Abstract
Summary
Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for ≥2 years, the risk of hip fracture was increased after discontinuation, although with higher compliance and a longer duration of preceding bisphosphonate therapy, this risk was attenuated.
Introduction
Recent data suggest that hip fracture risk was not significantly increased among women receiving 5 years of bisphosphonate therapy who were subsequently randomized to placebo. We studied older women compliant with bisphosphonates ≥2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation.
Methods
Using administrative databases from a large U.S. healthcare organization, we identified women initiating bisphosphonate therapy compliant (Medication Possession Ratio, MPR ≥66%) for 2 years. We examined the rate of hip fracture among women who discontinued bisphosphonates versus those who remained on therapy.
Results
At 2 years, 9,063 women were eligible for analysis. Hip fracture incidence among women who discontinued bisphosphonates versus those who did not was 8.43 versus 4.67 per 1000 person years (p = 0.016). The adjusted hazard ratio of hip fracture per 90 days following discontinuation was 1.2 (1.1–1.3). For women with higher compliance at 2 years (MPR ≥80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation.
Conclusions
The rate of hip fracture was increased among women compliant with bisphosphonate therapy for 2 years who subsequently discontinued, suggesting that discontinuation is not advisable under these conditions. This association was attenuated with higher compliance and a longer duration of previous bisphosphonate therapy.
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Conflicts of interest
The authors make the following disclosures:
J.R.C.: grant support: Merck, Procter & Gamble, Lilly, Roche, Amgen, Novartis; consulting/honorarium: Merck, Procter & Gamble, Roche, Lilly
A.O.W.: grant support: Novartis
H.C.: grant support: Amgen
E.D.: grant support: Amgen
K.G.S.: grant support: Merck, Procter & Gamble, Lilly, Amgen, Novartis, Roche; consulting/honorarium: Merck, Procter & Gamble, Lilly, Amgen, Novartis, Roche
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Funding This project was funded by Novartis Pharmaceuticals and the Arthritis Foundation. The investigators also receive support from the National Institutes of Health (AR053351, AR052361). The authors independently developed the analysis plan, extracted the data, conducted the analysis, and interpreted the results.
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Curtis, J.R., Westfall, A.O., Cheng, H. et al. Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday. Osteoporos Int 19, 1613–1620 (2008). https://doi.org/10.1007/s00198-008-0604-4
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DOI: https://doi.org/10.1007/s00198-008-0604-4