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ItemFemale Reproductive and Hormonal Factors and Incidence of Primary Total Knee Arthroplasty Due to Osteoarthritis(WILEY, 2018-07)OBJECTIVE: To examine the associations of female reproductive and hormonal factors with incidence of total knee arthroplasty (TKA) for osteoarthritis (OA), and to determine whether the associations differ according to overweight/obesity status. METHODS: This study included 22,289 women in the Melbourne Collaborative Cohort Study. Data on age at menarche, pregnancy, parity, years of menstruation, oral contraceptive (OC) use, menopausal status, and hormone replacement therapy (HRT) were collected in 1990-1994. Incidence of TKA during 2001-2013 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. All analyses were adjusted for age, body mass index (BMI) at midlife, change in BMI (from early reproductive age to midlife), country of birth, physical activity, smoking, and education level. RESULTS: Over the course of 12.7 years, 1,208 TKAs for OA were identified. Ever being pregnant was associated with increased risk of TKA (hazard ratio [HR] 1.32 [95% confidence interval (95% CI) 1.06-1.63]). Parity was positively associated with risk of TKA (P for trend = 0.003). OC users had increased risk of TKA compared with non-users (for OC use of <5 years, HR 1.25 [95% CI 1.08-1.45]; for OC use of ≥5 years, HR 1.17 [95% CI 1.00-1.37]). A 1-year increase in menstruation was associated with a 1% decrease in risk of TKA (HR 0.99 [95% CI 0.97-0.99]). These associations remained significant only in women of normal weight at early reproductive age. Current HRT users had increased risk of TKA compared with non-users (HR 1.37 [95% CI 1.14-1.64]); the association was significant only in non-obese women at midlife. CONCLUSION: Reproductive and hormonal factors were associated with risk of knee OA. These associations remained significant in women of normal weight at early reproductive age and in non-obese women at midlife. Further work is needed to understand the complex effect of these factors on knee OA.
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ItemAssociation between metformin use and disease progression in obese people with knee osteoarthritis: data from the Osteoarthritis Initiativea prospective cohort study(BMC, 2019-05-24)OBJECTIVE: To examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis. METHODS: This study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m2). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n = 56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n = 762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4 years. Total knee replacement over 6 years was assessed. General linear model and binary logistic regression were used for statistical analyses. RESULTS: The rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of - 0.86% per annum (95% CI - 1.58% to - 0.15%, p = 0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (odds ratio 0.30, 95% CI 0.07-1.30, p = 0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes. CONCLUSIONS: These data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.