Abstract
BackgroundSymptomatic knee osteoarthritis is a highly age and sex associated complex disease. Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. Our study examined the risk and heritability of primary knee osteoarthritis leading to total knee arthroplasty and whether these differences were attributable to sex and age differences in heritability.MethodsAll twins of known zygosity from The Danish Twin Register alive in 1997 were examined in a nationwide population based follow-up study collecting information on all twins recorded in The Danish Knee Arthroplasty from 1997 to follow-up in 2010. Our main outcomes were the cumulative incidence, probandwise concordance rates, heritability, within pair correlations in monozygotic and dizygotic twin pairs and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total knee arthroplasty at follow up.Results92,748 twins were eligible for analyses and 576 twins had a record of primary knee osteoarthritis in The Danish Knee Arthroplasty Register at follow-up comprising 358 female and 218 male twin cases. The risk increased particular after the age of 50 years displaying significant sex differences in the elderly. In the sex stratified analyses a discrete genetic component was found in females, but in males no genetic component could be detected. In both genders common and unique environmental factors were highly significant. In the sex-adjusted analysis an additive genetic component of 18 % (0; 62), a shared environmental component of 61 % (25; 97) and an individual environmental component of 21 % (6; 36) accounted for the variation in liability to primary total knee arthroplasty.ConclusionThe risk of primary total knee arthroplasty increases significantly after the age of 50 years, in particular in females, displaying significant sex differences in the elderly. After sex-adjustment 82 % of the variation in liability to primary total knee arthroplasty was attributable to common and unique environmental factors; the remaining 18 % of this variation was attributable to additive genetic factors indicating a pivotal impact of environmental factors on this disease.
Highlights
Symptomatic knee osteoarthritis is a highly age and sex associated complex disease
The co-morbidity associated with symptomatic knee OA is subject to concern because in a recent study an increased all-cause and disease-specific mortality has been reported in patients with symptomatic and radiographic hip and knee OA [5]
The objectives of this study were to examine the probability and heritability of primary OA of the knee leading to total knee arthroplasty (TKA), both sex stratified and sex adjusted, in a competing risk setting by means of the cumulative incidence function (CIF), biometric modelling, the agerelated proband-wise concordance rates and cumulative heritability
Summary
Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. The co-morbidity associated with symptomatic knee OA is subject to concern because in a recent study an increased all-cause and disease-specific mortality has been reported in patients with symptomatic and radiographic hip and knee OA [5]. In a previously published sibling study including both genders listed for total knee arthroplasty (TKA), an increased risk in siblings to index cases after adjustment for sex, age, knee pain, BMI, Heberden’s nodes and meniscectomy was reported with odds ratios of 2.9 and 1.7 for tibiofemoral and patellofemoral OA, respectively [20]. The issue of OA in different joints being caused by common genetic processes or the genetic influence being joint site specific has previously been stressed as highly important for the design of future studies examining the nature of the genetic contribution to OA [18]
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