adherence with medications used to treat osteoporosis: behavioral insights

CURRENT THERAPEUTICS (SL SILVERMAN, SECTION EDITOR)

Adherence with Medications Used to Treat Osteoporosis:Behavioral Insights

John T. Schousboe

Published online: 19 January 2013# Springer Science+Business Media New York 2013

Abstract Non-persistence (never starting or stopping med-ication prematurely) and non-compliance (taking medica-tion inappropriately) with fracture prevention medicationamong those at high risk of fracture remain significantbarriers to optimal reduction of osteoporotic fractures. Cur-rent research suggest that for patients to persist and complywith prescriptions for fracture prevention medication, theyneed to believe that they are at significant risk of fracture,that the prescribed medication can safely reduce their risk offracture without exposing them to long-term harm, thatequally effective non-medicinal therapies are not available,and that they can successfully execute medication use in thecontext of their daily task demands. Further research isneeded to understand; a) the mental models of osteoporosis,fractures, and medications used to treat osteoporosis thatpatients employ when making decisions as to whether ornot to take fracture prevention medication; and b) howpatients arbitrage information from various sources (healthcare providers, family, friends, and other sources) to formu-late their beliefs about osteoporosis and medications used totreat it.

Keywords Medication persistence . Medicationcompliance . Beliefs about medications . Osteoporoticfractures

Introduction

Optimal reduction of fracture risk often requires the use ofmedications for prolonged periods of time. Many individu-als prescribed fracture prevention medication do not filleven the first prescription, stop taking them prematurely,or do not take them at the appropriate times in the correctdosage and manner, thereby limiting their effectiveness [1•].This article will review the medical literature regarding theetiology of non-persistence and non-compliance with frac-ture prevention medications, focusing specifically oninsights regarding medication-use behaviors that have beengleaned from the fields of health psychology, and medicalsociology.

Definition of Terms

Numerous terms with overlapping meanings that describethe phenomenon of not taking medication as recommendedhave appeared in the medical, psychological, and sociolog-ical literature over the years. For the purpose of this chapter,I will adopt the term “adherence” to refer to the collection ofways in which patients’ follow recommended instructionsfor use of medications [2]. Primary non-adherence is de-fined as not filling a prescription from a health care providereven once at a pharmacy. With secondary non-adherence,the medication is filled at least once but is either stoppedaltogether prematurely (called non-persistence) or the med-ication is taken at the wrong time intervals or wrong manner(non-compliance) [3].

Epidemiology of Medication Non-Adherence

Strikingly, the time course of medication non-adherence issimilar across chronic conditions, particularly if the condition

J. T. Schousboe (*)Park Nicollet Osteoporosis Center and Park Nicollet Institutefor Research and Education, Park Nicollet Health Services,3800 Park Nicollet Blvd.,Minneapolis, MN 55416, USAe-mail: [email protected]

J. T. Schousboee-mail: [email protected]

J. T. SchousboeDivision of Health Policy and Management, School of PublicHealth, University of Minnesota, Minneapolis, MN, USA

Curr Osteoporos Rep (2013) 11:21–29DOI 10.1007/s11914-013-0133-8

is asymptomatic in the present time and medication is beingadvised to reduce the risk of adverse health events that mayoccur in the future [1•]. In the United States, 15 % to 22 % ofall prescriptions are never filled [4, 5, 6•], and among firstprescriptions of a new medication, 28 % are never filled [6•].Among the remainder who fill a first prescription, about 30 %do not fill it a second time, and by 1 year about 50 % of thosewho filled the first prescription have become non-persistent[7]. The rate of incident non-persistence then becomes lower,but does accumulate over time such that among those who fillthe first prescription, persistence 2 or 3 years later may be aslow as 30%.Among bisphosphonate users, up to 60% re-startmedication (usually a different medication than the first one)after becoming non-persistent with the first one [8]. Duringperiods where a medication is being refilled recurrently, about50 % to 70 % are compliant (when defined as taking themedication at least 80 % of the time as instructed).

