Alendronate Inhibits Spine Fusion in a Rat Model

Introduction: Osteoporosis and degenerative spine conditions frequently coexist in the elderly patient. Because alendronate is the most commonly prescribed antiresorptive agent, many elderly patients who present for spine fusion will be taking alendronate. It is therefore essential to understand the effects of alendronate on spinal fusion. Previous studies have demonstrated histologic changes in fusion masses after alendronate treatment, but none have shown significant changes in fusion rates assessed by manual palpation, the gold standard in fusion assessment. The purpose of this study is to investigate the effects of alendronate on posterolateral spine fusion in a rat model.

Methods: Seventy-five Sprague-Dawley rats underwent posterolateral intertransverse fusion at L4-5 using tailbone autograft. Animals were divided into control (saline), low (5mcg/kg/day), and high dose alendronate (50mcg/kg/day) groups. Allometric scaling calculations determined that 5mcg/kg/day in rats is equivalent to the dose used clinically in humans. Medication was delivered by subcutaneous osmotic pump and animals were sacrificed at 8 weeks. Spine specimens were dissected free of soft tissue. Fusion was defined as absence of motion at L4-5 upon manual palpation. Histomorphometry of fusion masses was performed to determine percent area occupied by bone and marrow elements. Fusion mass area on radiographs was calculated using Bioquant Imaging System.

Results: The fusion rate by manual palpation was 95% in controls, 50% in the low alendronate group, and 40% in the high alendronate group. Significant differences were observed between the control and alendronate groups (p<0 .002), but no significant difference was seen between the two alendronate groups (p="0.57)." Histomorphometry of fusion masses demonstrated statistically and dose dependent decreases in marrow element area with increasing (16%, 8%, 6% respectively, p<0.001) corresponding increases bone (43%, 52%, 55% p<0.001). Radiographic mass 86- 111% higher compared to controls (p<0.001)

Conclusions: This is the first study to demonstrate that alendronate inhibits spine fusion when assessed by manual palpation. Higher percentages of bone area in fusion masses in alendronate-treated animals did not correlate with fusion and likely resulted from unincorporated bone graft. Increased marrow elements in animals not treated with alendronate probably represent new bone formation and remodeling. Alendronate’s beneficial effect in osteoporosis is primarily exerted by osteoclast inhibition but in spine fusion the incorporation and remodeling processes, mediated by osteoclasts and osteoblasts, are disrupted. Osteoblast inhibition may result from direct pharmacologic effects or from disruption of osteoblast-osteoclast paracrine signaling. Based on these data, we recommend that patients undergoing fusion should not take alendronate.