Role of Thigh Muscle Changes in Knee Osteoarthritis Outcomes: Osteoarthritis Initiative Data

Abstract

Background Longitudinal data on the association of quantitative thigh muscle MRI markers with knee osteoarthritis (KOA) outcomes are scarce. These associations are of clinical importance, with potential use for thigh muscle-directed disease-modifying interventions. Purpose To measure KOA-associated longitudinal changes in MRI-derived muscle cross-sectional area (CSA) and adipose tissue and their association with downstream symptom worsening and knee replacement (KR). Materials and Methods In a secondary analysis of the Osteoarthritis Initiative multicenter prospective cohort (February 2004 through October 2015), knees of participants with available good-quality thigh MRI scans at baseline and at least one follow-up visit were included and classified as with and without KOA according to baseline radiographic Kellgren-Lawrence grade of 2 or higher and matched for confounders with use of propensity score matching. An automated deep learning model for thigh MRI two-dimensional segmentation was developed and tested. Markers of muscle CSA and intramuscular adipose tissue (intra-MAT) were measured at baseline and 2nd- and 4th-year follow-up (period 1) and compared between knees with and without KOA by using linear mixed-effect regression models. Furthermore, in knees with KOA, the association of period 1 changes in muscle markers with risk of KR (Cox proportional hazards) and symptom worsening (mixed-effect models) during the 4th to 9th year (period 2) was evaluated. Results This study included 4634 matched thighs (2317 with and 2317 without KOA) of 2344 participants (mean age, 62 years ± 9 [SD]; 1292 women). Compared with those without, knees with KOA had a decrease in quadriceps CSA (mean difference, -8.21 mm²/year; P = .004) and an increase in quadriceps intra-MAT (1.98 mm²/year; P = .007). Decreased CSA and increased intra-MAT of quadriceps during period 1 was predictive of downstream (period 2) KOA symptom worsening (Western Ontario and McMaster Universities Osteoarthritis Index total score: odds ratio, 0.24 [negative association] [P < .001] and 1.38 [P = .012], respectively). Quadriceps CSA changes were negatively associated with higher future KR risk (hazard ratio, 0.70; P < .001). Conclusion Knee osteoarthritis was associated with longitudinal MRI-derived decreased quadriceps cross-sectional area and increased intramuscular adipose tissue. These potentially modifiable risk factors were predictive of downstream symptom worsening and knee replacement. Clinical trial registration no. NCT00080171 © RSNA, 2022 Online supplemental material is available for this article.

Graphical abstract

Figure 1:

Flow diagram of thighs included in the study shows selection criteria and categorization of participants. KL = Kellgren-Lawrence, KOA = knee osteoarthritis, KR = knee replacement, PS = propensity score, R1 = reader 1, R2 = reader 2, WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 2:

Diagram shows preprocessing, deep learning model development, and segmentation of thigh images. 2-Y = 2nd-year FU, 4-Y = 4th-year FU, BL = baseline, FU = follow-up, IMT = intermuscular tissue, N4 = N4ITK, R1 = reader 1, R2 = reader 2, SCF = subcutaneous fat.

Figure 3:

Quantitative markers of thigh MRI assessed in this study. Axial noncontrast T1-weighted MRI scan of the quadriceps region at 33% distal femur length of the left thigh in a 52-year-old male participant without knee osteoarthritis. These markers were similar and stable on the 2nd- and 4th-year follow-up thigh MRI scans. CSA = cross-sectional area, IMT = intermuscular tissue, inter-MAT = intermuscular adipose tissue, intra-MAT = intramuscular adipose tissue, SCF = subcutaneous fat.

Figure 4:

Diagram shows timing of the study assessments. Period 1: Baseline visit to 4th-year follow-up visit. Period 2: 4th-year to 9th-year follow-up visit. BMI = body mass index, CSA = cross-sectional area, FU = follow-up, KL = Kellgren-Lawrence, KOA = knee osteoarthritis, KR = knee replacement, OARSI JSN OA = Osteoarthritis Research Society International joint-space narrowing grade, PASE = Physical Activity Scale for the Elderly, PS = propensity score, WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index.

Figure 5:

Main study findings. (A–B) Axial noncontrast T1-weighted MRI scans of the quadriceps region at 33% distal femur length of left thigh in a 58-year-old male participant with knee osteoarthritis (KOA). Baseline to 4th-year (period 1) follow-up thigh MRI scans show a decrease in quadriceps CSA (A) and an increase in quadriceps intra-MAT (B). During period 2 (4th to 9th year), this participant underwent left knee replacement at 7.7 years after baseline visit, as shown in a (C) posteroanterior weight-bearing fixed flexion knee radiograph, and (D) had increased KOA-related symptoms in Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, disability, and total scores. Thigh muscle changes in period 1 were predictive of KOA clinical outcomes in period 2, regardless of KOA grade at the start of period 2.