Severity of Diabetes Mellitus and Total Hip or Knee Replacement: A Population-Based Case-Control Study

Contains fulltext : 171491.pdf (publisher's version ) (Open Access)It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.A population-based case-control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78-0.94)) and THR (OR = 0.90 (95% CI = 0.82-0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes

Severity of Diabetes Mellitus and Total Hip or Knee Replacement

Permissions RESEARCH ARTICLE: OBSERVATIONAL STUDY Severity of Diabetes Mellitus and Total Hip or Knee Replacement A Population-Based Case–Control Study Nielen, Johannes T.H. MSc; Emans, Pieter J. PhD; Dagnelie, Pieter C. PhD; Boonen, Annelies PhD; Lalmohamed, Arief PhD; de Boer, Anthonius PhD; van den Bemt, Bart J.F. PhD; de Vries, Frank PhD Editor(s): Roever., Leonardo Author Information Medicine 95(20):p e3739, May 2016. | DOI: 10.1097/MD.0000000000003739 OPEN SDC Metrics Abstract It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality. To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity. A population-based case–control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity. Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78–0.94)) and THR (OR = 0.90 (95% CI = 0.82–0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c. This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes

Prevalence and development of hip and knee osteoarthritis according to American College of Rheumatology criteria in the CHECK cohort

_Background:_ We aimed to evaluate the prevalence of hip and knee osteoarthritis (HOA and KOA) according to American College of Rheumatology (ACR) criteria among participants with suspected early symptomatic osteoarthritis (OA) in the CHECK cohort. We also assessed whether participants not fulfilling ACR criteria at baseline develop ACR-defined OA at 2-year and/or 5-year follow up, and which baseline factors are associated with this development. _Methods:_ The CHECK cohort included 1002 subjects with first presentation of knee and/or hip complaints. The primary outcome was onset of HOA and/or KOA according to the ACR criteria, including the clinical classification criteria and the combined clinical and radiographic classification criteria at 2-year and/or 5-year follow up. _Results:_ Of the participants with hip complaints, 63% (n = 370) were classified as having HOA at baseline according to the ACR criteria. Of those not classified with HOA at baseline, 40% developed HOA according to the clinical or combined clinical/radiographic ACR criteria after 2 and/or 5 years. Up to 92% of participants (n = 829) with knee complaints were classified as having KOA at baseline; of those not classified with KOA at baseline, 55% developed KOA according to the clinical ACR criteria or the clinical/radiographic ACR criteria after 2 and/or 5 years. The following factors were associated with development of HOA: morning stiffness (OR 2.39; 95% CI 1.14-4.98), painful internal rotation (OR 2.53; 95% CI 1.23-5.19), hip flexion < 115° (OR 2.33; 95% CI 1.17-4.64) and erythrocyte sedimentation rate (ESR) < 20 mm/h (OR 2.94; 95% CI 1.13-7.61). No variables were associated with development o

Chondroprotective actions of selective COX-2 inhibitors in vivo: A systematic review

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies

General Introduction

Hyaline cartilage enables us to move our joints even when exposed to high mechanical forces. Other types of cartilage can be found in tissues like the ear, nose, airway etc. In contrast to many other tissues only one type of cell is found in hyaline cartilage this cell is the chondrocyte. Since chondrocytes are capable to produce their own matrix, it is possible to generate cartilage in a laboratory setting. This approach applies to the ideas of tissue engineering. However aspects such as tissue architecture, integration to host tissue, and costs remain of concern when trying to repair and/or produce adequate hyaline cartilage capable to withstand high repetitive mechanical forces

Targeting Inflammatory Processes for Optimization of Cartilage Homeostasis and Repair Techniques

The outcome of cartilage repair techniques is often hampered by unwanted ossification (e.g. Intralesional osteophytes) at the site of the repaired cartilage. Furthermore, stimulating progenitor cells towards chondrocytes and locking them in their desired state is another important hinge point in cartilage repair techniques. Studying the cartilage formation process by endochondral ossification may provide important clues which further enhance cartilage repair techniques in general and may provide crucial information to prevent unwanted ossification in particular. During endochondral ossification mesenchymal progenitors differentiate into proliferative chondrocytes which gradually further differentiate into hypertrophic chondrocytes and finally die by apoptosis; the remaining scaffold is mineralised towards bone. This process takes place in growth plates, during fracture healing and in part during development of articular cartilage, where the endochondral ossification halts at the chondrogenic phase. While inflammation is generally regarded as a negative factor for joint homeostasis and cartilage development, it is also known that inflammation is the first and essential phase of tissue repair in general and bone fracture healing via endochondral ossifcation indeed also depends on haematoma formation and subsequent inflammatory microenvironment. Recently, a growing body of experimental evidence has been published, showing that inflammatory molecules (e.g. Nf-?b, cox-2, inos, tnfa, interleukins) and their down-stream pathways are not only associated with cartilage degeneration, but are also crucially involved in the initiation of the chondrogenic differentiation process and regulation of cartilage hypertrophy and mineralization. The data described in these reports suggest that one could use these inflammatory pathways for cartilage regenerative medicine, as the initiation of chondrogenic differentiation is a crucial moment for progenitor cell-based cartilage repair techniques. Furthermore, targeting inflammatory mediators may also provide a potential pharmacological approach to prevent or decrease chondrocyte hypertrophic differentiation and subsequent bone formation (e.g. Intralesional osteophytes) in cartilage repair techniques.this chapter describes important characteristics of hyaline articular cartilage, drawbacks of current cartilage repair techniques, the process of endochondral ossification and how inflammation related molecules are involved in different phases of endochondral ossification. In addition, this chapter discusses how better insight into these pathways may provide novel molecular tools to modulate chondrogenesis in cartilage regenerative medicine