Altered Joint Mechanics and Biological Response in Osteoarthritic Knees. (AMB-OK)

Altered Joint Mechanics and Biological Response in Osteoarthritic Knees. A Study in Patients Undergoing Corrective Treatment for Knee Misalignment.

Osteoarthritis (OA) stands out as the most prevalent joint disease. It manifests as a progressive degradation of articular cartilage, new bone growth and often synovial tissue proliferation, resulting in pain and compromised joint functionality, ultimately leading to disability. Misalignment of the lower limb (varus or valgus knees) are recognised as a risk factor for osteoarthritis onset and progression. High tibial osteotomy (HTO) is a surgical technique that allows to shift the load from the affected area to other areas with intact cartilage. Similarly to HTO, braces realign the lower limb, without the need for surgical intervention. These corrective treatments are recommended for the youngest group of patients as it allows them to stay active, as opposed to Total Knee Replacement (TKR). Until today, the effects of braces and HTO on the subchondral bone microstructure and cartilage are not well understood. Investigating these aspects to better understand treatment failures is becoming more and more crucial because global prevalence of knee OA is expected to increase with the ageing of populations.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis (OA)
• Intervention / Treatment: Diagnostic test: Photon counting CT scanning (PCCT scanning); Diagnostic test: Magnetic resonance imaging (MRI scanning); Diagnostic test: Gait analysis

Detailed Description

Osteoarthritis (OA) stands out as the most prevalent joint disease. It manifests as a progressive degradation of articular cartilage, new bone growth and often synovial tissue proliferation, resulting in pain and compromised joint functionality, ultimately leading to disability. In 83% of OA patients the knee is affected limiting people from engaging in physical activities, which paves the way for the onset of cardiovascular diseases, obesity, and diabetes. Misalignment of the lower limb (varus or valgus knees) are recognised as a risk factor for osteoarthritis onset and progression. These misalignments of the lower limbs substantially influence the load distribution across the articular surface of the knee joint, and the load imbalance causes the most loaded compartment to wear out earlier. High tibial osteotomy (HTO) is a surgical technique that allows to shift the load from the affected area to other areas with intact cartilage. Similarly to HTO, braces realign the lower limb, without the need for surgical intervention. These corrective treatments are recommended for the youngest group of patients as it allows them to stay active, as opposed to Total Knee Replacement (TKR). However, long-term survivorship of HTO ranges from 40% to 85% and evidence of long-term efficacy of braces is limited. The specific reasons for failure are not well understood, but are probably linked to improper correction, as overcorrection can lead to instability while undercorrection may fail to alleviate symptoms, and no consensus on the optimal amount exist in literature. Until today, the effects of braces and HTO on the subchondral bone microstructure and cartilage are not well understood. Investigating these aspects to better understand treatment failures is becoming more and more crucial because global prevalence of knee OA is expected to increase with the ageing of populations.

Bone remodelling occurs as a consequence of the major change in loading condition, caused by the treatments, but the time frame and the extent to which this happens is unknown. Bone quality is typically evaluated by means of dual-energy X-ray absorptiometry (DXA), which is able to detect 2D changes in bone mineral density, but not suitable to measure regional differences in bone microstructure. High resolution pheripheral quantitative CT (HR-pQCT) is a widespread imaging technique in research context. It allows for 3D measurements and it was proven that it can accurately quantify bone remodelling at the wrist. However, HR-pQCT has a low clinical applicability, due to long scanning time and small field of view, that does not allow imaging of central sites, such as the knee. Photon Counting CT (PCCT) is one of the latest advancements in CT technique, with resolution comparable to HR-pQCT but higher clinical applicability. It was shown that PCCT is suitable to detect bone turnover in the same way as HR-pQCT, allowing for direct characterization of the microstructure at the knee.

Despite extensive in vitro and in vivo research, it remains unclear how the changes in cartilage composition and structure that occur during cartilage degeneration, interact. An in silico model to investigate the causal mechanisms by which the local mechanical environment of injured cartilage drives cartilage degeneration has been developed. The model predictions showed good agreement with previous experimental observations, however a more extensive validation with in vivo data would allow to investigate more physiological conditions.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna Tarasiuk; Phone Number: +32 16 33 88 18; Email: orthopedie.research@uzleuven.be
• Study Contact Backup: Name: Harry van Lenthe, Prof. Ir.; Phone Number: +32 16 32 25 95; Email: harry.vanlenthe@kuleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen KU Leuven
      • Contact: Anna Tarasiuk; Phone Number: +32 16 33 88 18; Email: orthopedie.research@uzleuven.be
      • Contact: Harry van Lenthe, Prof. Ir.; Phone Number: +32 16 32 25 95; Email: harry.vanlenthe@kuleuven.be
      • Principal Investigator: Harry van Lenthe, Prof. Ir.
      • Sub-Investigator: Hilde Vandenneucker, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures.
• Chronic symptoms of (early) knee OA.
• Misalignment of the lower limb and scheduled for HTO surgery (regardless of the HTO technique used (lateral or medial, closing or opening wedge)) or brace treatment.
• Follow-up at UZ Leuven.