Adherence with weekly oral bisphosphonates is modestlybetter than with daily bisphosphonates [9, 10], but it remainscontroversial as to whether or not adherence with oralmonthly bisphosphonate therapy is better than with weeklytherapy [11, 12]. Although surveys generally show thatpatients would prefer once yearly intravenous therapy overoral bisphosphonate therapy [13], the only study that hasevaluated persistence with IV zoledronic acid in the contextof clinical practice reported that only 36 % of those who hadreceived an initial infusion returned 1 year later and agreedto receive a second infusion [14].

No specific patient characteristics have been consistentlyshown to be associated with non-adherence. Increasing age isassociated with higher persistence in some studies [9], lowerpersistence in others [15], and is unassociated with persistencein yet other studies [16–18]. It is unclear whether or not menare more likely [6•, 19•] or less likely [20] than women to benon-persistent with osteoporosis medication therapies. Al-though data for osteoporosis medication is lacking, low socio-economic status has been associated with both primary non-adherence to prescriptions for oral medication in general [21].

Health care claims for previous fractures are associatedwith better persistence in some studies [15, 22] but notothers [16, 23, 24]. However, having had a bone densitytest [15, 25] and accurate knowledge of the results of thattest [26–29] are associated with persistence to fracture pre-vention medication. Concomitant prescriptions for a protonpump inhibitor or H2 blocker medication are specificallyassociated with lower persistence with oral bisphosphonatemedication, perhaps because these medications are used totreat dyspepsia that may sometimes be attributed tobisphosphonate use [30, 31]. Use of glucocorticoid medica-tion has been associated with lower adherence in 2 studies[16, 23], and was unassociated with adherence in another[24]. Smoking was associated with non-persistence withfracture prevention medications in 1 study [30]. Cognitive

impairment adversely affects adherence to oral medicationsused to treat a variety of chronic illnesses [32–36].

Numerous studies have now established that non-adherenceto fracture prevention medication is associated with increasedfractures [37, 38, 39•]. Rabenda and colleagues noted a linear4 % increase in the incidence of hip for every 10 % decrease incompliance (assessed as percent days covered from pharmacyclaims) [40]. Landfeldt and colleagues in Sweden have showna linear increase in incident clinical fractures requiring hospi-talization with increasing time of persistence with fractureprevention medication [19•]. Costs attributable to fractures(and to some degree to wasted medication) [41] rise substan-tially with medication non-adherence [42, 43].

Whether or not a high level of medication compliance isassociated with other favorable health related behaviors (the“healthy adherer effect”), such as receiving influenza andpneumonia vaccinations, and preventive cancer screeningservices, remains controversial [44]. In the Women’s HealthInitiative study, a higher adherence to study drug in the pla-cebo group was associated with lower incidence rates of hipfractures, myocardial infarction, cancer death, and all-causemortality [45]. In the Fracture Intervention Trial of alendro-nate vs placebo, greater compliance in the placebo group wasassociated with lower rates of total hip bone loss but was notassociated with a lower incidence of clinical fracture [46]. Theextent to which differences in health care costs between thosewith high compared with low levels of adherence to fractureprevention medication can be explained, if at all, by thehealthy adherer effect remains unsettled.

Etiology of Non-Adherence to Fracture PreventionMedication: Proximal Behavioral Factors

Given the pervasive nature and consequences of osteoporo-sis medication non-adherence, understanding the etiology ofthe phenomenon is critical to craft practical managementstrategies that may mitigate the problem. As noted above,standard epidemiologic data has shed little light on thecausation of medication non-adherence.

Several studies have used survey methods to assess self-reported reasons for discontinuing fracture prevention therapy.Side effects is the most commonly reported reason for doingso [47, 48], but drug cost, concerns about possible harm fromthe medication, and lack of motivation to address osteoporosisare also cited as reasons for non-persistence [29, 49].

Several common themes emerge from focus group studiesof patients being treated for osteoporosis, hypertension, epilep-sy, diabetes, and other chronic diseases. Most patients need tobe convinced that they have a health problem that requires asolution, that equally effective non-medicinal remedies are notavailable, and that the proposed medication is safe. Ambiva-lence regarding use of medications is very common. While the

22 Curr Osteoporos Rep (2013) 11:21–29

majority of patients in 1 survey study agreedwith the statement“modern medicines have improved people’s health” [50], sev-eral concerns about medications are common even in theabsence of side effects. Many worry about the risk of harmfrom medications [51–55], sometimes linking such risks toperceptions that medications are artificial substances [51–56].Some describe a sense of loss of control when agreeing to takemedication [55–58], and dislike sensing that that their healthstatus depends on taking medication [52–57, 59]. Taking med-ication can also challenge a person’s social identity in part byforcing them to accept that they do have an illness or healthcondition that requires management with the accompanyingsense of vulnerability, [52–54, 57, 59]. Many patients believethat physicians are too quick to suggest medication as a

solution to a medical problem, and that physicians overusemedications (Table 1) [51, 53–55].

