Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees

Xu, Lei1,3,4; Hu, Yizhong Jenny2; Peng, Ying2; Wang, Zexi2; Wang, Jingyi2; Lu, W. William3; Tang, Bin1; Guo, X. Edward2,5

2023-02-01

10.1016/j.bone.2022.116638

BONE   Impact Factor & Quartile

8756-3282

1873-2763

Anterior cruciate ligament (ACL) tear leads to post-traumatic osteoarthritis (PTOA), a significant clinical burden worldwide that currently has no cure. Recent studies suggest a role of subchondral bone adaptations in the development of PTOA. Particularly, microstructural changes in the rod-and-plate microstructure of subchondral bone may precede and contribute to OA progression. In this study, we quantified microstructural changes in subchondral trabecular rods and plates after ACL-transection for the first time in the well-established preclinical canine model of PTOA and investigated the therapeutic potentials of a bisphosphonate (zoledronate) and NSAID treatment (meloxicam). Unilateral hindlimb ACL transection was performed on skeletally-mature (2-year-old, N = 20) and juvenile (10-month-old, N = 20) male beagles. Animals were assigned to 4 groups (N = 5): ACLT, un-operated control, ACLT with zoledronate, and ACLT with meloxicam treatment. Subchondral bone microstruc-ture was evaluated by micro-computed tomography and cartilage integrity was evaluated histologically. We found that ACL-induced subchondral bone changes depended on skeletal maturity of animals. In mature animals, significant loss of trabecular plates that resulted in reduced PR ratio occurred at Month 1 and persisted until Month 8. Zoledronate treatment prevented trabecular plate loss while meloxicam treatment did not. Whether cartilage degeneration is also attenuated warrants further investigation. In juvenile animals that have not reached skeletal maturity, transient changes in trabecular plate and rod microstructure occurred at Month 3 but not Month 9. Neither zoledronate nor meloxicam treatment attenuated bone microstructural changes or cartilage damages. Findings from this study suggest that early inhibition of bone resorption by bisphosphonate after injury may be a promising therapeutic approach to prevent alterations in subchondral bone microstructure associated with PTOA. Our results further demonstrate that pathogenesis of PTOA may differ between adolescent and adult patients and therefore require distinct management strategies.

Post-traumatic osteoarthritis Subchondral bone Bone microstructure ACL-transection Bisphosphonate NSAID

SCI

English

First

[202201020476]

Endocrinology & Metabolism

Endocrinology & Metabolism

WOS:000899593700009

ELSEVIER SCIENCE INC

CLINICAL MEDICINE

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen, Peoples R China
2.Columbia Univ, Dept Biomed Engn, Bone Bioengn Lab, New York, NY USA
3.Univ Hong Kong, LKS Fac Med, Dept Orthopead & Traumatol, Hong Kong, Peoples R China
4.Guangdong Second Prov Gen Hosp, Dept Orthopead & Traumatol, Guangzhou, Guangdong, Peoples R China
5.Columbia Univ, Dept Biomed Engn, 351 Engn Terrace,Mail Code 8904,1210 Amsterdam Ave, New York, NY 10027 USA

Xu, Lei,Hu, Yizhong Jenny,Peng, Ying,et al. Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees[J]. BONE,2023,167.

Xu, Lei.,Hu, Yizhong Jenny.,Peng, Ying.,Wang, Zexi.,Wang, Jingyi.,...&Guo, X. Edward.(2023).Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees.BONE,167.

Xu, Lei,et al."Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees".BONE 167(2023).