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Alendronate Inhibits Spine Fusion in a Rat Model

Huang, Russel C., MD*; Khan, Safdar N., MD*; Sandhu, Harvinder S., MD*; Metzl, Joshua A., BS; Cammisa, Frank P. Jr, MD*; Zheng, Fengyu, MD*; Sama, Andrew A., MD*; Lane, Joseph M., MD*

doi: 10.1097/01.brs.0000186470.28070.7b
Basic Science

Study Design. A posterolateral lumbar fusion model in rats.

Objective. To study the effects of alendronate on posterolateral lumbar fusion in rats.

Summary of Background Data. To our knowledge, there are no studies that show a significant inhibition of manual palpation-assessed spine fusion by alendronate.

Methods. A total of 75 Sprague-Dawley rats underwent intertransverse fusion with 7-tailbone autograft at L4–L5. Animals received saline (control), alendronate equivalent to human dose (dose1, 5 μg/kg/day), or 10 times the human dose (dose10, 50 μg/kg/day) via subcutaneous osmotic pumps starting the day of surgery. Eight weeks after surgery, animals were euthanized, and fusion was assessed by manual palpation. Radiographic area and optical density of fusion masses were calculated. Histomorphometry was used to assess the percentage area of fusion masses occupied by bone or marrow tissues.

Results. Manual palpation fusion rates were lower in alendronate groups (50% and 40%, respectively) than in the control group (95%, P = 0.002). Interobserver and intraobserver kappa values were high (0.97−1.00). There were dose-dependent and statistically significant (P < 0.001) increases in fusion mass area and optical density with increasing alendronate dose. Fusion masses in dose10 animals had significantly higher percent area of bone tissue (P = 0.01) and lower percent area of marrow elements (P < 0.001) when compared to control animals.

Conclusions. Alendronate inhibits spine fusion in rats. Fusion masses in alendronate-treated animals appeared radiographically larger and denser than those in control animals despite lower fusion rates. Quantitative histomorphometry confirmed that alendronate inhibited bone graft resorption and incorporation. We recommend that patients undergoing spine arthrodesis should not take alendronate until fusion is achieved.

Alendronate significantly inhibited posterolateral lumbar fusion in a rat model as assessed by manual palpation. Histomorphometry and radiographs showed altered bone graft resorption and incorporation. Patients undergoing spine fusion should not take alendronate.

From the *Hospital for Special Surgery, New York, New York, and †University of Missouri-Columbia, Columbia, Missouri.

Acknowledgment date: September 1, 2004. First revision date: November 30, 2004. Acceptance date: December 1, 2004.

Both Drs. Huang and Khan contributed equally to this work.

This work was funded by the 2002 Orthopaedic Research and Education Foundation Katherine W. Walker Resident Research Grant.

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

Foundation funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Russel C. Huang, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021; E-mail:

© 2005 Lippincott Williams & Wilkins, Inc.