Participants were identified by dispensing records. Patients were defined as persisters if they filled their prescriptions at least five times in 17 months. The researchers used a 57-item survey to assess reasons for persistence with bisphosphonate therapy. The final sample included 377 patients who persisted on weekly alendronate and 190 who persisted on monthly ibandronate.
Belief in the drugs' efficacy and the absence of side effects were strong determinants of persistence with bisphosphonates. In all, 93% of weekly persisters reported belief in the drug's effectiveness, versus 88% of monthly persisters. In both groups, 83% reported no side effects.
However, weekly persisters reported fewer side effects, more positive beliefs about drug safety and efficacy, and fewer osteoporosis concerns than monthly persisters did. Altogether, 45% of weekly persisters and 52% of monthly persisters reported cost to be a problem, and 37% of weekly persisters and 35% of monthly persisters reported that remembering to take the drugs was a problem.
Just 13% of weekly persisters and 7% of monthly persisters cited dosing frequency as a problem. Compliance is key because bioavailability is poor even under optimal conditions, when instructions are followed perfectly. Relative to a reference intravenous dose, the mean oral bioavailability of alendronate in women is 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and 2 hours prior to breakfast. Mean oral bioavailability is 0.63% for 30 mg of risedronate and 0.6% for 2.5 mg of ibandronate.
But optimal conditions are demanding. Patients are instructed to take the drugs with plain water first thing in the morning and at least 30 minutes before food, beverages, or other medications. In addition, they are instructed not to lie down for 30 minutes after dosing. Patients on ibandronate are advised to take the drug at least 60 minutes before the first food or drink in the morning and before taking any oral medications or supplements, including calcium, antacids, and vitamins. These patients are instructed not to lie down for 60 minutes after dosing.
However, even when those instructions are followed, patients don't completely maximize bioavailability, which improves the longer patients wait before eating. For 10 mg alendronate, bioavailability is reduced by approximately 40% when taken either 30 minutes or 1 hour before breakfast, versus dosing 2 hours before eating. The package labeling for alendronate notes “bioavailability was negligible whether alendronate was administered with or up to two hours after a standardized breakfast.” Drinking coffee or orange juice at the time alendronate is taken cuts bioavailability by approximately 60%.
For risedronate, the extent of absorption of a 30-mg dose when administered 30 minutes before breakfast is reduced by 55%, versus dosing while fasting. For ibandronate, the oral bioavailability is reduced by about 90% when taken with breakfast, versus when taken in fasting patients. Both bioavailability and the effect on bone mineral density are reduced when food or beverages are consumed less than 60 minutes after an ibandronate dose.