Dowell and Hudson found a range of beliefs about medi-cations in their focus group study that could be categorized into3 groups (Fig. 1) [60]. “Believers” in medications had morefaith in their physicians’ recommendations to take medication,whereas “Skeptics” were more likely to distrust medicationsand embrace non-medicinal remedies. A third group of “activemedication users”more actively considered perceived benefitsand drawbacks to taking medication, and were prone to alteruse of the medication to limit their exposure. Sale and col-leagues have recently reported that about half found the deci-sion as to whether or not to take fracture prevention medicationa difficult one and weighed carefully the perceived risks andbenefits of the medication (similar to the “active medication

Table 1 Qualitative studies of patients’ medication concerns

Study/citation/diagnoses Fear/concern

Direct harma Dependence Loss of socialidentity

Loss of controlover healthmanagement

Artificialityof meds

Lack ofunderstandinghow theywork

Physicianoveruse ormisuse ofmedication

Unson et al. 2003, [51]Osteoporosis

X X X X

Britten 1994, GeneralPractice [52]

X X X X

Conrad 1985, Epilepsy [57] X X X

Adams 1997, Asthma [59] X X

Lin et al. 2003, [53]Depression

X X X X X

Donovan 1992 [56]Rheumatoid Arthritis

X X X X

Benson and Britten 2002[54] Hypertension

X X X X X

Horne [55] 1999 Renalfailure or MI

X X X X X X

a Especially with long-term or continuous use

Evaluate Try

Modify

Skeptics BelieversTesters

Problem

Medication Rejected

Medication Accepted

Medication Use Altered

Fig. 1 Therapeutic decision model regarding medication use. Adaptedfrom: Dowell J, Hudson H. A qualitative study of medication-takingbehavior in primary care. Fam Pract. 1997;14(5):369-75

Perceived Susceptibility to Condition

Perceived Severity of Condition

Disease Threat

Perceived Effectiveness of Medication Perceived

Benefit of Taking Medication

Perceived Barriers to Taking Medication

Medication Persistence & Compliance

Cues to Action

Medication Use Self-Efficacy

Concerns about or Distrust in Medicines

Fig. 2 Modified extended health belief model to explain fractureprevention medication use behavior

Curr Osteoporos Rep (2013) 11:21–29 23

users” in Dowell and Hudson’s study) [61•]. Half of this subsetchose not to start fracture prevention medication.

Several explanatory conceptual frameworks of medica-tion non-adherence have been proposed over the last fewdecades, based on social cognition theories such as theHealth Belief Model [62], the Theory of Planned Behavior[63], the Self-Regulatory Model [64], and the Self-EfficacyModel of Bandura [65]. The Extended Health Belief Modelposits medication adherence as a decision making processwhereby the patient weighs the perceived benefits of under-taking the medication, the perceived barriers to carrying outmedication-use behavior, and whether or not they perceivethey have the ability to successfully take the medication inthe context of their daily lives (medication use self-efficacy)(Fig. 2) [66–68]. Whether or not the problem is of sufficientmagnitude to warrant intervention depends on the perceivedsusceptibility to the condition, and the perceived severity ofthe condition should it occur. Patients also need to haveconfidence that they can successfully take the medicationin the context of their daily lives (medication use self-efficacy), and the skills to actually do so.

