How obesity links with osteoarthritis: mechanic or metabolic?

Introduction Osteoarthritis (OA) is a highly prevalent joint disease. Obesity is one of the most important risk factors of new-onset OA and deterioration of OA. Obesity was once considered to cause OA simply by added mechanical force. Yet, more recent studies have shown that metabolic factors produced by fat tissue can also initiate inflammatory cascade that consequently can lead to OA. This is a narrative review of recent literature about how obesity leads to OA. Mechanical loading, metabolic factors and other related issues are discussed. Knowledge on how obesity links with OA will help to identify targets for modifying the metabolic effect for treatment of OA. Conclusion Excess of fat plays a role in OA by adding mechanical and metabolic loads. The factor that is more predominant depends on the joint. Introduction Osteoarthritis (OA) is the most common joint disease1 and one of the leading causes of disability2. It was once considered as a simple degenerative disease, but now is viewed as a disease of the whole joint with the involvement of cartilage, subchondral bone and synovium3. Being overweight is an important risk factor of OA4. Research on OA and obesity is of interest because obesity is a factor that can be modified. Having more knowledge on how obesity is involved in pathophysiology of OA will consequently lead to better measures to prevent the occurrence and the progression of OA. Nowadays, it is assumed that obesity plays a role in OA through two possible mechanisms. First, due to extra mechanical forces in weight-bearing joints (i.e. knees and hips) and second due to excess of metabolic factor (i.e. adipokines) secreted by fat tissues. The purpose of this article was to perform a narrative review of the literature on how obesity links with OA. Discussion The author has referenced some of its own studies in this review. These referenced studies have been conducted in accordance with the Declaration of Helsinki (1964), and the protocols of these studies have been approved by the relevant ethics committees related to the institution in which they were performed. All human subjects, in these referenced studies, gave informed consent to participate in these studies. Mechanical force Knee and hip joints endure mechanical force during activities such as walking and jogging. Several studies have investigated the measurement of the force that knee joints endure during several activities as summarized by d’Lima and co-workers5. A force of three and four times that of the body weight is transmitted across the knee joint during walking and jogging, respectively. When a subject has an excess of body weight, larger forces are exerted on the weight-bearing joints, which can lead to higher risk of having the deterioration of cartilage in OA. Interestingly, while obesity is consistently shown to be associated with new-onset OA6,7, its association with the worsening of OA is inconsistent6,8,9. The inconsistency can be explained by the difference of study population used in the studies and due to limitation in epidemiology studies10. When a large majority of study population has obesity, for example, it will limit the contrast between patient’s obesity and patients with normal weight. One of the most significant limitations of a prospective cohort study is a patient’s loss to follow-up10. Arguably, patients that are overweight are prone to loss of follow-up due to other health problems related to obesity, and precisely in these subjects the effect of obesity on OA is expected. Another possible limitation of prospective studies is the possible bias that can be introduced by how the progression is measured10. Progression of OA is often measured using a scoring system with a maximal score. In the scoring system with maximal score, a progression cannot be scored higher than the maximum. However, progression can be mild and it does not reach maximal score. When patients with maximal and mild progression are lumped together in the statistical analysis, it can lead to the dilution of the effect. Another mechanical effects in the OA pathophysiology that can be taken into account are malalignment and muscle strength. When overweight and malalignment present together, it will give an additional effect. Yusuf and co-workers showed an 18% added effect when overweight and malalignment were * Corresponding author Email: [email protected] Department of Rheumatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands