The time-dependent effect of ibandronate on bone graft remodeling in an ovariectomized rat spinal arthrodesis model

In osteoporotic patients undergoing spinal arthrodesis, the use of bisphosphonates (BPs) remains controversial with regard to bone fusion. There is no consensus about the appropriate time to give BPs to patients with osteoporosis undergoing spinal arthrodesis.

We aimed to study the effect of BPs, given at different times, on the bone response to osteoporotic spinal arthrodesis.

Radiological, histologic, and molecular assessments of bone formation after the different administration time of ibandronate in an ovariectomized (OVX) rat spinal fusion model.

Female Sprague-Dawley rats (n=100) were OVX (n=80) or non-OVX operated (n=20) and randomized into five groups: non-OVX, osteoporosis, and osteoporosis with early, simultaneous, and late BP groups. Eight weeks after ovariectomy, lumbar spinal arthrodesis was performed using autologous tailbones. Animals were killed 4 and 8 weeks after arthrodesis, and bone formation was assessed by measuring bone mineral density (BMD), messenger RNA expression, manual palpation, radiological evaluation, and histomorphometry.

Compared with late administration, early administration of ibandronate increased femur BMD in OVX rats and did not hinder bone fusion. Radiological analysis showed that groups given early ibandronate had increased bone volume in the grafted site 8 weeks after surgery. Histomorphometric analysis showed that ibandronate positively affected endochondral and intramembranous ossification. In the OVX groups, ibandronate increased bone turnover to a level similar to that in the non-OVX group. These findings suggested that early administration of ibandronate did not inhibit osteogenesis, including endochondral and intramembranous ossification and fusion rate.

Our results suggest that the early administration of BPs may not hinder the bone fusion of osteoporotic patients undergoing spinal arthrodesis.