Perceived Benefits from Taking Fracture PreventionMedication

Other than the experience of actual side effects, the per-ceived benefit from taking fracture prevention medicationis perhaps the strongest predictor of overall adherence andspecifically persistence with fracture prevention medica-tion. Cline and colleagues evaluated the associations be-tween various medication and osteoporosis beliefs andself-reported use of anti-resorptive agents among 984 com-munity dwelling post-menopausal women [69]. Perceivedbenefits of taking the anti-resorptive drug, as measured bythe Osteoporosis Health Belief Scale, were modestly asso-ciated with self-reported use of an anti-resorptive agent(odds ratio 1.34). McHorney and colleagues assessed com-pliance using pharmacy claims data (defined as percentdays covered) among 1092 women age 45 and older whohad filled at least 1 prescription for a weekly or monthlybisphosphonate [70]. While actual experienced side effectswas most predictive of poor compliance, those in thelowest tertile of drug effectiveness beliefs were far morelikely to be non-compliant that those in the top tertile (oddsratio 5.70).

Yood and colleagues assessed the associations betweenmedication and osteoporosis beliefs and primary adherence(filling the initial prescription at least once) among 236women enrolled in a managed care plan [71]. Those withstrong beliefs in the effectiveness of the fracture preventionmedication have an odds ratio of 2.04 of filling an initialprescription for a fracture prevention medication comparedwith those with weak medication effectiveness beliefs.

Schousboe and colleagues subsumed perceived effective-ness under the concept of perceived necessity of medication[72•, 73•], postulating that perceived necessity would reflectbelief not only in the effectiveness of the medication, butthat better non-medicinal alternatives were not available.Among 686 surveyed patients with at least 1 prescriptionfor bisphosphonate therapy, the odds ratio of self-reportednon-persistence (defined as stopping medication for morethan 1 month) was 0.54 for each standard deviation increasein perceived need for fracture prevention medication [72•].However, perceived need for medication was not associatedwith non-compliance (defined operationally as missing 1 ormore doses over the past month among the subset of surveyrecipients who had an active prescription for a fractureprevention medication at the time of the survey).

Perceived Susceptibility to and Severity of Fractures

Cline and colleagues found perceived self-reported use of anti-resorptive agents to be associated with perceived susceptibilityto fractures, but not to perceived severity of fractures [69]. Incontrast, Schousboe et al. found both perceived susceptibilityto and perceived severity of fractures to be associated withperceived need for fracture prevention medication. Each stan-dard deviation increase of perceived susceptibility to fracturesincreased the perceived need for medication by 0.29 standarddeviations, and each level increase of perceived severity(health effects) of fractures increased perceived need for me-diation by 0.25 standard deviations [73•]. Similarly, usingpharmacy claims data, Solomon et al. reported that disagree-ment with statements that “osteoporosis is a worry” or “abroken bone will cause disability” were associated with oddsratios of 3.3 and 2.5 of having PDC less than 20 % comparedwith a PDC of 20 % or higher [74].

Concerns About or Distrust in Medication

Five of the 6 studies that than have evaluated the association ofmedication and osteoporosis beliefs with fracture preventionmedication-use behavior have also postulated an additionalpredictor that is not explicitly part of the Extended HealthBelief Model, concerns about or distrust in medications. Thisconstruct encompasses the findings from the previously qual-itative focus group studies that medications are sometimesperceived to be intrinsically harmful, that their use creates anundesirable state of dependence, that they compromise one’ssocial identity, and that generally the medical professionoveruses them. Concerns about or distrust in medications is aconstruct separate from actually experienced side effects.

Yood and colleagues found that those with a strong distrustof medications were only half as likely to fill a prescription fora fracture prevention medication at least once [71]. In McHor-ney’s study, beliefs that drugs are safe had a weaker


association with bisphosphonate compliance than beliefsabout medication effectiveness, but those in the lowest tertileof drug safety beliefs had an odds ratio of 2.26 for medicationnon-compliance compared with those in the top tertile ofmedication safety beliefs [70]. Schousboe and colleaguesreported that for each standard deviation increase in concernsabout medications, the odds ratio of self-reported non-persistence with bisphosphonate therapy was 1.39, and theodds ratio for self-reported non-compliance was 1.23 [72•].

