Incidence of fractures of the femur, including subtrochanteric, up to 8 years since initiation of oral bisphosphonate therapy: a register-based cohort study using the US MarketScan claims databases
- First Online:
- 724 Downloads
In a cohort study of users of bisphosphonates, we evaluated the incidence of fragility fractures at all sites on the femur following for up to 8 years of therapy with alendronate or risedronate. We did not find evidence for a reversal of fracture protection with long-term use of bisphosphonates.
Few studies have acquired adequate data with prolonged follow-up on bisphosphonate users in the general population to evaluate their long-term effects on the risk of hip fractures including those in the subtrochanteric region.
This cohort study utilizes a large USA database (January 1, 2000 to June 30, 2009). We compared patients with higher versus lower degrees of compliance [medication possession ratio, MPR <1/3 (the reference), 1/3–<2/3, or ≥2/3]. Radiographic adjudication of fracture site and features were not performed. Hazard ratios (HR) for fracture were estimated using time-dependent Cox models. Restricted cubic splines (RCS) were used to plot HRs for fracture against duration of therapy.
There were 3,655 incident cases of femoral fracture (764 subtrochanteric/shaft, 2,769 hip) identified during 917,741 person-years of follow-up (median = 3 years) on 287,099 patients (267,374 were women) from the date when they initiated oral bisphosphonate therapy. The corresponding HRs (95% confidence interval, CI) for overall femoral fractures associated with each additional year of therapy were 0.93 (0.86–1.01) within 5 years, and 0.89 (0.77–1.03) beyond 5 years for risedronate and 0.86 (0.81–0.91) and 0.95 (0.84–1.07) for alendronate, respectively. The corresponding estimates for subtrochanteric/shaft fractures were 1.05 (0.87–1.26) and 0.89 (0.60–1.33) for risedronate and 0.99 (0.92–1.05) and 1.05 (0.92–1.20) for alendronate, respectively. The HRs (95% CI) for overall femoral fractures associated with each additional year of alendronate or risedronate therapy within 5 and beyond 5 years were not significantly different.
Our study showed persistence of overall hip fracture protection with long-term use of alendronate or risedronate.
KeywordsAtypical femur fractures Femoral shaft fractures Fragility fractures Low-energy femoral fractures Medication possession ratio Oral bisphosphonates Subtrochanteric fractures
- 1.Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321Google Scholar
- 2.Pazianas M, Cooper C, Ebetino FH, Russell RG (2010) Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis. Ther Clin Risk Manag 21(6):325–43Google Scholar
- 7.Rizzoli R, Akesson K, Bouxsein M, Kanis JA, Napoli N, Papapoulos S, Reginster JY, Cooper C (2011) Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report. Osteoporos Int 22(2):373–90, Epub 2010 Nov 18PubMedCrossRefGoogle Scholar
- 8.Adamson DM, Chang S, Hansen LG (2008) Health research data for the real world: the Marketscan databases. Thompson Healthcare, New YorkGoogle Scholar
- 13.Curtis JR, Westfall AO, Cheng H, Lyles K, Saag KG, Delzell E (2008) Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users. J Bone Miner Res 23(9):1435–41Google Scholar
- 17.Abrahamsen B, Eiken P, Eastell R (2010) Cumulative alendronate dose and the long-term absolute risk of subtrochanteric and diaphyseal femur fractures: a register-based national cohort analysis. J Clin Endocrinol Metab 95(12):5258–65, Epub 2010 Sep 15Google Scholar
- 21.Salminen ST. Femoral shaft fractures in adults: epidemiology, fracture patterns, nonunions, and fatigue fractures. Helsinki University Printing House, Helsinki 2005 ISBN 952-10-2523-9, http://www.doria.fi/bitstream/handle/10024/2183/femorals.pdf?sequence=1