Osteoarthritis: pathogenesis and therapeutic interventions for a whole joint disease

__Abstract__ Osteoarthritis (OA) is an invalidating disease characterized by progressive cartilage degradation. OA is the most prevalent arthritic disease and leading cause of disability that effects approximately 34% of the population in the United states over age 65. Also in the Netherlands, approximately 30% of persons aged 65 and older are affected in either the hip or knee joint by this severely disabling disease. Due to the obvious cartilage pathology, research has much focused on articular cartilage and chondrocyte pathobiology. Over the years more knowledge has been gained on complex biochemical and biomechanical influences of chondrocyte behavior. During the past decade, however, pathologic cellular and structural changes in subchondral and trabecular bone, ligaments, synovium, supporting musculature, fibrocartilagenous structures such as the meniscus, and intra-articular fat tissue support the idea that osteoarthritis is not just a cartilage problem. In the current dogma, OA is explained as ‘a whole joint disease’ that involves a degenerative continuum between multiple joint tissues and cell types

Citation analysis of orthopaedic literature; 18 major orthopaedic journals compared for Impact Factor and SCImago

<p>Abstract</p> <p>Background</p> <p>One of the disadvantages of the Impact Factor (IF) is self-citation. The SCImago Journal Rank (SJR) indicator excludes self-citations and considers the quality, rather than absolute numbers, of citations of a journal by other journals. The present study re-evaluated the influence of self-citation on the 2007 IF for 18 major orthopaedic journals and investigated the difference in ranking between IF and SJR.</p> <p>Methods</p> <p>The journals were analysed for self-citation both overall and divided into a general group (n = 8) and a specialized group (n = 10). Self-cited and self-citing rates, as well as citation densities and IFs corrected for self-citation (cIF), were calculated. The rankings of the 18 journals by IF and by SJR were compared and the absolute difference between these rankings (ΔR) was determined.</p> <p>Results</p> <p>Specialized journals had higher self-citing rates (p = 0.01, Δmedian = 9.50, 95%CI -19.42 to 0.42), higher self-cited rates (p = 0.0004, Δmedian = -10.50, 95%CI -15.28 to -5.72) and greater differences between IF and cIF (p = 0.003, Δmedian = 3.50, 95%CI -6.1 to 13.1). There was no significant correlation between self-citing rate and IF for both groups (general: r = 0.46, p = 0.27; specialized: r = 0.21, p = 0.56). When the difference in ranking between IF and SJR was compared between both groups, sub-specialist journals were ranked lower compared to their general counterparts (ΔR: p = 0.006, Δmedian = 2.0, 95%CI -0.39 to 4.39).</p> <p>Conclusions</p> <p>Citation analysis shows that specialized orthopaedic journals have specific self-citation tendencies. The correlation between self-cited rate and IF in our sample was large but, due to small sample size, not significant. The SJR excludes self-citations in its calculation and therefore enhances the underestimation in ranking of specialized journals.</p

Properties of commonly used calcium phosphate cements in trauma and orthopaedic surgery

Introduction Half of the population sustains at least one fracture during their lifetime, and the majority of these fractures heal successfully. Successful fracture healing requires the following five elements; (i) osteogenic cells (e.g., osteoblasts), (ii) osteoinductive stimuli (e.g., bone morphogenetic proteins); (iii) an osteoconductive matrix; (iv) adequate blood and nutrient supply, and (v) sufficient mechanical support. One or more elements can be compromised due to the existence of a bone defect. Bone defects are treated with bone grafts in order to avoid insufficient fracture healing. Insufficient fracture healing is encountered in 5–10% of the fractures, resulting in delayed union, malunion, or non-union

FK506 protects against articular cartilage collagenous extra-cellular matrix degradation

Objective: Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in invitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D invitro cultures, and its therapeutic effects in an invivo rat model of OA. Methods: Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated invitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed exvivo using contrast enhanced microCT and histology. Results: FK506 treatment of osteoarthritic chondrocytes invitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity invivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth. Conclusion: FK506 protected cartilage matrix integrity invitro and invivo. Additionally, FK506 treatment invivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA

Congenital Forearm Pseudarthrosis, a Systematic Review for a Treatment Algorithm on a Rare Condition

Background: A congenital forearm pseudarthrosis is a rare condition and is strongly associated with neurofibromatosis type 1. Several surgical techniques are described in the literature, but the most optimal treatment strategy remains unclear. This systematic review aims to develop a treatment algorithm that may aid i

Has the reporting quality of published randomised controlled trial protocols improved since the SPIRIT statement? A methodological study

OBJECTIVES: To determine the reporting quality of published randomised controlled trial (RCT) protocols before and after the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statemen

Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: Correlation with ex-vivo reference standards

Objective: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. Design: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-μCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-μCT X-ray attenuation, sGAG content and collagen content was assessed. Results: CTa X-ray attenuation correlated well with EPIC-μCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36). Conclusions: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research

Delayed endochondral ossification in early medial coronoid disease (MCD): a morphological and immunohistochemical evaluation in growing Labrador retrievers

Medial coronoid disease (MCD) is a common joint disease of dogs. It has a multifactorial aetiology, but the relationship between known causal factors and the disease has yet to be elucidated. As most of the published literature is clinical and it reports changes associated with advanced disease, it is not known whether the changes reflect the cause or consequences of the condition. The aim of this study was to investigate early micromorphological changes occurring in articular cartilage and to describe the postnatal development of the medial coronoid process (MCP) before MCD develops. Three litters of MCD-prone young Labrador retrievers were purpose-bred from a dam and two sires with MCD. Comparisons of the micromorphological appearance of the MCP in MCD-negative and MCD-positive joints demonstrated that MCD was initially associated with a disturbance of endochondral ossification, namely a delay in the calcification of the calcifying zone, without concurrent abnormalities in the superficial layers of the joint cartilage. Cartilage canals containing patent blood vessels were only detected in dogs <12 weeks old, but the role of these channels in impaired ossification requires further investigation. Retained hyaline cartilage might ossify as the disease progresses, but weak areas can develop into cracks between the retained cartilage and the subchondral bone, leading to cleft formation and fragmentation of the MCP