Introduction & Objectives
Osteoarthritis (OA) is the most common form of arthritis in developed countries, representing an increasing health economic burden.1 Patients with knee or hip OA have excess all-cause mortality compared with the general population, and there is no curative treatment for OA.2
Besides age and sex, modifiable factors have been shown to be associated with the risk for OA, the highest level of evidence being for obesity and joint injury.3,4 Obesity is a major risk factor for OA incidence and progression at the knee, and to a lesser extent, at the hip.5 In addition, the role of obesity is strongly supported by findings of improvement of knee symptoms in patients undergoing weight loss.6,7 Body mass index (BMI) and other factors are associated with prevalence, incidence or progression of OA. High bone mineral density (BMD) is associated with an increased risk of radiographic hip OA or knee OA and with total joint replacement.8-10 Results from prospective studies of incident radiographic OA or OA progression are controversial.11
The concept of a “metabolic OA” phenotype was recently proposed.4 However, because metabolic factors are closely related to BMI, their BMI-independent contribution to the risk of OA is unknown. Previous studies have shown that the presence of the metabolic syndrome and many of its components are associated with the risk of hand and knee OA.12-14 Most associations with each of the metabolic syndrome components, however, become nonsignificant after adjustment for BMI.13,15
In addition, conflicting data regarding type 2 diabetes as a BMI-independent predictor of OA have been reported.16,17 The results from classic epidemiologic studies may be affected by residual confounding or reverse causation.
Funck-Brentano et al. hypothesized that causal associations may differ by OA site, and they undertook this study to identify causal risk factors of knee, hip and hand OA.
Individual-level data from 384,838 unrelated participants in the UK Biobank study were analyzed. Mendelian randomization analyses were performed to test for causality for BMI, BMD, serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels, type 2 diabetes, systolic blood pressure (BP) and C-reactive protein (CRP) levels. The primary outcome measure was OA determined using hospital diagnoses (all sites, n=48,431; knee, n=19,727; hip, n=11,875; hand, n=2,330). Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.
Mendelian randomization analyses demonstrated a robust causal association of genetically determined BMI with all OA (OR per SD increase 1.57 [95% CI 1.44–1.71]), and with knee OA and hip OA, but not with hand OA. Increased genetically determined femoral neck BMD was causally associated with all OA (OR per SD increase 1.14 [95% CI 1.06–1.22]), knee OA, and hip OA. Low systolic BP was causally associated with all OA (OR per SD decrease 1.55 [95% CI 1.29– 1.87]), knee OA, and hip OA. There was no evidence of causality for the other tested metabolic factors or CRP level.
The study findings indicate that BMI exerts a major causal effect on the risk of OA at weight-bearing joints, but not at the hand. Evidence of causality of all OA, knee OA and hip OA was also observed for high femoral neck BMD and low systolic BP. However, the researchers found no evidence of causality for other metabolic factors or CRP level.
Refer to the full article for all source material.
Excerpted and adapted from:
Funck-Brentano T, Nethander M, Movérare-Skrtic S, et al. Causal factors for knee, hip, and hand osteoarthritis: A Mendelian randomization study in the UK biobank. Arthritis Rheumatol. 2019 Oct;71(10).