Warfarin use and risk of knee and hip replacements.
Annals of the rheumatic diseases
BACKGROUND:Identification of modifiable risk factors and treatments for osteoarthritis (OA) are needed. Warfarin, a vitamin K antagonist, causes fetal and animal model skeletal abnormalities. Vitamin K insufficiency has been associated with OA, but whether warfarin is also detrimental to OA is not known. METHODS:We conducted a nested case-control study using a UK general practitioner electronic medical records database. We identified cases of knee or hip replacement (KR or HR) from among adults with atrial fibrillation newly prescribed either warfarin or direct oral anticoagulants (DOACs). Cases were matched with four controls by age and sex. We assessed the relation of warfarin compared with DOAC use to risk of joint replacement using conditional logistic regression. We also evaluated different durations of warfarin use. RESULTS:We identified 857 subjects with KR or HR (cases), of whom 64.6% were warfarin users, and 3428 matched controls, of whom 56.1% were warfarin users (mean age 75, 47% female). Warfarin users had a 1.59 times higher risk of joint replacement than DOAC users (adjusted OR 1.59, 95% CI 1.31 to 1.92). Longer duration of warfarin use was associated with higher risk of joint replacement in comparison with <1 year of warfarin use. CONCLUSION:Warfarin, a vitamin K antagonist, was associated with greater risk of KR and HR (an indicator for end-stage knee OA) than DOAC use, supporting the importance of adequate vitamin K functioning in limiting OA progression.
10.1136/annrheumdis-2020-219646
Stage-specific and location-specific cartilage calcification in osteoarthritis development.
Annals of the rheumatic diseases
OBJECTIVES:This study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies. METHODS:Normal and OA cartilages were serially sectioned for micro-CT, scanning electron microscopy with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, focused ion beam scanning electron microscopy, high-resolution electron energy loss spectrometry with transmission electron microscopy, nanoindentation and atomic force microscopy to analyse the structural, compositional and mechanical properties of cartilage in OA progression. RESULTS:We found that OA progressed by both top-down calcification at the joint surface and bottom-up calcification at the osteochondral interface. The top-down calcification process started with spherical mineral particle formation in the joint surface during early-stage OA (OA-E), followed by fibre formation and densely packed material transformation deep into the cartilage during advanced-stage OA (OA-A). The bottom-up calcification in OA-E started when an excessive layer of calcified tissue formed above the original calcified cartilage, exhibiting a calcified sandwich structure. Over time, the original and upper layers of calcified cartilage fused, which thickened the calcified cartilage region and disrupted the cartilage structure. During OA-E, the calcified cartilage was hypermineralised, containing stiffer carbonated hydroxyapatite (HAp). During OA-A, it was hypomineralised and contained softer HAp. This discrepancy may be attributed to matrix vesicle nucleation during OA-E and carbonate cores during OA-A. CONCLUSIONS:This work refines our current understanding of the mechanism underlying OA progression and provides the foothold for potential therapeutic targeting strategies once the location-specific cartilage calcification features in OA are established.
10.1136/ard-2022-222944
Prognostic model to predict the incidence of radiographic knee osteoarthritis.
Annals of the rheumatic diseases
OBJECTIVE:Early diagnosis of knee osteoarthritis (KOA) in asymptomatic stages is essential for the timely management of patients using preventative strategies. We develop and validate a prognostic model useful for predicting the incidence of radiographic KOA (rKOA) in non-radiographic osteoarthritic subjects and stratify individuals at high risk of developing the disease. METHODS:Subjects without radiographic signs of KOA according to the Kellgren and Lawrence (KL) classification scale (KL=0 in both knees) were enrolled in the OA initiative (OAI) cohort and the Prospective Cohort of A Coruña (PROCOAC). Prognostic models were developed to predict rKOA incidence during a 96-month follow-up period among OAI participants based on clinical variables and serum levels of the candidate protein biomarkers APOA1, APOA4, ZA2G and A2AP. The predictive capability of the biomarkers was assessed based on area under the curve (AUC), and internal validation was performed to correct for overfitting. A nomogram was plotted based on the regression parameters. Model performance was externally validated in the PROCOAC. RESULTS:282 participants from the OAI were included in the development dataset. The model built with demographic, anthropometric and clinical data (age, sex, body mass index and WOMAC pain score) showed an AUC=0.702 for predicting rKOA incidence during the follow-up. The inclusion of ZA2G, A2AP and APOA1 data significantly improved the model's sensitivity and predictive performance (AUC=0.831). The simplest model, including only clinical covariates and ZA2G and A2AP serum levels, achieved an AUC=0.826. Both models were internally cross-validated. Predictive performance was externally validated in an independent dataset of 100 individuals from the PROCOAC (AUC=0.713). CONCLUSION:A novel prognostic model based on common clinical variables and protein biomarkers was developed and externally validated to predict rKOA incidence over a 96-month period in individuals without any radiographic signs of disease. The resulting nomogram is a useful tool for stratifying high-risk populations and could potentially lead to personalised medicine strategies for treating OA.
10.1136/ard-2023-225090
The role of biomechanics in the initiation and progression of OA of the knee.
Englund Martin
Best practice & research. Clinical rheumatology
The knee is one of the most common joints affected by osteoarthritis (OA), frequently with clinical presentation by middle age or even earlier. Accumulating evidence supports that knee OA progression is often driven by biomechanical forces, and the pathological response of tissues to such forces leads to structural joint deterioration, knee symptoms and reduced function. Well-known biomechanical risk factors for progression include joint malalignment and meniscal tear. The high risk of OA after knee injury demonstrates the critical role of biomechanical factors also in incident disease in susceptible individuals. However, our knowledge of the contributing biomechanical mechanisms in the development of early disease and their order of significance is limited. Part of the problem is our current lack of understanding of early-stage OA, when it starts and how to define it.
