Abstract
BACKGROUND
High tibial Osteotomy (HTO) realigns the forces in the knee to slow the progression of osteoarthritis. This study relates the changes in knee joint biomechanics during level gait to glutamate signalling in the subchondral bone of patients pre and post HTO. Glutamate transmits mechanical signals in bone and activates glutamate receptors to influence inflammation, degeneration and nociception in arthritic joints. Thus glutamate signalling is a mechanism whereby mechanical load can directly modulate joint pathology and pain.
METHODS
3D motion analysis was used to assess level gait prior to HTO (n=5) and postoperatively (n=2). A biomechanical model of each subject was created in Visual3D (C-motion. Inc) and used for biomechanical analysis. Gene expression was analysed by RT-PCR from bone cores from anterior and posterior drill holes, subdivided according to medial or lateral proximal tibia from HTO patients (n=5).
RESULTS
Knee adduction moment is a clinical marker of medial compartment loading. Pre-operatively the mean peak adduction moment was 3.8 ± 1.8 % body weight times height (BW.h). One subject maintained a consistent peak adduction moment pre (1.8 %BW.h) and post-operatively (1.9 %BW.h) with a reduction in the second moment peak. Another subjects peak adduction moment was significantly reduced from 6.7 %BW.h pre-operatively to 1.4 %BW.h postoperatively. GAPDH, osteocalcin, EAAT-1, EAAT1ex9skip, NR2A, KA1, OPG and RANKL mRNA expression was detected in HTO bone cores. In one patient, where HTO reduced medial compartment loading, differential expression of EAAT1ex9skip and KA1 was observed in pre and post HTO bone cores.
CONCLUSION
Changes in knee adduction moments following HTO have been identified indicating altered medial compartmental loading. This is being investigated further in larger cohorts in a 5 year study. We have demonstrated that glutamate transporters and receptors are expressed in human subchondral bone and that glutamate transporter mRNA expression may vary after HTO surgery. In arthritis, glutamate concentrations in the synovial fluid are increased, activating receptors in joint tissues and nerves to influence pathology and nociception. Thus glutamatergic signals represent a direct mechanism linking mechanical loading through the joint to pathology and pain in human arthritis.
