Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis

Abstract

Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (ORIVW-random effects 1.49 [1.23–1.80]) and negative causal effects of serum calcium (ORIVW-random effects 0.69 [0.57–0.83]) and LDL levels (ORIVW-random effects 0.93 [0.90–0.96]) on OA. Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA.

Assessing the causal associations of different types of statins use and knee/hip osteoarthritis: A Mendelian randomization study

“…In individuals with high BMI, the load-bearing pressure on the hip and knee joints is greater than that in normal-weight individuals, leading to increased friction between the articular cartilage and facilitating the development of knee and hip OA. Earlier studies have also demonstrated a link between elevated BMI and the progression of arthritis [ 29 , 30 , 43 ]. However, even after accounting for BMI as an intermediate variable, the effects of total statins and simvastatin on hip OA remained significant.…”

Burden of osteoarthritis in China, 1990–2019: findings from the Global Burden of Disease Study 2019

“…Osteoarthritis may seem to be inevitable with increased age [ 33 ]; it can be halted and/or postponed with the adoption of the previously mentioned lifestyle changes. These interventions are most effective if they are implemented in the early years of childhood [ 34 ]. Period effect refers to the improvement of public health intervention measures, health education policies, and treatment methods in a certain period, which will have an impact on the period effect of onset and death of osteoarthritis [ 35 ].…”

A bidirectional Mendelian randomization study investigating the relationship between genetically predicted systemic inflammatory regulators and chronic obstructive pulmonary disease

“…Second, the data used in this study were from populations of European ancestry, which does not reflect the heterogeneity among different populations. Third, as MR analysis assesses the cumulative effects of genetic variation, we cannot extrapolate the possible effects of clinical treatment [ 48 ]. In addition, there may be time-dependent effects and inflammation-environment interactions that could influence the results of our analysis.…”