate therapy. Althoughthis was a retrospective study, the randomized selection ofpatients to be included in the study eliminated any likelybiases related to the demographics of the population. Anotherstrength of our study is that our study subjects wererepresentative of the general patient population of Singaporesince they included patients from all strata of society and thosewho were seen by a multitude of specialties. The use ofcomputerized records allowed us to capture the pertinent datain its entirety, compared to conducting patient interviews andsurveys, which are associated with biases, missing data andinaccurate accounts by patients.

Conclusion

Our study suggests that, although compliance as estimatedby MPR appears to be better in our population than whathas been reported in the Western population, it is still notadequate. Measures to improve adherence can be several,but no clear trends regarding successful interventiontechniques have been identified in studies so far [43].Intervention strategies that improve communicationbetween the healthcare provider and patient, for example,the setting up of a fracture liaison programme that serves asa bridge between the healthcare provider and the patient,may improve patient awareness and adherence. Thisfracture liaison programme could be implemented with thehelp of trained nurses or coordinators who screen high-riskpatients or identify patients with fragility fractures. Oncethe identified patients are started on appropriate therapy,they can be followed up regularly either through face-to-face or through telephone or electronic mail contact.Pharmacists may also serve a very useful role in thisregard—by providing patient education about the appropri-ate mode of administration and expected side effects. Sincelack of affordability is a likely reason for non-adherencewith anti-osteoporosis medications, measures to bringmedication costs down at manufacturer, hospital or govern-ment level also need to be looked at.

Compliance and persistence are extremely important for avariety of people with interest and investment in osteoporosis.Stakeholders for compliance and persistence include health-care providers, pharmaceutical companies, pharmacists, care-takers and, most importantly, the patients. All of thesestakeholders could play a potential role in improvingcompliance and persistence, but ultimately, the decision tobe adherent to the treatment lies with the patient.

Acknowledgements We would like to thank the SingHealthIntegrated Health Information Systems department for their kindassistance in extracting the prescription records and the pharmacyrefill records.

Conflicts of interest None.

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