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Persistence with bisphosphonates

Systematic review

Bandolier looks for good information on persistence (compliance, concordance, adherence, whatever) because medicines work better in the patient than in the blister pack. For so many long-term therapies persistence is awful. With bisphosphonates one reason is the boring way bisphosphonates have to be taken; fasting overnight, taken alone, lots of water, no other food of drink and remaining upright for 30 minutes. Lack of motivation in an asymptomatic disease contribute to the 'why bother?' factor. A systematic review [1] shows that reducing hassle improves persistence.

Systematic review

The review looked at a single database (1998-2006) for anti-osteoporosis medicines using terms relating to compliance or persistence. Studies had to have one measure of compliance or persistence derived from administrative databases with patient demographic and prescription information.

Compliance (defined as the extent to which a patient acts in accordance with the prescribed interval and dose as well as dosing regimen) was measured as the medication possession ratio (MPR). This is the number of days' supply received over the length of the follow up, and is described as a ratio. Persistence (defined as the accumulation of time from initiation to discontinuation of therapy) was measured as the number of days of possession without a gap in refills, and the percentage of patients.


Most of the therapies in the 14 studies obtained were for oral daily or weekly bisphosphonates. Studies had observation periods mainly of one year, with some longer. Results for daily or weekly bisphosphonates are shown in Table 1. All of the compliance and persistence outcomes were better for weekly than daily bisphosphonates. Clearly this was obvious to most prescribers, as the number of persons prescribed weekly bisphosphonates was five times higher than those prescribed them daily.

Table 1: Daily and weekly bisphosphonate

Number of subjects
Medication possesion ratio (MPR)
Persistence (days)
Persistence (%)

While Table 1 shows the average results weighted by number of patients, Figure 1 shows the individual study results for the percentage of patients compliant, which was consistently higher for weekly than daily use.

Figure 1: Individual study results


Not earth shattering, but solid evidence that making things easier for patients can help. The paper has an interesting discussion about how different methods of measuring persistence and compliance can affect results, all of which is interesting. The simple fact, though, is that weekly bisphosphonates resulted in higher use. It is likely that high compliance and persistence are needed to minimise fracture risk.


  1. JA Cramer et al. A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporosis International 2007 DOI 10.1007/s00198-006-0322-8.

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