Medication Use Self-Efficacy

Self-efficacy, defined as the belief that one is capable of actionthat can result in favorable outcomes, has been linked to betterhealth status and specifically to a sense of personal behavioralcontrol, more optimistic outcomes expectations, higher moti-vation to act, and greater effort to achieve the target behavior oroutcome [75]. Two studies have examined the associationbetween medication use self-efficacy and fracture preventionmedication adherence, and both found a positive association[72•, 76]. Self-efficacy appears to be associated with both self-reported persistence and even more strongly with compliancewith fracture prevention medication. In Schousboe’s study,those in the lowest quartile of medication-use self-efficacyaremore likely to be non-persistent, but there is little differencein persistence among those with self-efficacy better than thelower quartile. In contrast, those in the highest quartile of self-efficacy had an odds ratio of 0.09 for non-compliance com-pared with those in the lowest quartile [72•]. These findingssuggest that a mild level of self-efficacy is necessary for thepatient to maintain an active prescription for the medication,but that compliance with it improves further with higher levelsof self-efficacy.

Physician–Patient Relationship

In spite of access to medical information through friends,relatives, medical advocacy groups, and the internet, the phy-sician typically is in command of more knowledge and exper-tise than the patient and other lay people (a situation calledinformation asymmetry) [77]. Patients are often unable tofully independently confirm or refute information the physi-cian provides, and therefore the patient’s trust in the physicianmay have a significant association with acceptance of andadherence to medication recommended by that physician[78]. This is conceptualized by Hall to consist of trust in thephysician’s competence, that the physician considers thepatient’s interests paramount and is not following an agendacontrary to those interests, is honest, and will honor thepatient’s confidentiality [79]. One study of in-depth interviewswith 50 patients documented concerns among some of themthat the pharmaceutical industry unduly influences physicianprescribing habits such that the physician is in part, perhaps

unintentionally, looking after the pharmaceutical industry’sinterests and not just the patients [80].

Among patients with osteoporosis, Yood and colleaguesfound that trust in the physician was nearly associated withprimary adherence to fracture prevention medication (P-value equal to 0.07) but that this possible relationship dis-appeared when adjusted for medication effectiveness beliefsand distrust of medications [71]. Schousboe and colleaguesalso noted no direct association between trust in the physi-cian and self-reported bisphosphonate persistence or com-pliance when adjusted for perceived necessity formedication and concerns about medications. However, us-ing a path analysis, these authors noted that for each stan-dard deviation increase in trust in the physician, perceivednecessity for fracture prevention medication increases by0.27 standard deviations and concerns about medicationsdecrease by 0.26 standard deviations [73•]. Therefore, trustin physician did have a modest effect on self-reported per-sistence, but it is mediated by perceived necessity of fractureprevention medications and concerns about medications.

The concept of trust in the physician has been thought bysome to include patient perceptions of how well the physiciancommunicates with them, and patient satisfaction with thephysician’s decision making style. Open affiliative communi-cation refers to patient perceptions that the physician is dis-closing all relevant information about the target disease andmedication proposed to treat it, listens to the patient’s concernscarefully, and addresses all of the patient’s questions and con-cerns [81]. Physician decision making style has been concep-tualized as falling into 1 of 3 categories; the physician takes fullcharge of the medical decisions to be made, the patient takesfull charge and tells the physician what they want done, or amiddle category where the patient and physician share thedecision making and come to a consensus as to what to do[82]. The last category is called a Shared Decision MakingStyle. While the majority of patients in general prefer that theirphysician employ a shared decision making style, this prefer-ence may be dependent on the situation (eg, a preventive healthcare decision vs a medical emergency) and may change overtime [82]. Hence, patients’ congruence with and satisfactionwith the physician’s decision making style is conceptuallymore important to patient acceptance of the physician’s advicethan that physician’s decision making style per se [83].

In the path analysis of Schousboe et al. physician opencommunication from the patient’s perception and patient sat-isfaction with the decision making style of the physician werenot associated with perceived necessity of medication andconcerns about medication independent of trust, but werestrongly associated with trust in the physician [73•]. Hence,open communication and patient satisfaction with the physi-cian’s decision making style may be necessary for patients totrust their physician, and the effects of these 2 variables onmedication-use behavior may be indirect through trust in the


physician primarily and through medication beliefssecondarily.

A recent survey study suggests that patients and physiciansview the level of fracture risk at which fracture preventionmedication is appropriate quite differently. While the median10 year risk of hip fracture at which physicians thoughtfracture prevention medication should be prescribed was10 %, the median 10 year risk of hip fracture at which patientsthough fracture prevention medication should be taken was50% [84•]. Although physicians and patients rank-ordered theseverity of osteoporosis as a disease compared with otherchronic conditions (such as hypertension, breast cancer, dia-betes, and arthritis) similarly, it remains unclear if the patientsin this study had an accurate understanding of the quality oflife consequences of osteoporotic fractures.

