Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women

Abstract

Aims: To evaluate the association between noncompliance with alendronate and risedronate and the risk of nonvertebral osteoporotic fracture in community-dwelling elderly women.

Methods: A nested case-control study was conducted using the Quebec administrative health databases. To be included in the cohort, women needed to be aged > or = 68 years and to have initiated treatment with alendronate or risedronate between 1 January 2002 and 31 March 2005. Cases consisted of all women with an incident nonvertebral osteoporotic fracture occurring > or = 1 year after initiation of therapy. Each case was matched with up to 20 controls using incidence density sampling, according to age (+/- 1 year) and follow-up duration. A woman was noncompliant if she had a medication possession ratio (MPR) <80% for total follow-up duration. Rate ratios (RR) for fracture were estimated through conditional logistic regression analysis, adjusting for potential confounders.

Results: Among the 30 259 women included in the cohort, 1036 nonvertebral fracture cases were identified and were matched to 20 069 controls. Compared with women with a MPR > or = 80%, those with a MPR < 80% had a greater risk of nonvertebral fracture [adjusted RR 1.27, 95% confidence interval (CI) 1.12, 1.44]. Considering hip fracture only, the multivariate model yielded similar results, (adjusted RR 1.28, 95% CI 1.02, 1.61).

Conclusions: Among community-dwelling elderly women, noncompliance with alendronate or risedronate is associated with an increased risk of nonvertebral fracture.

Figure 1

Association between noncompliance and nonvertebral fracture for different ranges of MPR (n = 21 105). RR, rate ratio; MPR, medication possession ratio; reference was MPR ≥ 90% (RR = 1.00). For 50% ≤ MPR < 90%: adjusted RR 1.23 [95% confidence interval (CI) 1.05, 1.44]; for MPR < 50%: adjusted RR 1.29 (95% CI 1.11, 1.50). Adjusted for variables listed in Table 1 that were selected by backward procedure (the variable MPR < 80% was forced in the model a priori): bone mineral density (BMD) test, diagnostic code for osteoporosis, prior osteoporotic fracture, dementia, hyperlipidaemia, coronary artery disease, peripheral vascular disease, prior hospitalization, use of anticonvulsants, use of opiates, use of antidepressants

Figure 2

Rule-out approach sensitivity analysis to assess the strength of residual confounding necessary to fully explain the observed association between noncompliance and nonvertebral fractures. The area at the right (zone B) of the curve shows combinations of associations between confounder-fracture and confounder-noncompliance that would induce confounding by an unmeasured variable strong enough to have elevated the association between noncompliance and fracture risk (95% Cl 1.12–1.44, - - -) from the null value (RR = 1) to the observed point estimate (RR = 1.27, ——). The area at the left of the curve (zone A) represents combinations that would not be strong enough to bias the observed RR. The prevalence of the confounder was assumed to be 20% and the prevalence of women with a medication possession ratio (MPR) < 80% was 41%.