Knee Osteoarthritis, Potential Mediators, and Risk of All-Cause Mortality: Data From the Osteoarthritis Initiative

Abstract

Objective: To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to All-cause mortality and to identify mediators in the causal pathway.

Methods: Participants from the Osteoarthritis Initiative were divided into 4 groups: 1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren/Lawrence grade ≥2] and knee pain); 2) knee pain only; 3) radiographic knee OA only; and 4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to All-cause mortality using a multivariable Cox proportional hazards model and assessed the extent to which the association was mediated by disability, physical component summary (PCS) and mental component summary (MCS) scores for quality of life (QoL), and use of oral pain-relief medications (i.e., nonsteroidal antiinflammatory drugs and opioids).

Results: Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [95% CI] 1.6-3.1) for symptomatic knee OA, 0.9 (95% CI 0.6-1.4) for knee pain only, and 2.0 (95% CI 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95% CI 1.0-1.4) and 1.2 (95% CI 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use.

Conclusion: Participants with either symptomatic or radiographic knee OA were at an increased risk of All-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

Figure 1.. A Directed Acyclic Graph to Describe the Mediation Effect between Symptomatic Knee OA and All-cause Mortality.

OA, osteoarthritis; PCS of QoL, physical component summary score of quality of life Indirect effect: effect of symptomatic knee OA on all-cause mortality through its effect on mediators (i.e., disability and PCS of QoL) Direct effect: effect of symptomatic knee OA on all-cause mortality not through its effect on mediators (i.e., disability and PCS of QoL) Total effect: sum of indirect and direct effects Confounders: confounders of association between symptomatic knee OA and all-cause mortality (i.e., age, race, sex, body mass index, education level, weekly alcohol consumption, smoking habits, history of knee injury, comorbidities, depressive symptom and widespread pain)