Identifying Structural Change in Response to Vitamin D Therapy in Knee Osteoarthritis

Abstract

Background: Knee osteoarthritis (OA) is a disease affecting the whole joint including cartilage, bone and soft tissues. These structures can be assessed quantitatively using magnetic resonance imaging (MRI) though assessment is time consuming. Quantitative MRI assessment holds promise as a reliable method of determining treatment response in clinical trials. The main aim of the thesis was to determine whether vitamin D therapy, compared to placebo, is linked with a reduction in synovial tissue volume (STV) and subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA. The objectives were; 1) to apply a semi-automated approach to the assessment of STV on MRI and to examine performance compared with manual segmentation and 2) to assess the relationship between MRI structural outcomes including STV and BML types and symptoms in men and women with symptomatic knee OA. Methods: Objective 1: 32 sagittal T1-weighted (T1-w) fat suppressed (FS) contrast enhanced (CE) MRI scans, acquired from a clinical study of brace therapy in symptomatic knee OA (BRACE), were segmented for STV using manual segmentation and a semi-automated approach based on the application of a 3D mask developed using active appearance modelling (AAM). Aim and objective 2: Data were acquired on a subsample of participants recruited to a multicentre randomised double-blind placebo-controlled trial of vitamin D therapy in men and women with symptomatic knee OA (UK VIDEO). A subsample of participants had MRI performed at yearly intervals from baseline at one study site and completed the WOMAC questionnaire. In those with serial images including a baseline scan (N = 50), STV was segmented on sagittal T1-w FS CE scans using a semi-automated approach whilst BML volume was segmented manually. BMLs were segmented by location (subchondral / ligament-based) and by the presence/absence of a cyst-like component. Results: There was no significant difference in STV measured using the semi-automated approach compared to manual segmentation (mean difference: 207.2 mm3, 95% CI -895.2 to 1309.7) though the approach was quicker (18 vs. 71 minutes). Reliability was very good. Using data from UK VIDEO, an increase in knee pain was associated with an increase in STV (b = 2.2, 95% CI 0.6 to 3.7), the volume of subchondral BMLs with cyst-like components (b = 1.3, 95% CI 0.1 to 2.4) and the volume of the cyst-like component itself (b = 0.06, 95% CI 0.02 to 0.1). There was no significant difference at 2 years between the vitamin D and placebo groups in mean change from baseline for STV (b = 93.9 mm3, 95% CI -1605.0 to 1792.7) and subchondral BML volume (b = -313.5 mm3, 95% CI -4244.7 to 3617.7). Conclusions: A semi-automated approach to the assessment of STV is reliable and is more time efficient than manual segmentation. STV assessed using this approach and also subchondral BMLs with cyst-like components were associated with increasing knee pain. Vitamin D supplementation for 2 years had no significant effect on change in subchondral BML volume or STV in men and women with symptomatic knee OA.

Date of Award	1 Aug 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Terence O'Neill (Supervisor), David Felson (Supervisor) & Richard Hodgson (Supervisor)