Joint Remodeling Research Articles

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.

Chemokines and inflammation in osteoarthritis: Insights from patients and animal models.

Evidence has been building that the pathologic drive for development of osteoarthritis (OA) involves more than simple mechanical "wear and tear." Inflammatory mechanisms play an important role in the tissue response to joint injury, and are involved in development of post-traumatic OA. Inflammation also appears integral to the progression of OA, whether post-traumatic or spontaneous, contributing to the evolution of joint tissue degradation and remodeling as well as joint pain. Both patient-based studies and in vivo models of disease have shed light on a number of inflammatory pathways and mediators that impact various aspects of this disease, both structurally and symptomatically. Recent work in this field has implicated inflammatory chemokines in osteoarthritis pathogenesis. Expression of multiple chemokines and their receptors is modulated during disease in both patients and animal models. Although best known for their effects on leukocyte migration and trafficking within the immune system, chemokines can have a wide variety of effects on both motile and non-motile cell types, impacting proliferation, differentiation, and activation of cellular responses. Their role in OA models has also demonstrated diverse effects on disease that exemplify their wide-ranging effects. Understanding how these important mediators of inflammation impact joint disease, and whether they can be targeted therapeutically, is actively being investigated by many groups in this field. This narrative review focuses on evidence published within the last 5 years highlighting chemokine-mediated pathways with mechanistic involvement in osteoarthritis and joint tissue repair. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:735-739, 2017.

Sex differences in the estrogen-dependent regulation of temporomandibular joint remodeling in altered loading.

Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role of estrogen in the disease etiology. Previously, we determined that decreased occlusal loading (DOL) inhibited collagen type II (Col2) expression in the mandibular condylar cartilage (MCC) of female wild-type (WT) mice whereas no change was observed in males. This decrease in chondrogenesis was abolished by estrogen receptor beta (ERβ) deficiency in females. Therefore, the goal of this study was to examine the role of estradiol - ERβ signaling in mediating DOL effects in male mice to further decipher sex differences. Male 21 day-old WT and ERβKO male mice were treated with either placebo or estradiol and exposed to normal or DOL for 4 weeks. Cartilage thickness and cell proliferation, gene expression and immunohistochemistry of chondrogenic markers and estrogen receptor alpha (ERα), and analysis of bone histomorphometry via microCT were completed to ascertain the effect of estradiol on DOL effects to the TMJ. ERβKO male mice lack a MCC phenotype. In both genotypes, estradiol treatment increased Col2 gene expression and trabecular thickness. DOL in combination with estradiol treatment caused a significant increase in Col2 gene expression in both genotypes. The sex differences in DOL-induced inhibition of Col2 expression do not appear to be mediated by differences in estradiol levels between male and female mice. Greater understanding on the role of estrogen and altered loading are critical in order to decipher the sex dimorphism of TMJ disorders.

Granulation Tissue Eroding the Subchondral Bone Also Promotes New Bone Formation in Ankylosing Spondylitis.

We previously suggested that fibroblast-rich granulation tissue eroding the subchondral bone is instrumental in the joint remodeling that occurs in ankylosing spondylitis (AS). The purpose of this study was to determine if this granulation tissue also carries bone-forming capabilities, which we approached by searching for bone-forming cells (hypertrophic chondrocytes, osteoblasts) in its vicinity. We also assessed adipogenic tissue transformation, which has been suggested to be an intermediate feature in AS bone formation based on imaging studies. The facet joints of AS patients, osteoarthritis (OA) patients, and autopsy subjects (controls) were screened for subchondral granulation tissue. We searched for hypertrophic chondrocytes by assessing RUNX-2, type X collagen, and matrix metalloproteinase 13 (MMP-13) expression, for osteoblasts by analyzing RUNX-2, CD56, and type I collagen expression, as well as for signs of new bone formation. Adipocytes and lipid accumulation were assessed in Safranin O-stained sections. In the joints of AS and OA patients, RUNX-2-positive cells were found to be lining the granulation tissue. These cells coexpressed type I collagen but lacked type X collagen and MMP-13 expression, confirming their osteoblastic nature. In 91% of AS joints and in 20% of OA joints (P < 0.05), we observed foci of new bone formation at contact zones between the granulation tissue and the cartilage. Joints containing bony spots showed greater replacement of the adjacent bone marrow by granulation tissue than did joints without bone formation (P < 0.05). The granulation tissue often contained adipocytes and lipid accumulations. Replacement of the subchondral bone marrow by fat tissue was also frequently found but was not associated with new bone formation. The subchondral granulation tissue carries osteoblasts, which promote new bone formation, leading to intraarticular ankylosis of the facet joints in AS.

Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis.

Obesity and associated metabolic diseases collectively referred to as the metabolic syndrome increase the risk of skeletal and synovial joint diseases, including osteoarthritis (OA). The relationship between obesity and musculoskeletal diseases is complex, involving biomechanical, dietary, genetic, inflammatory, and metabolic factors. Recent findings illustrate how changes in cellular metabolism and metabolic signaling pathways alter skeletal development, remodeling, and homeostasis, especially in response to biomechanical and inflammatory stressors. Consequently, a better understanding of the energy metabolism of diarthrodial joint cells and tissues, including bone, cartilage, and synovium, may lead to new strategies to treat or prevent synovial joint diseases such as OA. This rationale was the basis of a workshop presented at the 2016 Annual ORS Meeting in Orlando, FL on the emerging role of metabolic signaling in synovial joint remodeling and OA. The topics we covered included (i) the relationship between metabolic syndrome and OA in clinical and pre-clinical studies; (ii) the effect of biomechanical loading on chondrocyte metabolism; (iii) the effect of Wnt signaling on osteoblast carbohydrate and amino acid metabolism with respect to bone anabolism; and (iv) the role of AMP-activated protein kinase in chondrocyte energetic and biomechanical stress responses in the context of cartilage injury, aging, and OA. Although challenges exist for measuring in vivo changes in synovial joint tissue metabolism, the findings presented herein provide multiple lines of evidence to support a central role for disrupted cellular energy metabolism in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2048-2058, 2016.

The role of Dickkopf-1 in joint remodeling and fibrosis: A link connecting spondyloarthropathies and scleroderma?

Dickkopf-1 (Dkk-1) is a soluble inhibitor of the canonical Wnt pathway, which plays critical roles in embryonic development. Evidence suggests that this molecule regulates several aspects of both bone biology and fibrosis. To provide an overview of our current knowledge of the role of Dkk-1 in joint remodeling and fibrosis. We performed an electronic search (Medline) using the following key words: Dickkopf-1 (or Dkk-1), new bone formation, joint remodeling, ankylosing spondylitis, systemic sclerosis (or scleroderma), and fibrosis, supplemented by a manual search of references from retrieved articles. Dkk-1 is a master regulator of joint remodeling in animal models of arthritis shifting the balance toward new bone formation when its expression is decreased and toward erosion/joint destruction when its expression is increased. In humans, evidence suggests that Dkk-1 may be dysfunctional in patients with ankylosing spondylitis, a prototype bone forming disease. Moreover, data from animal models indicate that Dkk-1 has a protective role against fibrosis in several organs. Recent data suggest that inhibiting the canonical Wnt pathway by overexpression of Dkk-1 could be a way to target TGF-β signaling in fibrotic diseases. Finally, B-cell depletion therapy in systemic sclerosis may exert its effects through TGF-β dependent upregulation of Dkk-1. Dkk-1 appears to play a crucial role in both joint remodeling/ectopic ossification and fibrosis, and may be a prospective therapeutic modality for fibrotic diseases or diseases characterized by pathologic joint remodeling.

Role of vasoactive intestinal peptide in osteoarthritis.

