Overcoming Problems with Adherence to Osteoporosis Medication

Véronique Rabenda; Jean-Yves Reginster


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

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Expert Commentary

Adherence rates are universally poor for self-administered medications and chronic diseases regardless of disease type, severity and accessibility to resources. Evidence suggests across multiple therapeutic areas that many patients take drugs incorrectly, infrequently or not at all. The association between nonadherence and increased healthcare resource utilization and costs, and nonadherence and suboptimal health outcomes has been found within and across chronic diseases.[114–121] It is not surprising that poor adherence also extends to patients receiving osteoporosis medications. Therefore, pursuing interventions that can improve adherence is worthwhile.

A consistent finding with other chronic diseases, including depression, diabetes, hypertension and asthma, is that having a simpler regimen and fewer medications to administer is associated with improved adherence.[201] Today, clinicians and patients have a wide number of options to tackle the treatment of osteoporosis. Treatments are available in different formulations with various modalities, dosages and frequencies of administration, offering a wider option of choices to suit patients' and clinicians' preferences and needs. They include, among others, once-monthly oral, quarterly or annual intravenous bisphosphonates, or subcutaneous, twice per year denosumab. Their potential advantages include more-convenient administration and reduced dosing frequencies. Studies reported that adherence to these treatments is superior compared with the weekly or daily regimens.[30–35] These differences are expected to have major repercussions on fracture prevention in osteoporotic women using such treatments. Moreover, most patients report that they prefer these low-frequency dosing regimens.[30–35] However, as mentioned already, results from preference surveys comparing different dosing regimens should be interpreted with caution because the source of study funding may not be unbiased. Moreover, overall levels of preference and satisfaction with these intermittent regimens may be higher than in the community setting based on the self-selection of patients in these studies. As with all studies of preference, the willingness of patients to accept the treatments offered can potentially confound the interpretation of the results. To our knowledge, there are no available published data from large-scale observational studies on compliance or persistence, except for on monthly ibandronate. Consequently, the findings should be confirmed in real-life settings. Concerning strontium ranelate, the administration requirements of once-daily strontium ranelate (±2 h after a meal, preferably at bedtime) are less complex and inconvenient than those of oral bisphosphonates, which may confer an advantage in terms of patient adherence to therapy, although this has not yet been addressed formally. Moreover, strontium ranelate is taken orally as a suspension in water, which some patients, particularly the elderly, may find easier to swallow than agents in tablet formulation. In particular, the results of the Richards et al. study showed that very few subjects were uncomfortable with taking half a glass of water prior to bedtime.[28] Moreover, a large proportion of respondents preferred a medication that does not require them to fast and remain upright after taking the medicine. These results suggest that among subjects in the age group most often afflicted with osteoporosis, daily therapy may be more preferable to weekly or monthly therapy, if there is little inconvenience associated with the taking of the medication. Studies comparing strontium ranelate with other agents with regard to patient adherence would certainly be of interest.

Thus, the availability of multiple oral and intravenous options gives patients the opportunity to decide which attributes of a regimen they consider most important for long-term sustainability.

In addition, intermittent intravenous administration avoids the problems of reduced bioavailability and upper gastrointestinal adverse events. These are particularly useful for patients who cannot adhere to strict oral dosing requirements or experience gastrointestinal adverse events with oral agents. Infusions of these agents ensure adherence throughout the entire dosing period (3 months for ibandronate and 12 months for zoledronic acid).[122]

The benefits of longer dosing intervals and increased compliance may extend beyond pure clinical considerations. As demonstrated by recent modeling studies, a less-frequent drug regimen that improves persistence would be more cost effective.[76,123] Although greater persistence increased drug costs in this model, other medical costs were reduced by decreasing the likelihood of fractures, more so than offsetting the increased drug expenditures.[123] However, it is unclear what the adherence with such regimens will be after the first year. The impact of these new formulations on persistence and compliance in real-life settings remains to be determined. Moreover, the extension of dosing intervals increases the importance of full compliance with therapy because the therapeutic consequences of missing a monthly or quarterly dose may be more substantial than with a weekly or daily dose.

While medications with less-frequent dosing intervals and intravenous administration may reduce nonadherence, simplification of medication regimens should be one component of a multifactorial strategy.

Some authors suggested the utility of biochemical markers or bone mineral density measurements to provide patients with feedback on treatment effectiveness.[107,108] However, measurement of biochemical turnover markers with feedback does not significantly improve adherence to therapy in women with osteoporosis, although the opportunity for the patient to discuss therapy with a health professional is likely to be beneficial. Bone marker information has traditionally been given as a percentage change, a format that is not user friendly for most patients. The fact that test results are generally not available at the time of the encounter with the healthcare professional also presents a substantial challenge in providing feedback to patients. Often, the results are available several weeks later and may be sent by mail or discussed by phone. Moreover, the impact of offering densitometry may be limited, since most patients stop their treatment within the first 6 months of prescription, an interval in which bone densitometry is neither recommended nor proposed.[124]

Current methods of improving adherence to treatments for chronic diseases, such as osteoporosis, are complex and have limited effectiveness. A systematic review reported that less than half of interventions designed to improve adherence were associated with statistically significant improvements in medication adherence or treatment outcomes.[125] In addition, recent studies found that these interventions in patients with chronic conditions are not cost effective.[126] It has been reported that the most effective medication adherence interventions typically utilize multifaceted approaches.[125] This seems logical and particularly relevant to osteoporosis therapy since determinants of poor adhrence vary widely among patients. As such, it is unrealistic to expect that a one-dimensional intervention could significantly improve adherence across a diverse population.

Strategies to improve adherence to medications should be individualized. Therefore, it is important for healthcare providers to understand why nonadherence to osteoporosis medications occurs. However, there are no known clinical features that identify individuals who are likely to be poor adherers. We need to better understand the process by which patients form intentions to take or not take recommended medications. Moreover, at the time of limited healthcare resources, patients most at risk for poor compliance should be identified and targeted for interventions in order to focus resources on those who are most in need. Means to help healthcare providers to identify patients who are at high risk of poor adherence should be developed. The use of questionnaires or reviewing adherence to other chronic medications may be helpful.[127,128] Future studies are needed to improve our knowledge and to examine the factors associated with treatment discontinuation or poor treatment compliance. This understanding will likely help us to design intervention strategies that make the appropriate interventions possible, thereby improving patient adherence and the effectiveness of treatments for osteoporosis.

Finally, in addition to adherence, a continuing challenge in the management of osteoporosis is the underdiagnosis and undertreatment of the disease. Despite the availability of expert guidelines on the diagnosis and treatment of osteoporosis,[129] several studies in different countries have observed that a significant proportion of patients did not receive any treatment for osteoporosis even after a fracture.[36–38,130–133] Most importantly, most of the patients who were treated following a fracture reported low adherence rates.[36–38] A major reason for the underdiagnosis of osteoporosis is that the most-common osteoporotic fractures – vertebral fractures – are asymptomatic and therefore go unrecognized by the patient and physician. Healthcare providers should be educated about the need to identify patients with osteoporosis and prescribe osteoporosis medications. Additionally, they need to be conscious of problems with adherence and the need to monitor and support their patients in this important task.


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