Inaccurate self-reported data on medication exposure lead to less reliable study findings. From 2013 to 2015, we assessed the validity of information on medication use collected via a mailed medication inventory among 223 Women's Health Initiative participants who were members of a health-care delivery system. Self-reported information on medication use was compared with pharmacy records for statins, calcium channel blockers, β-blockers, and bisphosphonates. We assessed sensitivity, specificity, and positive predictive value (PPV) for current medication use. We assessed agreement on duration of use (<2, 2, 3, 4, or ≥5 years) by means of the weighted κ statistic. The mean age of participants was 77 years. Statins, β-blockers, and calcium channel blockers were each reported by over 15% of women, and bisphosphonates were reported by 4.5%. Compared with pharmacy records, the sensitivity, specificity, and PPV for self-reported use of statins, β-blockers, and calcium channel blockers were all 95% or greater. The sensitivity and PPV for bisphosphonate use were both 80% (95% confidence interval: 44, 97), and specificity was 99% (95% confidence interval: 97, 100). The κ statistic for duration of use was 0.87 or greater for all 4 medication classes. Compared with pharmacy records, self-reported information on current medication use and duration of use collected via mailed medication inventory among older women had almost perfect agreement for use of statins, β-blockers, and calcium channel blockers.

Objectives

To examine the association between long-term bisphosphonate use and fracture in older women at high risk of fracture.

Design

Retrospective cohort.

Setting

Women's Health Initiative.

Participants

Older women who reported at least 2 years of bisphosphonate use in 2008-09 (N = 5,120).

Measurements

Exposure data were from a current medications inventory. Outcomes (hip, clinical vertebral, wrist or forearm, any clinical fracture) were ascertained annually. Using multivariate Cox proportional hazards models, the association between duration of bisphosphonate use (3-5, 6-9, 10-13 years) and fracture was estimated, using 2 years as the referent group.

Results

On average participants were 80 years old and were followed for 3.7 ± 1.2 years. There were 127 hip, 159 wrist or forearm, 235 clinical vertebral, and 1,313 clinical fractures. In multivariate-adjusted analysis, 10 to 13 years of bisphosphonate use was associated with higher risk of any clinical fracture than 2 years of use (hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.07-1.57). This association persisted in analyses limited to women with a prior fracture (HR = 1.30, 95% CI = 1.01-1.67) and women with no history of cancer (HR = 1.36, 95% CI = 1.10-1.68). The association of 10 to 13 years of use, compared with 2 years of use, was not statistically significant for hip (HR = 1.66, 95% CI = 0.81-3.40), clinical vertebral (HR = 1.65, 95% CI = 0.99-2.76), or wrist fracture (HR = 1.16, 95% CI = 0.67-2.00).

Conclusion

In older women at high risk of fracture, 10 to 13 years of bisphosphonate use was associated with higher risk of any clinical fracture than 2 years of use. These results add to concerns about the benefit of very long-term bisphosphonate use.

Objective

The aim of the study was to examine the association of long-term oral bisphosphonate use, compared with short-term use, with fracture risk among postmenopausal women with breast cancer.

Methods

We studied 887 postmenopausal women who were enrolled to the Women's Health Initiative from 1993 to 1998, diagnosed with breast cancer after enrollment, and reported current oral bisphosphonate use of 2 years or more on a medication inventory administered in 2008 to 2009. The outcome of any clinical fracture was ascertained by self-report on an annual study form; a subset of fractures was confirmed with medical records. Women were followed from completion of the medication inventory until 2014. The association between duration of bisphosphonate use reported on the medication inventory and fracture was estimated using multivariate Cox proportional hazards survival models that compared 4 to 7 years and 8 or more years of bisphosphonate use with 2 to 3 years of use.

Results

On average, women were 76 years of age and were followed for 3.7 (SD 1.1) years. There were 142 clinical fractures. In the multivariate-adjusted analysis for fracture risk factors, 8 or more years of bisphosphonate use was associated with higher risk of fracture compared with 2 to 3 years of use (hazard ratio, 1.67 [95% CI, 1.06-2.62]). There was no significant association of 4 to 7 years of use with fracture.

Conclusions

Bisphosphonate use of 8 or more years was associated with higher risk of any clinical fracture compared with 2 to 3 years of use. Our findings raise concern about potential harm or decreased effectiveness of long-term bisphosphonate use on fracture risk. The findings warrant confirmatory studies.