Other Barriers to Medication Utilization: Medication Costs,Regimen Complexity, & Social Support

In survey studies, some patients state they stopped takingfracture prevention medication because of its cost [29, 49].Two studies have documented that prescription drug coverageis associated with choice of agent to treat osteoporosis [9, 85].Longitudinal quasi-experimental studies have consistentlyshown a reduction in medication utilization when out of pocketdrug costs increase through either elimination of prescriptiondrug coverage, or increases in medication co-pays, or co-insurance [86, 87].

Prescription for multiple additional medications is asso-ciated with lower persistence in with fracture preventionmedication in some [15, 16] but not all studies [88]. Regi-men complexity, defined as the number of prescribed med-ication doses per day, is associated with poor medicationcompliance [89, 90].

The association of various forms of social support withadherence to osteoporosis medications has not beenreported. Instrumental social support, defined as actions byothers that directly facilitate one’s use of medications (suchas putting medications out or giving reminders to takemedication), is associated with compliance to other medi-cations. This may be particularly important to sustain com-pliance among the cognitively impaired or frail elderly.

Where Do We Go from Here?

The phenomena of medication primary and secondary ad-herence, and of medication persistence and compliance arehighly complex but pervasive across multiple medicationsand the target conditions they treat, transcending specificmedications and target diseases. There is now a large bodyof evidence to suggest that medication non-compliance canbe intentional or unintentional [91], and that a substantial

proportion of medication non-persistence is a product ofpatients’ deliberate choices [92]. Therefore, understandingthe mental models of osteoporosis, fractures, and the med-ications recommended to reduce their risks of fractures thatpatients employ when weighing the risks and benefits oftreatment is critical if we are to make better progress reduc-ing non-adherence with fracture prevention medication.

There is much work yet to be done. First, patients maynot understand the clinical consequences of fractures, andstudies done to date have not addressed how well patientknowledge of fracture severity (especially hip and clinicalvertebral fractures) improves with education and counsel-ing. The degree to which lower health literacy and numeracymay be a barrier to patients’ understanding of their risks forand consequences of fractures has also not been adequatelystudied [93], yet there is evidence linking low health literacyto poorer ability to take medications appropriately [94].

Second, the role of time preference in patient decisionmaking regarding their health behaviors and choices regardinguse of medication has not been explicated [95]. Time preferencerefers to the degree to which individuals value future rewardsand costs compared with their present day value [96, 97].Conceptually, if a person is quite uncertain they will be alivein 5 years, they may place a much lower value on rewards andbenefits they may reap in 5 years compared with their presentday value [98]. Similarly, if a person’s current life circum-stances demand a lot of cognitive and/or physical effort toaddress current day problems, future rewards and costs maybe discounted substantially in their minds relative to currentday rewards and costs. When fracture prevention medication isprescribed, patients are essentially being asked to expend cur-rent day resources (time, money, etc) to prevent adverse eventsthat may or may not happen in the future. Hence, those whosetime preference de-emphasizes future rewards and costs rela-tive to the current day may theoretically place less value onmedications to prevent future adverse events.

Third, how patients arbitrage information about medica-tions from different sources (such as their health care pro-viders, other members of their social networks [eg, familyand friends], the internet, and various advocacy groups)have not been explicated. We do not know how patientsdevelop the attitudes and beliefs they have about medica-tions and the target conditions, nor do we know how muta-ble those attitudes and beliefs are.

Conclusion

Non-adherence to fracture prevention medication remains asubstantial barrier to efforts to reduce the societal burden ofosteoporotic fractures along with their associated costs andquality of life loss. Efforts to reduce non-adherence to fractureprevention medication thus far have, at best, been only


modestly successful. A long path of research and inquiry maybe required to better characterize and understand the phenom-enon in order to develop interventions that reduce non-adherence with better success than what has been tried to thisdate. Central to these efforts will be to understand the mentalmodels of their health status and of medications that patientsemploy when making medication use choices.

Disclosure The author reported no potential conflicts of interestrelevant to this article.

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adherence with medications used to treat osteoporosis: behavioral insights

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