10.1016/j.berh.2009.08.008
Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association.
Altman R,Asch E,Bloch D,Bole G,Borenstein D,Brandt K,Christy W,Cooke T D,Greenwald R,Hochberg M
Arthritis and rheumatism
For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.
10.1002/art.1780290816
Knee biomechanics and contralateral knee osteoarthritis progression after total knee arthroplasty.
Gait & posture
BACKGROUND:Despite the success rate of Total Knee Arthroplasty (TKA), many patients undergo contralateral TKA. It is possible that altered gait mechanics after unilateral TKA play a role in the progression of contralateral OA progression. RESEARCH QUESTION:The purpose of this study was to identify biomechanical predictors of radiographic OA progression in the contralateral (non-surgical) knee after unilateral (primary/initial) TKA. In addition, this study quantified for patients who had contralateral OA progression. METHODS:Biomechanical outcomes were collected 6-24 months after unilateral primary TKA and were used to predict changes in contralateral OA severity at follow-up. Participants were divided into "Progressor" and "Non-Progressor" groups based on changes in Kellgren-Lawrence (KL) OA grade and Joint Space Width (JSW) between baseline and follow-up testing sessions. Biomechanical factors during walking were peak knee adduction moment, knee flexion/extension excursions, knee angle at initial foot contact, and peak knee flexion/extension. Multiple independent t-tests were used to examine the magnitude of differences in biomechanical variables between the groups. Logistic regression was used to examine the association between the biomechanical predictors and change in KL scores and JSW. RESULTS:The mean time between surgery and follow-up x-rays was 8.8 (2.4) years. Of 40 participants, 62.5-78% had contralateral radiographic knee OA progression by follow-up. There were no significant differences in the biomechanical variables between groups. For the regression analysis, none of the biomechanical variables were found to be predictors for contralateral OA progression. SIGNIFICANCE:Although abnormal biomechanics are known risk factors for primary knee OA, it is possible that the mechanisms that result in OA progression of the contralateral limb are different than primary knee OA progression. Future work should evaluate other objective measures of OA progression and determine if cumulative measures of joint loading are related to OA worsening.
10.1016/j.gaitpost.2021.10.020
Coronal Plane Alignment of the Knee (CPAK) classification.
MacDessi Samuel J,Griffiths-Jones William,Harris Ian A,Bellemans Johan,Chen Darren B
The bone & joint journal
AIMS:A comprehensive classification for coronal lower limb alignment with predictive capabilities for knee balance would be beneficial in total knee arthroplasty (TKA). This paper describes the Coronal Plane Alignment of the Knee (CPAK) classification and examines its utility in preoperative soft tissue balance prediction, comparing kinematic alignment (KA) to mechanical alignment (MA). METHODS:A radiological analysis of 500 healthy and 500 osteoarthritic (OA) knees was used to assess the applicability of the CPAK classification. CPAK comprises nine phenotypes based on the arithmetic HKA (aHKA) that estimates constitutional limb alignment and joint line obliquity (JLO). Intraoperative balance was compared within each phenotype in a cohort of 138 computer-assisted TKAs randomized to KA or MA. Primary outcomes included descriptive analyses of healthy and OA groups per CPAK type, and comparison of balance at 10° of flexion within each type. Secondary outcomes assessed balance at 45° and 90° and bone recuts required to achieve final knee balance within each CPAK type. RESULTS:There was similar frequency distribution between healthy and arthritic groups across all CPAK types. The most common categories were Type II (39.2% healthy vs 32.2% OA), Type I (26.4% healthy vs 19.4% OA) and Type V (15.4% healthy vs 14.6% OA). CPAK Types VII, VIII, and IX were rare in both populations. Across all CPAK types, a greater proportion of KA TKAs achieved optimal balance compared to MA. This effect was largest, and statistically significant, in CPAK Types I (100% KA vs 15% MA; p < 0.001), Type II (78% KA vs 46% MA; p = 0.018). and Type IV (89% KA vs 0% MA; p < 0.001). CONCLUSION:CPAK is a pragmatic, comprehensive classification for coronal knee alignment, based on constitutional alignment and JLO, that can be used in healthy and arthritic knees. CPAK identifies which knee phenotypes may benefit most from KA when optimization of soft tissue balance is prioritized. Further, it will allow for consistency of reporting in future studies. Cite this article: 2021;103-B(2):329-337.
10.1302/0301-620X.103B2.BJJ-2020-1050.R1
Early-stage symptomatic osteoarthritis of the knee - time for action.
Mahmoudian Armaghan,Lohmander L Stefan,Mobasheri Ali,Englund Martin,Luyten Frank P
Nature reviews. Rheumatology
Osteoarthritis (OA) remains the most challenging arthritic disorder, with a high burden of disease and no available disease-modifying treatments. Symptomatic early-stage OA of the knee (the focus of this Review) urgently needs to be identified and defined, as efficient early-stage case finding and diagnosis in primary care would enable health-care providers to proactively and substantially reduce the burden of disease through proper management including structured education, exercise and weight management (when needed) and addressing lifestyle-related risk factors for disease progression. Efforts to define patient populations with symptomatic early-stage knee OA on the basis of validated classification criteria are ongoing. Such criteria, as well as the identification of molecular and imaging biomarkers of disease risk and/or progression, would enable well-designed clinical studies, facilitate interventional trials, and aid the discovery and validation of cellular and molecular targets for novel therapies. Treatment strategies, relevant outcomes and ethical issues also need to be considered in the context of the cost-effective management of symptomatic early-stage knee OA. To move forwards, a multidisciplinary and sustained international effort involving all major stakeholders is required.
10.1038/s41584-021-00673-4