Compartment-specific associations between knee joint space width and clinical outcomes

Abstract Introduction Joint space width (JSW) is an established radiographic component of knee osteoarthritis (OA), but the relative importance of medial and lateral compartment-specific JSW remains unclear. This study aimed to investigate compartment-specific minimum JSW (mJSW) and its associations with knee OA clinical outcomes, inflammatory arthritis, and knee alignment. Methods This study included 53,609 UK Biobank participants with bilateral knee dual-energy X-ray absorptiometry (DXA) imaging. Machine-learning algorithms derived medial and lateral compartment mJSW, with whole-joint mJSW defined as the smaller of the two compartments. Knee alignment was derived from paired whole-body DXA scans. Associations with knee pain, hospital-diagnosed knee OA, autoimmune and crystal inflammatory arthritis, knee alignment, and total knee replacement (TKR) were examined using regression models which accounted for individuals with bilateral knee imaging. Sex-stratified and mediation analyses were also performed. Results Mean medial and lateral compartment mJSW were 3.9 ± 0.7 and 4.1 ± 0.9 mm, respectively, with smaller values in women than men. Approximately 60% of whole-joint mJSW originated from the medial compartment. Narrower medial compartment mJSW was associated with knee pain (OR per SD decrease: 1.15 [95% CI 1.12, 1.18]), hospital-diagnosed knee OA (OR 1.29 [1.23, 1.35]), and TKR (HR 1.73 [1.58, 1.89]), with progressively stronger associations across these outcomes. Whole-joint mJSW showed similar associations but lateral compartment mJSW showed little evidence of associations with OA clinical outcomes. Medial compartment mJSW showed associations with rheumatoid arthritis (OR 1.25 [1.15, 1.37]) and psoriatic arthritis (OR 1.29 [1.09, 1.52]), whilst lateral compartment mJSW did not. Narrower medial and lateral compartment mJSW were associated with varus and valgus alignment, respectively. Varus alignment mediated 16.8% (95% CI 0.13, 0.20), 12.7% (0.10, 0.16), and 6.9% (0.05, 0.08) of the associations between medial compartment mJSW and knee pain, knee OA, and TKR, respectively. Conclusions Medial compartment mJSW was the compartment-specific measure most strongly associated with knee OA clinical outcomes. These relationships were only partly explained by varus alignment. There was no change in pattern of associations between inflammatory and OA clinical outcomes. Medial compartment mJSW seems to provide the most informative quantitative marker for large-scale population and genetically informed studies of knee OA.