Background/Purpose: Joint pain is common in older adults; typically multiple joints are involved.  Obesity is an important risk factor in pathogenesis of multi-site joint pain (MSJP). Potential mechanisms include increased physical loading and systemic inflammation, but may also include genetic factors. However, whether the effects of fat mass on pain are related to loading or to systemic inflammation is unclear. There may also be other underlying mechanisms involved in the association between obesity and pain. Therefore, this study aimed to determine longitudinal associations between fat mass and MSJP; and to determine genetic correlation between heritability of body mass index (BMI) and knee pain. 

Methods: Longitudinal population-based Tasmanian Older Adult Cohort study of older adults (n=1099). Presence of pain (yes/no) at the neck, back, hands, shoulders, hips, knees and feet was assessed by questionnaire at baseline and after 2.6 and 5.1 years. Fat mass was assessed at baseline using dual energy x-ray absorptiometry. Longitudinal data was analysed using mixed effect models, adjusting for age, sex, physical activity, educational and occupational status, and quality of life. 748 samples typed on the exome chip yielded 266,163 single nucleotide polymorphisms (SNPs). The genetic correlation between BMI and knee pain measured by WOMAC was estimated using genome-wide complex trait analysis software.

Results: Study participants were older adults (average age 63 years; range 51 to 81 years). 58% of participants reported pain at >2 sites. Participants reporting greater number of painful sites had higher baseline fat mass and BMI. Greater fat mass was associated with greater odds of MSJP (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.002, 1.011), pain in lower limbs (knee, hip and feet) (OR= 1.042 to 1.077, all P≤0.002), and hand pain (OR 1.027; 95% CI 1.000 to 1.055), after adjustment for confounders. Results were similar with BMI as the outcome. Estimates of heritability (h2) accounted for by the SNPs were 83% for BMI and 72% for knee pain. The genetic correlation between BMI and knee pain was 8% independent of age, sex and principal components (P=0.003).

Conclusion: High fat mass and high BMI independently predict MSJP, lower limb pain and hand pain, suggesting that systemic inflammatory factors are more important than loading in the pathogenesis of pain at multiple sites. Genetic correlation between BMI and knee pain support the importance of genetic factors in pain pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/which-factors-explain-multi-site-pain-caused-by-obesity-a-5-year-follow-up-study-in-older-adults/