Medical Therapy for Osteoporosis and Approaches to Improving Adherence
Some patients restart osteoporosis therapy after a prolonged lapse in medication use. In one study, re-initiation rates for bisphosphonate therapy among persons who discontinued were as high as 30% within 6 months and 50% within 2 years [44]. Predictors of treatment re-initiation included younger age, female sex, history of fracture, recent hip fracture, nursing home discharge, and BMD testing [44].
Factors that Impact Adherence
Understanding which patients are most likely to be compliant with medications can aid physicians when monitoring osteoporosis treatment responses. In a retro-spective claims analysis, older age was found to be a predictor of compliance: women 65 years and older were more likely to be compliant than younger patients (P = 0.012) [45]. Among women receiving denosumab, improved adherence was found among women with a family history of a parent with a hip fracture, and lower adherence was seen in those with higher age, decreased mobility, and further distance from the clinic where the medication was provided [46].
Major reasons for nonadherence include a fear of potential side effects, occurrence of real side effects, the complicated dosing regimens, and perceived lack of benefit from the medications due to the asymptomatic nature of osteoporosis. In the above noted observational study from the U.K., more than half of the nonadherent patients attributed their nonadherence to side effects (53.9%), with a smaller proportion reporting fear of potential side effects (20.5%) or trouble with the dosing regimen (8.0%)[42].
Patients may also be unwilling to continue to take an osteoporosis medication if a fracture develops while on it and if they are not otherwise provided evidence that the medication is working. In a study by Costa Paiva et al, an understanding and knowledge to osteoporosis was a prerequisite to adherence and the strongest predictor of knowledge was higher education level [47]. Factors that impaired adherence were lower socioeconomic status and presence of comorbidities [47]. In a phenomenological qualitative study, trust in a health care provider was the most common reason for patients’ decision to accept an osteoporosis medication, emphasizing the importance of physician-patient communication [48].
Interventions to Enhance Adherence
Current methods of improving adherence for chronic health problems are mostly complex and not very effective [49]. In a systematic review of interventions to improve medication adherence, only 37 out of 81 studies reported improved adherence in the treatment of chronic diseases, and multifaceted treatments were more likely to succeed [49]. Improving adherence to osteoporosis medications is a complex issue, and a number of interventions evaluated in systematic reviews have shown limited efficacy [50,51]. Simplification of dosing regimens have been found to have a significant impact in chronic disease management [52,53] as well as in some studies of osteoporosis medications.
Simplification of Dosing
Among women prescribed daily vs. weekly bisphosphonates, those on the weekly regimen had significantly higher compliance [54]. However, rates were suboptimal in both groups and more than 50% of women discontinued at 1 year [54]. In addition, in a meta-analysis of osteoporosis medication adherence, a nearly two-fold higher odds of discontinuation with daily vs. weekly bisphosphonates was seen (odds ratio 1.90, 95% CI 1.81–2.00) [55]. Likewise, in a retrospective study in Spain, nearly 85% of those started on a daily bisphosphonate stopped within a year [56], while discontinuation was significantly lower in those prescribed a weekly or monthly bisphosphonate or daily teriparatide; however, discontinuation was still nearly 50% in these groups [56].
Once monthly dosing may be preferred by some patients as there is less time involved in thinking about the disease being treated and a perception of lower likelihood of side effects. In one study, postmenopausal women who had previously stopped oral bisphosphonates due to GI side effects had high adherence rates after self-selecting either monthly oral or quarterly intravenous ibandronate therapy [57]. However, not all studies show significant differences in adherence between weekly and monthly preparations [58–60].
The newer parenteral treatment options that can be given every 6 months or once yearly have the potential to significantly improve adherence. Once a year parenteral administration of a bisphosphonate was preferred over once-weekly oral administration, according to a 1-year study in patients with low bone density previously treated with alendronate [61]. A recent study that looked at persistence with an infusion of zolendronic acid in Taiwanese patients for 48 months found that 85% of patients received at least 2 infusions [62]. In patients treated with denosumab in 4 European countries, adherence and persistence at 12 months were consistently > 80% [46]. Persistence in this study was defined as receiving the subsequent injection within 6 months ± 8 weeks of the previous injection; adherence was defined as receiving 2 consecutive injections within 6 months ± 4 weeks of each other [46].
In a study by Cramer et al, increased adherence and persistence was seen with weekly alendronate compared daily alendronate at the end of 12 months [54]. Similar results were seen in a large longitudinal cohort study of weekly vs. daily bisphosphonates but less than 50% of patients were adherent with the weekly regimen [63]. When once monthly preparations of bisphosphonates became available, studies continued to support a patient preference for less frequently dosed bisphosphonates, with the majority of patients preferring monthly over weekly dosed medications [64–66].
The availability of quarterly ibandronate and yearly zoledronic acid infusions have further simplified dosing. In large, randomized, multicenter studies, patients consistently expressed a preference for yearly infusions over a weekly oral medication [61,67]. Adherence and persistence to osteoporosis medications was also greater in women receiving intravenous ibandronate compared to those receiving oral alendronate [68,69]. However, a study by Curtis et al showed low persistence with intravenous bisphosphonates in a Medicare population [70]. A possible reason for the lower adherence in this population was postulated to include the provision of the infusions at an outpatient center rather than a physician office. Automated nursing reminders with either phone calls or emails have the potential to mitigate the problem of persistence with this less frequent regimen [71,72]. In a review of patient preferences, less frequent dosing of medications was a common desire, but further generalizability were limited, emphasizing the need to individualize treatment [73].
Patient-Provider Communication
Individualizing treatment with better patient-provider communication and identification of potential barriers may increase compliance [74]. In one study, increasing patient participation in determining the treatment option was associated with improved patient adherence [57]. A systematic review of literature on interventions to improve adherence found that periodic follow-up interaction between patients and their health professionals also improved adherence [50]. Positive reinforcement via physician-patient discussion of either bone turnover markers or bone mineral density test results has also been found to improve long-term adherence with osteoporosis medications [71,75].
Better perceived physician knowledge may help with patient adherence. A study by Pickney et al reported that the patient confidence in their health care providers has influence on improved adherence, and patients were more likely to comply when the medications were prescribed by a specialist rather than a general practitioner [76].
