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


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


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our results suggest that the early administration of BPs may not hinder the bone fusion of osteoporotic patients undergoing spinal arthrodesis.
Department of Neurosurgery, Seoul National University Boramae Medical Center, 5 Gil 20, Boramae-Road, Dongjak-Gu, Seoul, Korea.
Sung Bae
SB
Park
Department of Radiology and the Institute for Metalbolic Disease, Wonkwang University School of Medicine, Shinyong-Dong, Iksan, Jeonbuk, Korea.
Seong Hoon
SH
Park
Department of Pathology, Inje University College of Medicine, Seoul Paik Hospital, Seoul, Korea.
Yun Kyung
YK
Kang
Department of Neurosurgery, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea. Electronic address: chunkee.chung@gmail.com.
Chun Kee
CK
Chung
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects*; D016025:Bone Transplantation / Q000379:methods*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005269:Femur / Q000187:drug effects; D000077557:Ibandronic Acid; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy / Q000601:surgery; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013123:Spinal Fusion / Q000379:methods*; D013997:Time Factors
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid
Bisphosphonate; Bone; Fusion; Ibandronates; Osteoblast; Osteoclast; Osteoporosis; Rat; Remodeling; Spine