Exclusion Criteria:

• Acute OA symptoms onset (previous knee injury)
• Pregnant women
• MRI checklist incomplete or failed
• BMI > 30
• Impaired vision or neurological condition that affect coordination and balance
• Age <18 (no minors will be included in the study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High tibial osteotomy; High tibial osteotomy (HTO) is a surgical technique that allows to shift the load from the affected area to other areas with intact cartilage. This study aimes to include 10 patients receiveing HTO surgery.	Diagnostic test: Photon counting CT scanning (PCCT scanning); Photon Counting CT (PCCT) is a novel imaging technique that allows for in vivo high-resolution imaging of the bone microstructure. It has a large field of view and short scanning time compared to the current gold standard for bone microstructural quantification, High Resolution-peripheral CT (HR-pQCT). PCCT scans are performed at pre-treatment visit, 6 months, 12 months and 24 months post-treatment.; Diagnostic test: Magnetic resonance imaging (MRI scanning); Cartilage is typically imaged with MRI for its high content of water. Different MRI sequences allow to quantify anatomical aspects such as cartilage volume and thickness, but also its contents (proteoglycans and collagen). MRI scans are performed at pre-treatment visit, 12 months and 24 months post-treatment.; Diagnostic test: Gait analysis; The load shift after limb realignment will also be measured. Gait analysis (combined with musculoskeletal modelling) will be used to measure joint contact forces and knee joint geometry will be derived from the PCCT and MRI scans. Forces and geometry will be given as input to a Finite Element (FE) model of the knee joint, computing stresses and strains distribution on bone and cartilage. The gait analysis will be performed pre-treatment and 12 months post-treatment.
Experimental: Braces therapy; Braces realign the lower limb, this corrective treatments occures without the need for surgical intervention. This study aimes to include 20 patients in this treatment arm.	Diagnostic test: Photon counting CT scanning (PCCT scanning); Photon Counting CT (PCCT) is a novel imaging technique that allows for in vivo high-resolution imaging of the bone microstructure. It has a large field of view and short scanning time compared to the current gold standard for bone microstructural quantification, High Resolution-peripheral CT (HR-pQCT). PCCT scans are performed at pre-treatment visit, 6 months, 12 months and 24 months post-treatment.; Diagnostic test: Magnetic resonance imaging (MRI scanning); Cartilage is typically imaged with MRI for its high content of water. Different MRI sequences allow to quantify anatomical aspects such as cartilage volume and thickness, but also its contents (proteoglycans and collagen). MRI scans are performed at pre-treatment visit, 12 months and 24 months post-treatment.; Diagnostic test: Gait analysis; The load shift after limb realignment will also be measured. Gait analysis (combined with musculoskeletal modelling) will be used to measure joint contact forces and knee joint geometry will be derived from the PCCT and MRI scans. Forces and geometry will be given as input to a Finite Element (FE) model of the knee joint, computing stresses and strains distribution on bone and cartilage. The gait analysis will be performed pre-treatment and 12 months post-treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone microstructure quantification	Trabecular morphology will be described with the bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N).	From enrollment to the end of study at 24 months
Mechanical properties in osteoarthritic knees	A PCCT-based finite element (FE) model will be built to estimate bone strength, stiffness and apparent modulus by simulating an axial compression.	From enrollment to the end of study at 24 months
Load shift quantification	An FE model, simulating forces acting in the knee joint during physiological walking will be built, deriving such forces from gait analysis.	From enrollment to the end of study at 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteoglycans quantification	As content of cartilage, proteoglycans will be quantified using a specific MRI sequence at pre-treatment and 12 and 24 months post-treatment. These measurements will be compared with the in silico models prediction through an agreement analysis.	From enrollment to the end of study at 24 months
Collagen quantification	As content of cartilage, collagen will be quantified using a specific MRI sequence at pre-treatment and 12 and 24 months post-treatment. These measurements will be compared with the in silico models prediction through an agreement analysis.	From enrollment to the end of study at 24 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Harry van Lenthe, Prof. Ir., Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Diagnostic Techniques and Procedures; Diagnosis; Population Characteristics; Tomography; Diagnostic Imaging; Physical Examination; Health; Physical Fitness; Gait; Physical Functional Performance; Magnetic Resonance Imaging; Gait Analysis
• Other Study ID Numbers: S70583

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No