New research suggests the number of osteoarthritic joints may be a clinical marker of cumulative musculoskeletal disease severity, rather than a measure of individual joint disease.
Osteoarthritis affecting multiple joints has been associated with an accelerated progression of frailty, with people affected in two or three joints experiencing a 40–47% faster rate of frailty progression over six years compared to those without osteoarthritis.
The findings come from an analysis of 13,757 participants aged 45-85 years in the Canadian Longitudinal Study on Aging (CLSA), which assessed frailty at baseline and at three- and six-year follow-up. Participants were classified according to whether they had physician-diagnosed OA affecting the knee, hip, or hand.
Of the cohort, 10,193 people (74%) had no OA, while 2,535 (18%) had one affected joint, 806 (6%) had two, and 223 (2%) had three. After adjusting for age, BMI, marital status, sitting time, physical activity (light-to-moderate and strenuous exercise), and sex, the rate of frailty progression differed according to OA status.
Frailty increased overall across the cohort, but progression was slowest in those without OA (β=0.237), followed by one affected joint (β=0.293), three affected joints (β=0.330), and two affected joints (β=0.348).
Sensitivity analysis combining the two- and three-joint groups found that frailty progressed significantly faster in people with multi-joint OA than in those with single-joint disease (β=0.070), translating to a 40-47% faster rate than those without OA.
The researchers said the findings are important because OA is often studied as a disease affecting an individual joint, despite frequently occurring at multiple sites.
“Upwards of 3-in-4 people with osteoarthritis suffer from the disease in more than one joint; however, the vast majority of research into osteoarthritis focuses on single joint involvement and may not be generalizable to the greater osteoarthritis population,” they wrote.
“This mismatch suggests osteoarthritis should be conceptualized as a whole-body condition rather than an isolated joint disorder. Consistent with this, many osteoarthritis risk factors, both modifiable and non-modifiable are systemic rather than joint-specific.”
The researchers noted that OA is associated with a substantial burden of comorbid disease, with previous estimates suggesting that up to 87% of people with OA have at least one other comorbidity, including cardiovascular disease, dementia, or rheumatic disease.
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They also highlighted the potential clinical importance of the number of joints affected.
“Individuals with multi-joint osteoarthritis often report greater pain, worse functional limitations, and higher healthcare utilization compared to those with single-joint involvement. Therefore, the number of osteoarthritic joints may represent a clinically meaningful marker of cumulative musculoskeletal disease severity,” they wrote.
Around 31% of people without OA experienced a clinically meaningful increase in frailty over the six years, compared with 34% of those with one affected joint, 40% of those with two affected joints, and 38% of those with three affected joints.
People with more affected joints also tended to be older and have a higher BMI, while a smaller proportion were married. Nearly 80% of participants in the three-joint group were female, compared with around 50% of those without OA.
However, there was no statistically significant three-way interaction between time, OA frequency, and sex (β=0.009, 95% CI −0.024–0.041), suggesting the trajectory did not differ significantly by sex.
The researchers also explored whether particular combinations of affected joints were associated with different trajectories.
Among people with two affected joints, knee-plus-hip OA was associated with increased frailty progression (β=0.244, 95% CI 0.050–0.438), as was knee-plus-hand (β=0.222, 95% CI 0.076–0.367).
However, the association was not statistically significant for hip-plus-hand OA (β=0.018, 95% CI −0.244–0.209).
“Although these subgroup comparisons should be interpreted cautiously, the findings suggest that knee involvement may disproportionately contribute to frailty, which is particularly problematic because it makes up approximately 80% of osteoarthritis cases,” the researchers noted.
While the findings suggest the association between multi-joint OA and frailty extends beyond the presence of joint disease itself, the observational design means the study cannot establish that OA directly causes faster frailty progression.
“The clinical implications of this work likely relate to earlier identification of at-risk individuals and supportive, multidisciplinary management rather than disease modification,” authors concluded.
