TITLE:
Investigation of Bone Union at the Proximal Tibial Osteotomy Site in a Chronic Kidney Disease (CKD) Rat Model
AUTHORS:
Kenta Tominaga, Yuji Kasukawa, Michio Hongo, Koji Nozaka, Hiroyuki Nagasawa, Hiroyuki Tsuchie, Yuichi Ono, Manabu Watanabe, Takashi Kawaragi, Yo Morishita, Naohisa Miyakoshi
KEYWORDS:
Chronic Kidney Disease, Bone Healing, Adenine-Induced Model, Tibial Osteotomy, Cancellous Bone, Endochondral Ossification
JOURNAL NAME:
Open Journal of Orthopedics,
Vol.15 No.12,
December
31,
2025
ABSTRACT: Purpose: Chronic kidney disease (CKD) profoundly affects bone metabolism, contributing to CKD-related mineral and bone disorder and secondary osteoporosis, which increases fracture risk. Delayed bone union is also common in CKD. This study evaluated whether cancellous bone healing at proximal tibial osteotomy sites is delayed in adenine-induced CKD rats. Methods: Eight-week-old male Wistar rats were divided into two groups: CKD (fed a 0.75% adenine diet for 4 weeks to induce stage 3 CKD) and control. Proximal tibial osteotomy was performed at age 20 weeks. Bone healing was evaluated at 2 and 4 weeks post-osteotomy via micro-computed tomography (micro-CT) and histological analyses. Serum biochemistry was also assessed. Results: CKD rats exhibited significantly elevated blood urea nitrogen and creatinine, indicating renal dysfunction, whereas serum calcium and phosphate remained within normal ranges. Micro-CT analysis showed no significant differences between groups in cortical or trabecular bone parameters at the osteotomy site. However, histological evaluation revealed significantly reduced bone union and cartilage formation in CKD rats 2 weeks post-osteotomy, suggesting delayed early bone healing. By 4 weeks, no significant difference in bone union was observed between groups. Early-stage healing in cancellous bone was delayed in adenine-induced CKD rats, likely due to impaired endochondral ossification. Nevertheless, by 4 weeks post-osteotomy, bone union was comparable in CKD and control rats. Conclusion: These findings suggest that CKD, possibly through disrupted endochondral ossification, transiently delays cancellous bone healing. Further research is warranted to explore potential therapies to enhance fracture healing in CKD.