Elsevier

Bone

Volume 48, Issue 5, 1 May 2011, Pages 966-971
Bone

Atypical fractures and bisphosphonate therapy: A cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features

https://doi.org/10.1016/j.bone.2010.12.033Get rights and content

Abstract

Atypical subtrochanteric/femoral shaft (ST/FS) fractures are increasingly reported in patients on long-term treatment with bisphosphonates (BPs). We estimated the frequency of atypical fractures and their association to BP use in patients aged ≥50 years consecutively admitted to a single center with a new femoral fracture. All individual radiographs were examined and fracture site confirmed. A case–control study of patients with low-energy ST/FS fractures, age- and sex-matched with patients with hip fractures (1:2 ratio), was performed. Patients with atypical ST/FS fractures were further compared with those with ordinary ST/FS fractures. Cortical thickness (CT) was measured in radiographs of cases and controls. Ninety-six of 906 patients (10.6%) had a ST/FS fracture. Of these, 63 with low-energy fractures were individually matched with 126 controls with hip fracture. BPs were used by 9.5% of cases and by 8.7% of controls (OR, 1.10; 95% CI, 0.39–3.06) with comparable duration of therapy between groups (54 ± 35 vs. 54 ± 52 months, P = 0.53). CT was comparable between cases and controls, BP users and non-users, and was not related to treatment duration. Atypical fractures were observed in 10/63 ST/FS cases (15.9%). Compared to patients with ordinary ST/FS fractures, those with atypical fractures were using more frequently BPs (OR, 17.0; 95% CI, 2.6–113.3) and glucocorticoids (OR, 5.3; 95% CI, 0.9–28.6). Among patients with atypical fractures, CT was comparable between BP users and non-users. In conclusion, atypical femoral fractures have a low prevalence (1.1% of all femoral fractures), compared to ordinary ST/FS fractures are more frequent in bisphosphonate users, but equally occur in patients never treated with bisphosphonates.

Research highlights

► Adjudication of all radiographs of consecutive patients with femoral fractures ► 96 of 906 (10.6%) patients had subtrochanteric fractures of which 63 were low-energy ► 10 of the 63 fractures were atypical or 1.1% of all femoral fractures ► Atypical fractures were more frequent among bisphosphonate users (OR 17.0) ► Half of the patients with atypical fractures had never used bisphosphonates

Introduction

Bisphosphonates (BPs) are the mainstay of treatment of osteoporosis, used by millions due to their proven efficacy in reducing fracture risk [1], [2]. In recent years case reports and case reviews of rather unusual fractures of the femur below the lesser trochanter (subtrochanteric or femoral shaft) have been reported in patients on long-term BP therapy [3], [4]. These fractures have been characterized by a specific radiographic pattern consisting of a simple, transverse or short oblique fracture with unicortical beaking in areas of thickened cortices, and have been designated as atypical [5], [6]. The apparent increasing frequency of these fractures, albeit still low in numbers, has attracted the attention of regulatory authorities and of the public at large.

Causality between atypical fractures and BPs is debatable [7], [8], [9], [10], [11], [12], [13]. To address this issue we reviewed all radiographs and treatment data from consecutive patients with femur fractures admitted to a single center over an 11-year period with the following specific aims: 1. To estimate the frequency of atypical fractures of the femur. 2. To examine the association between atypical fractures and BPs use. 3. To examine risk factors other than BPs potentially contributing to the risk of atypical fractures.

Section snippets

Study design

We performed a retrospective analysis of all patients aged ≥ 50 years consecutively admitted to our Institution for surgical repair of a new fracture of the femur between January 1997 and December 2007. This time frame was selected because alendronate was approved in the Netherlands for the treatment of osteoporosis in 1996. All patients were identified from hospital records using ICD-9-CM discharge codes. Radiographs of all patients were reviewed and fracture site was adjudicated and

Patients

Out of 1245 patients with a new fracture of the femur identified by ICD-9-CM discharge codes, 932 were ≥50 years (Fig. 1). Radiographs were available for review in 909 and examination of these radiographs led to exclusion of another 3 patients (one with a fracture of the acetabulum, one with Paget's disease and one with metastatic breast cancer). The final cohort consisted, thus, of 906 patients (29.4% men) with a mean age of 77.9 ± 10.5 years (range 50–99 years). Adjudication of the fracture site

Discussion

The present study, with adjudication of all radiographs of consecutive patients with femur fractures, was designed to assess the prevalence of atypical fractures and their association to BP use. In our cohort, the characteristics of the patients and the distribution of femur fractures were concordant with those reported in larger epidemiological studies in which ICD discharge codes were used for the identification of the fracture site [10], [16]. Miscoding has been previously reported in up to

Acknowledgments

We thank Ms N. Leyerzapf for her help in the initial acquisition of the data.

Financial Disclosures: S. E. Papapoulos has received consulting fees and/or honoraria from Alliance for Better Bone Health, Amgen, Eli Lilly, Merck & Co, Novartis, Pfizer, Roche/GSK, and Wyeth. He is a member of the Task Force of the American Society of Bone and Mineral Research and of the Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International

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