Overcoming Problems with Adherence to Osteoporosis Medication

Véronique Rabenda; Jean-Yves Reginster


Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(6):677-689. 

In This Article

Strategies to Enhance Adherence with Osteoporosis Medication

Given the aging population and the burden of osteoporosis, there is increasing interest in the development of interventions to promote patient adherence with effective therapeutic regimens.

One potential way to improve adherence is to increase patient convenience by decreasing the frequency of dosing regimens. Today, the dosing regimen of osteoporosis medications varies from daily intake to yearly administration. Treatments with longer intervals between doses can offer greater convenience and potentially higher adherence in the real world compared with daily or weekly bisphosphonate therapy. However, simplification of the medication regimen is unlikely to completely solve the problem of nonadherence with treatment, but should be one component of a multifactorial strategy.

Increasing interaction between the healthcare providers and patients may be the most-effective intervention to improve compliance and persistence. In a systematic review of interventions designed to improve adherence and persistence with osteoporosis medications, few interventions were efficacious and no clear trends regarding successful intervention techniques were identified.[91] However, it appears that the most-efficacious intervention was a periodic follow-up interaction between patients and health professionals. In each of the interventions with statistically significant improvements in adherence, the intervention subjects received periodic one-on-one follow-up with trained healthcare professionals, whereas the control subjects did not. The intervention that demonstrated the greatest improvement in adherence employed an intervention whereby subjects participated in multiple counseling sessions with nurses.[92] In this study, nurses who were trained in motivational interviewing used monthly telephone calls to encourage adherence among women who were prescribed risedronate for the treatment or prevention of osteoporosis. Results showed that 69% of the intervention subjects were adhered persistently versus 41% of the control group. This counseling style has been incorporated into several effective medication adherence interventions for chronic conditions, including hypertension, HIV and asthma.[93–96] Additional studies of patients with chronic diseases, such as rheumatoid arthritis and asthma, show that face-to-face counseling from healthcare providers can improve adherence.[97,98]

Furthermore, patient education has been demonstrated to improve medication compliance and persistence, and should be considered an integral part of any disease management program. Cuddihy and colleagues described a prospective nonrandomized population-based study involving women with osteoporosis who had recent distal forearm fractures.[99] Soon after the fracture, patients were provided with educational materials, a physician appointment and a bone mineral density testing appointment. Assessment of patient adherence to treatment recommendations was conducted by a patient questionnaire at 6 months, where the patient was asked to report whether they were taking one of a list of medications for osteoporosis. For 38 women who were advised to begin therapy for osteoporosis, the intervention improved self-reported medication adherence at 6 months (36% were adherent compared with 9% in a historical cohort). Patient education combined with personal information from dual-energy x-ray absorptiometry scan results significantly increased calcium and vitamin D intake.[100–102] Women in the intervention group were significantly more likely to report that they had modified their diet, calcium and vitamin D intake than women in the control group, who were not exposed to education.[102] Guilera et al. utilized an educational leaflet containing general osteoporosis information, which was distributed to a group of patients starting raloxifene.[103] However, the difference in raloxifene compliance, as assessed by the Morisky test, between the intervention and control group did not differ significantly at 12 months (47 and 53%, respectively).

In the Persistence Study of Ibandronate versus alendronate (PERSIST) study, Cooper et al. compared monthly ibandronate plus a patient-support program with weekly alendronate without a support program.[104] The patient-support program included information regarding osteoporosis and monthly reminder phone calls from nurses who provided dosing instructions and osteoporosis information, and stressed the importance of adherence. At 6 months, 75% of the ibandronate users were adherent (i.e., collecting at least five out of six prescriptions) versus 68% of the alendronate users. Cooper et al. reported that 57% of intervention subjects persisted with therapy (number of days from study entry to the date of the first failure to persist − where failure to persist is missing a month's prescription or withdrawal from the study). While this percentage was suboptimal, it was significantly better than in the control group (39%). In another study, it was shown that among 5413 postmenopausal women enrolled in an education and follow-up program, the persistence rate (defined as the percentage of patients still on treatment at the end of the 18-month course) to teriparatide was 81.5% at 18 months.[105] The authors stated that this high rate of persistence was due to the education and follow-up program. In a more-recent study, it was shown that an educational program increased knowledge regarding osteoporosis and increased self-reported adherence to pharmacological treatment over a period of 2 years.[106] In this particular study, a total of 300 patients were randomized to either an osteoporosis school program (four classes of eight to 12 participants over 4 weeks) or a control group. The program was conducted by a multidisciplinary team of health professionals. In each session, as a starting point, the teaching took note of the patients' everyday lives, individual experiences and needs. The change from baseline in knowledge score at 3 months was significantly higher in the school group than in the control group and the knowledge score remained significantly higher in the school group at both 12 and 24 months. Adherence (defined as patients taking their medicine correctly at the appropriate time) with pharmacological therapy at 24 months was significantly higher in the school group compared with the control group (92 vs 80%; p = 0.006).

