Alendronate inhibits spine fusion in a rat model

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 mu g/kg/day), or 10 times the human dose (dose10, 50 mu g/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.