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Natural History and Risk Factors for Adjacent Vertebral Fractures in the Fracture Intervention Trial

Frankel, Bruce, MD*; Krishna, Vibhor, MD*; Vandergrift, Alex, MD*; Bauer, Douglas C., MD, MPH; Nicholas, Joyce, PhD

doi: 10.1097/BRS.0000000000000025

Study Design. Retrospective analysis of prospectively collected follow-up data for 2.9 years.

Objective. To determine the natural history of subsequent morphometric fracture rates at adjacent levels (one level above or below a previous known baseline fracture) in a large patient database.

Summary of Background Data. The long-term risk and risk factors for adjacent-level vertebral fractures in patients with osteoporosis are unknown.

Methods. The fracture intervention trial is a large randomized, placebo-controlled trial of alendronate treatment for osteoporosis. Data from both bisphosphonate-treated and bisphosphonate-naive patients (N = 1950, vertebral fracture arm) was analyzed to detect incident morphometric fracture rates.

Results. During a mean follow-up of 2.9 years, 3.4% of patients in the alendronate group and 7.4% in the placebo group experienced adjacent-level vertebral fractures. The annual rate of adjacent-level vertebral fractures was 1.2% in the alendronate group, and 2.5% in the placebo group (overall, 1.8% per year in both groups combined). As expected, the thoracolumbar region (defined as T11, T12, and L1) seemed to be the most prone to new adjacent-level fractures. Among females with baseline prevalent fractures at the thoracolumbar junction, who subsequently experienced at least one new fracture anywhere along the spine (N = 124), 40.3% had a new adjacent-level fracture in this region. Older age at randomization, lower bone mineral density, inactivity, and placebo therapy were significantly associated with the development of adjacent-level fractures in univariate analysis (P ≤ 0.05). Multivariate analysis indicated decreased odds of adjacent-level fractures with bisphosphonate therapy and higher bone mineral density, and increased odds with older age at randomization (P ≤ 0.05).

Conclusion. New vertebral fractures adjacent to prevalent fractures occurred relatively infrequently in this treatment trial of alendronate in females with osteoporosis, and were more common with older age at randomization, lower bone mineral density and placebo treatment.

Level of Evidence: 3

The rates of adjacent-level fractures in patients with osteoporosis are unknown. We report that this rate is significantly lower than what was previously reported in the literature.

*Division of Neurosurgery, Department of Neuroscience, Medical University of South Carolina, Charleston, SC

Departments of Medicine and Epidemiology & Biostatistics, University of California, San Francisco, CA; and

Division of Biostatistics and Epidemiology, Department of Medicine, Medical University of South Carolina, Charleston, SC.

Address correspondence and reprint requests to Bruce Frankel, MD, Division of Neurosurgery, Department of Neuroscience, Medical University of South Carolina, 96 Jonathan Lucus St Ste 301, CSB Charleston, SC 29425; E-mail:

Acknowledgment date: May 24, 2012. First revision date: June 8, 2013. Second revision date: July 16, 2013. Acceptance date: August 26, 2013.

The device(s)/drug(s) is/are FDA-approved or approved by corresponding national agency for this indication.

No funds were received in support of this work.

Relevant financial activities outside the submitted work: consultancy, grants, patents, royalties.

© 2013 by Lippincott Williams & Wilkins