Kouta Ito, MD, MS
Do proton-pump inhibitors (PPIs) reduce the effectiveness of alendronate for preventing hip fractures? Is the effect dependent on PPI dose?
Cohort study using linkage of the National Hospital Discharge Register and National Prescription Database, with a mean follow-up of 3.5 years. Analyses assumed 100% refill compliance for alendronate.
38 088 patients ≥ 35 years of age (mean age 70 y, 83% women) who started alendronate between 1996 and 2005 (index date = date of first prescription for alendronate) and had not previously filled a prescription for antiosteoporotic drugs (bisphosphonates, selective estrogen-receptor modulators, parathyroid hormone analogues, or strontium ranelate).
Use of PPIs at baseline (prescription filled ≤ 12 mo before index date) or concurrent with alendronate (prescription filled during first 36 mo of treatment with alendronate).
Fractures of the hip (neck or intertrochanteric femur), spine, forearm, or humerus.
18% of patients used PPIs at baseline, and 27% used PPIs concurrently with alendronate during follow-up. 5.4% of patients had hip fractures, 1.5% had forearm fractures, 0.9% had humerus fractures, and 0.6% had spine fractures. Concurrent use of PPIs was associated with reduced effectiveness of alendronate for preventing hip fractures compared with no PPI use (Table); PPI use did not attenuate the effectiveness of alendronate for preventing forearm (4.5/1000 patient-y in PPI users vs 4.3/1000 patient-y in nonusers), humerus (2.9 vs 2.5/1000 patient-y), or spine (2.7 vs 1.3/1000 patient-y) fractures. In patients who used PPIs concurrently with alendronate, reduction in risk for hip fractures attenuated in a dose-dependent manner and was maintained only at lower cumulative PPI doses (cumulative defined daily doses [DDDs] 1 to 359, n = 7210, hazard ratio [HR] 0.63, 95% CI 0.55 to 0.72; DDDs 360 to 719, n = 1701, HR 1.00, CI 0.70 to 1.45; DDDs ≥ 720, n = 1266, HR 1.24, CI 0.71 to 2.18). Effectiveness of alendronate for reducing hip fractures was attenuated by PPI use in patients ≥ 70 years of age (no PPI use, n = 14 795, HR 0.62, CI 0.53 to 0.74; PPI use, n = 6088, HR 0.96, CI 0.74 to 1.24, P < 0.001 for interaction) but not in those < 70 years of age (no PPI use, n = 13 116, HR 0.60, CI 0.43 to 0.84; PPI use, n = 4089, HR 0.42, CI 0.26 to 0.69, P = 0.90 for interaction).
Concurrent use of proton-pump inhibitors, particularly at ≥ 1 dose-year, was associated with reduced effectiveness of alendronate for preventing hip fractures in older adults.
*HR = hazard ratio; other abbreviations defined in Glossary. HR < 1 indicates reduction in risk for hip fracture with use of alendronate.
†Adjusted for age, sex, comorbid conditions, past fractures, and number of comedications and based on assumption of 100% refill compliance for alendronate.
Ito K. Proton-pump inhibitors were associated with reduced effectiveness of alendronate for preventing hip fractures. Ann Intern Med. ;155:JC4–13. doi: 10.7326/0003-4819-155-8-201110180-02013
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Published: Ann Intern Med. 2011;155(8):JC4-13.
Emergency Medicine, Geriatric Medicine, Hospital Medicine.
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