Medical Therapy for Osteoporosis and Approaches to Improving Adherence

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].