Osteoarthritis. Epidemiologic and genetic aspects

Abstract: The purpose of this study was to (I) assess the association between body mass index (BMI) and total hip replacement (THR) and total knee replacement (TKR) due to osteoarthritis (OA), (II) assess the association between the mechanical load of work and THR and TKR due to OA, (III) evaluate the natural history of radiographic hip OA with regards to THR and hip fracture, (IV) to determine the prevalence of radiographic OA in patients with hip fracture, and (V) to examine and compare the inheritance patterns of THR for OA and hip fracture. OA was previously regarded as a consequence of the wear and tear the joint is subjected to during one’s lifetime. At the turn of the century the genetics of OA were of high interest. In recent years there has been renewed interest in the effects of mechanical load on the joint. In Paper I it was found that there was a strong association between being overweight (BMI 25.0–29.9 kg/m2) and the risk for TKR for both genders. This was even stronger for obese individuals (BMI 30.0 kg/m2 or above). This association was weaker for THR and this is in agreement with another recently published study that showed that the effect of BMI is less in THR than TKR. There are probably several factors that influence the effect of body weight on the risk for OA. For example malalignment has an additive effect of body weight on the development of knee OA. The effect may to an extent be purely mechanical, i.e. the increased weight putting more strain on the joint, but it has also been shown that cytokines originating from adipose tissue have an effect on cartilage metabolism. In Paper II the association between profession and total joint replacement in the knee and hip was explored. It was found that male farmers have greatly increased odds for total joint replacement, in both hip and knee, compared to other professions. It is not clear why farming has much greater odds for joint replacement due to OA than other physical labour professions. Farming was also the profession that showed the greatest degree of inheritance, so it is possible that it has a interacting effect. One possibility is that farmers, being raised on a farm, are exposed to heavy physical labour at a young age and it has been hypothesised that this can be detrimental for the joints. In epidemiologic studies, definition of OA can be based on a set of questions, purely radiographic grading or a clinical definition, which may be presence of a TJR or a combination of radiographic changes and clinical symptoms and signs. Previous studies have shown discrepancies between these definitions. In Paper III a cohort of subjects that had undergone a colon radiography were followed for 11-28 years. Their radiographic hip status was registered at baseline. The most striking finding was that after 11-28 years, only 17% of those with radiographic OA at baseline had undergone THR. The individuals with radiographic hip OA that were subject to a hip fracture were so few, that no strong conclusions could be drawn based on that group. In a publication four decades ago it was claimed that there was an inverse relationship between hip OA and hip fracture. Since then there have been publications both supporting and refuting this claim. In Paper IV the prevalence of radiographic hip OA in a cohort of patients with hip fracture was examined. The odds for having radiographic hip OA were one third in patients with hip fracture, compared to controls. The prevalence of risk factors for secondary osteoporosis was further examined and revealed that patients with hip OA and hip fracture were three times more likely to have a risk factor for secondary osteoporosis than patients with hip fracture, but without hip OA. This suggests that secondary osteoporosis needs to be accounted for and adjusted for when studying the relationship between OA and osteoporosis. Based on these findings we hypothesised that this inverse relationship between hip OA and hip fracture might be explained by inheritance. The theory was that both THR and hip fracture run in the family, but in distinctly separate families. Previous publications have shown that patients with THR are more related to each other than the population in general. Paper V therefore examined if patients with THR were less related to patients with hip fracture than can be expected in the population. This hypothesis was found to be false. It was revealed that patients with hip fracture were more related to other patients with hip fracture, as expected, but the apparent inverse relationship between hip OA and hip fracture could not be explained by inheritance.