Purpose: The association between higher body mass index (BMI) and the presence of multi-joint pain has been well documented in the literature. Both higher BMI and multi-joint pain are common in people with knee osteoarthritis (OA) and both are associated with greater pain severity. Despite the ongoing opioid epidemic, opioid prescription is often predicated on patient reports of greater pain severity in people suffering from joint pain. Recently, greater BMI has been associated with opioid use in people with musculoskeletal pain; however, multiple pain sites and depressive symptoms were not accounted for. Therefore, in people with or at risk of knee OA, we assessed the relation of BMI to opioid use and quantified the extent to which that association may be mediated by the number of painful joint sites or depressive symptoms.
Methods: Data from the 60-month visit of the Multicenter Osteoarthritis (MOST) Study, a NIH-funded longitudinal prospective cohort of 3026 older adults with or at risk of knee OA was used. BMI was categorized as > 30 vs. < 30 kg/m2. Participants completed a body homunculus indicating the presence of painful joints in the body, which was summed. Depressive symptoms were defined by the Center for Epidemiologic Studies Depression Scale (CES-D) score. The outcome was opioid use (Yes/No) based upon participants’ reported medications. Potential confounders included age, sex, race, and Charlson comorbidity index. We quantified the indirect (i.e., mediated) effect of BMI on opioid use through the number of painful joint sites or depressive symptoms, as well as the direct effect of BMI on opioid use independent of (i.e., not mediated by) these specific causal pathways in two separate natural effects models. We additionally assessed whether the indirect effects of BMI on opioid use were different between men and women.
Results: There were 2768 eligible subjects (mean age: 68; mean BMI 31 kg/m2; 62% women). The percentage using opioids was greater in those with BMI > 30 than those whose BMI was <30, particularly with greater number of painful joints (table). In evaluating the natural indirect effect of BMI on opioid use (i.e., effect mediated by the number of painful joints or depressive symptoms), persons with BMI ≥30 had 15% higher (odds ratio [OR] = 1.15, 95% bootstrap confidence interval [CI]: 1.07, 1.24) and 9% higher (OR = 1.09, 95% CI: 1.03, 1.17), respectively, odds of opioid use than those with BMI <30 that was mediated by the number of painful joint sites and depressive symptoms, respectively. Overall, for the total effect of BMI on opioid use (i.e., that includes both indirect and direct effects), BMI ≥30 was associated with 44% higher odds of opioid use than those with BMI <30 (OR = 1.44, 95% CI: 1.08, 1.90). Sex-stratified mediation analysis resulted in similar effect sizes for the indirect effects of BMI on opioid use that were mediated by the number of painful joint sites or depressive symptoms; however, the total effect of BMI on opioid use was somewhat higher in men (OR = 1.48, 95% CI: 1.06, 2.05) than in women (OR = 1.35, 95% CI: 0.79, 2.25).
Conclusions: The number of painful joints and depressive symptoms partially explain the higher proportion of opioid use among obese persons. Greater BMI in men had a stronger association with opioid use than it did in women, independent of the number of painful joints or depressive symptoms, which is contrary to previous general reports of opioid use by sex.
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