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The Association of Anticonvulsant Use with Fractures in Spinal Cord Injury

Carbone, Laura MD, MS; Chin, Amy S. MS; Lee, Todd A. PhD; Burns, Stephen P. MD; Svircev, Jelena N. MD; Hoenig, Helen MD, MPH; Akhigbe, Titilola MD; Thomas, Fridtjof PhD; Bailey, Lauren MS; Weaver, Frances PhD

American Journal of Physical Medicine & Rehabilitation: December 2013 - Volume 92 - Issue 12 - p 1037–1050
doi: 10.1097/PHM.0000000000000014
CME Article . 2013 Series . Number 9

Objective The aim of this study was to determine whether anticonvulsants, including the benzodiazepine subclass, are associated with an increased risk for lower extremity fractures in male patients with spinal cord injury.

Design All male patients with a history of a traumatic spinal cord injury of 2 yrs’ duration or longer in the Veterans Affairs Spinal Cord Disease Registry from 2002 to 2007 were included. Incident lower extremity fractures during this period and anticonvulsant use were identified. The association of anticonvulsant use, overall, by type (enzyme inducing, non–enzyme inducing), by number (monotherapy vs. polytherapy), by benzodiazepine subclass, and by individual medication used was determined.

Results In this cohort, 892 veterans sustained a fracture, and 6555 did not. Compared with nonusers of anticonvulsants, there was a significant positive relationship with fractures by overall use of anticonvulsants (HR, 1.17 [95% CI, 1.01–1.36]), by users of the benzodiazepine subclass (HR, 1.28 [95% CI, 1.11–1.47]), and by polytherapy compared with monotherapy (HR, 1.20 [95% CI, 1.00–1.42]) but not by anticonvulsant type (HR, 0.92 [95% CI, 0.58–1.47]). Temazepam (HR, 1.28 [95% CI, 1.01–1.62]), alprazolam (HR, 1.54 [95% CI, 1.04–2.29]), and diazepam (HR, 1.23 [95% CI, 1.06–1.41]) were significantly positively associated with fractures.

Conclusions Attention to fracture prevention is important when anticonvulsants are prescribed in spinal cord injury, particularly when more than one anticonvulsant is used.

From the Department of Veterans Affairs Medical Center, Memphis, Tennessee (LC, TA); Department of Medicine, University of Tennessee Health Science Center, Memphis (LC, TA); Edward J. Hines, Jr. VA Hospital, Hines, Illinois (ASC, TAL, LB, FW); University of Illinois at Chicago (TAL); VA Puget Sound Health Care System, Seattle, Washington (SPB, JNS); Department of Rehabilitation Medicine, University of Washington, Seattle (SPB, JNS); Durham VAMC, North Carolina (HH); Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis (FT); and Stritch School of Medicine, Loyola University, Maywood, Illinois (FW).

All correspondence and requests for reprints should be addressed to: Laura Carbone, MD, MS, Department of Medicine, Georgia Regents University, Section of Rheumatology, 1120 15th St, BI 5086, Augusta, GA 30912.

CME Objectives: Upon completion of this article, the reader should be able to: (1) Understand the relationship between anticonvulsant use and lower extremity fracture incidence in men with spinal cord injury (SCI), (2) Describe risk factors of lower extremity fractures in men with SCI, and (3) Explain potential mechanisms of action of anticonvulsants on lower extremity fracture risk in men with SCI.

Level: Advanced

Accreditation: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development IIR 08-033.

Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

© 2013 by Lippincott Williams & Wilkins