Moreover, some studies have suggested that implementing monitoring or giving feedback to patients, such as bone turnover markers or bone mineral density information, as a tool to improve long-term adherence, may result in improved outcomes for patients with postmenopausal osteoporosis.[107,108] Clowes et al. showed that monitoring therapy by a nurse with or without assessment of bone resorption markers increased compliance by 57% and persistence by 25% compared with no monitoring.[107] In this study, the intervention included a nurse follow-up office visit at 12, 24 and 36 weeks after initiation of treatment. The nurse used a structured interview containing six open-ended questions related to the patient's well-being, problems with their osteoporosis medication (raloxifene) and adverse events. In addition to the nurse follow-up, a third group received feedback concerning levels of urinary-N-telopeptide (NTX), a bone-remodeling marker (with a >20% decrease being taken as a satisfactory response). Adherence was defined as the percentage of medication taken over 1 year and was considered satisfactory when greater than 75%; persistence was defined as taking the medication for 1 year with no 15-day period showing more than 50% of missed doses. A nonspecific trend toward better adherence in the nurse-monitoring group (84%) was noted compared with the marked-monitoring group (75%) and the no-monitoring group (74%). Monitoring (nurse or marker) increased the adherence rate by 57% (p = 0.04): adherence was unsatisfactory in 58% of patients in the no-monitoring group, 37% of those in the marker-monitoring group and 32% of those in the nurse-monitoring group. Patients with a good NTX response increased their adherence by 140% compared with nonresponders in the marker-monitoring group (p = 0.03), by 92% compared with the no-monitoring group (p = 0.04) and by only 18% compared with the nurse-monitoring group (not significant). Persistence increased by 25% with monitoring (nurse only or marker) compared with no monitoring (p = 0.07). The results of this study support monitoring by a nurse to improve adherence with osteoporosis medications.

In the Improving Measurements of Persistence on Actonel Treatment (IMPACT) trial, Delmas et al. investigated whether communicating the results of NTX assays at 10 and 22 weeks influenced adherence to risedronate treatment.[108] The patients were randomized to information or no information regarding the NTX assay results. Patients in the information group were told that they had a good response (positive message) if their NTX level dropped by more than 30%, some response (somewhat positive message) if their NTX level differed by less than 30% in either direction from the baseline value, or no response (negative message) if the NTX level increased by more than 30%. An electronic device was used to count the number of tablets taken. Persistence was similarly high in the two groups (80 and 77% with and without information, respectively). Persistence varied according to the NTX response. Thus, receiving a positive message (NTX decrease >30%) was associated with a 29% decrease in the risk of treatment discontinuation compared with receiving no information. On the other hand, a negative-message group (NTX increase >30%) was associated with a relative risk of 2.22 for treatment discontinuation compared with the no-information group. Finally, a somewhat positive message (NTX within 30% of baseline) had no effect on adherence compared with no information.

Moreover, compliance with physician-recommended treatments for osteoporosis may be greater among women apprised of their fracture risk following bone densitometry testing.[109] In a survey of women who received testing, those who reported that their bone density measurements were below normal were significantly more likely than women with normal results to begin the recommended preventive treatment (94 vs 56%; p ≤ 0.01), to start hormone therapy (38 vs 8%; p ≤ 0.01) and to take preventive measures to avoid falling (50 vs 9%; p ≤ 0.01).[109]

It is important, at the time of diagnosis or at the time of the initiation of treatment, that healthcare providers give adequate information to patients about the diagnosis, risk factors, consequences of illness and prognosis. For agents with complicated dosing guidelines, such as bisphosphonates, patients must be taught to take their medication in accordance with instructions to reduce the likelihood of adverse effects. Provision of appropriate information to patients regarding how to cope with the adverse effects of treatments in particular could change patients' attitudes towards treatment and improve adherence. In patients with existing fractures, strategies to manage both the physical and psychosocial burdens imposed by disability should be proposed.

Lastly, health professionals can enhance compliance and achieve desired outcomes by adopting patient-centered approaches and by involving patients as partners in the management of their condition.[110,111] This enables patients to take a more-active role in their treatment, which promotes compliance and enhances patient satisfaction and outcomes. As with any therapeutic decision, physicians must ensure that the specific therapy for each patient is custom tailored to their preferences. Although the special requirements for taking bisphosphonates (e.g., timing of the dose and fasting) cannot be modified, problems regarding the frequency of dosing could be addressed by offering patients the choice of how often they would prefer to take their medication. These preferences may be based on patients' lifestyles and needs. This active participation in treatment decisions will likely improve compliance. In a randomized controlled trial, patients with poorly controlled asthma who contributed in making decisions regarding their treatment showed significantly better adherence to asthma treatment.[112] In this study, patients assigned to the shared decision-making group participated in a process to elicit their goals for their asthma treatment and their priorities regarding their asthma medications, and then engaged in a process of shared decision making with the care manager, which was designed to arrive at a prescribed regimen that satisfied their goals and preferences. Compared with usual care, using the shared decision-making process resulted in significantly better compliance (67 vs 46%; p < 0.0001) as well as significantly better clinical outcomes (asthma-related quality of life, healthcare use, rescue medication use, asthma control and lung function). In one study of ibandronate compared with other bisphosphonates, increasing patient participation in determining treatment options was associated with improved patient adherence.[113] In addition, involving the patient's whole family may create the social support system needed to improve compliance with therapy.


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