Vasoactive intestinal peptide (VIP) plays important roles in many biological functions, such as, stimulation of contractility in the heart, vasodilation, promoting neuroendocrine-immune communication, lowering arterial blood pressure, and anti-inflammatory and immune-modulatory activity. Osteoarthritis (OA) is a chronic and degenerative bone disease, which is one of the most common causes of disability and most common in both sexes as people become older. Interestingly VIP can prevent chronic cartilage damage and joint remodeling. This review article provides update information on the association of VIP and OA and its treatment. Evidences suggest that VIP is down-regulated in synovial fluid of OA, and VIP down-regulation leads to increase in the production of pro-inflammatory cytokines that might contribute to the pathogenesis of OA; however contradictory reports also exist suggesting that accumulation of VIP in joints can also contribute OA. A number of studies indicated that up-regulation of VIP can counteract the action of pro-inflammatory stimuli and alleviate the pain in OA. More clinical investigations are necessary to determine the biology of VIP and its therapeutic potential in OA that might represent the future standards of care for OA.

Bennett fracture: Arthroscopically assisted percutaneous screw fixation versus open surgery: Functional and radiological outcomes

BackgroundArthroscopically assisted percutaneous screw fixation has been introduced to decrease the invasiveness of treatments for intra-articular fractures. HypothesisArthroscopically assisted percutaneous screw fixation of Bennett fracture simplifies the postoperative course compared to open surgery. Material and methodsTwenty-one Bennett fractures detaching at least one-third of the joint surface were studied retrospectively. Among them, 11 were managed by percutaneous screw fixation and 10 by open surgery. Follow-up was at least 12 months. Clinical and radiological evaluations were performed to assess the development of complications, tourniquet time, immobilisation time, sick-leave time, QuickDASH score, Kapandji score, grip strength, pinch strength, return to work activities, intra-articular screw migration, inadequate reduction, non-union, and joint remodelling. ResultsThe percutaneous group had significantly shorter immobilisation (P<0.0001) and tourniquet (P=0.0068) times. The number of complications was 1 in the percutaneous group and 6 in the open-surgery group. Whereas no adverse radiographic outcomes were found in the percutaneous group, the open-surgery group had 2 cases of inadequate reduction, 3 cases of joint remodelling, and 4 cases of intra-articular screw migration. The number of patients unable to return to their previous work activities was 1 (9%) in the percutaneous group and 3 (30%) in the open-surgery group. DiscussionArthroscopically assisted percutaneous screw fixation seems to ensure a simpler postoperative course, with fewer clinical and radiographic complications, as well as shorter tourniquet and immobilisation times. Level of evidenceIV, retrospective comparative study.

Triterpenoid fraction isolated from Euphorbia tirucalli Linn. ameliorates collagen induced arthritis in Wistar rats

Clarias batrachus collagen extract increases fibroblast cell adhesion, migration and proliferationLek Mun Leong, Ahmad Zorin Sahalan, Liew Huat Tan, Nor Hidayah Mustafa, Nor Fadilah Rajab

The Hypertension of Hemophilia Is Associated with Vascular Joint Remodeling and Cannot be Explained By the Usual Cardiovascular Risk Factors

Patients with hemophilia (PWH) have a higher prevalence of hypertension and intracranial hemorrhage than the general male population. However, the etiology of the hypertension, and to what extent blood pressure and associations with cardiovascular risk factors vary from the general population, is incompletely understood. We therefore investigated the prevalence of hypertension as well as the associations of blood pressure measurements with usual cardiovascular risk factors, in a cross-sectional analysis of a cohort of 486 PWH. The PWH (median age 38 years) came from 3 geographically different areas in the United States. They were compared against males from the contemporary National Health and Nutrition Examination Survey (NHANES), matched for age and race in a 1:5 ratio. Subsequently, at the University of California San Diego, a pilot cohort of PWH (n=28; median age 37 years) was examined prospectively for hypertension and associations with hemophilia-specific risk factors pertaining to joint health. PWH had a significantly higher prevalence of hypertension compared to subjects from NHANES. The prevalence of hypertension was 53.4% in PWH compared to 28.8 % in NHANES (p While the usual cardiovascular risk factors were associated with blood pressure in both PWH and NHANES, they did not account for the differences between the two groups. Whether each risk factor was considered by itself, or in combination with the others in multivariate models, the blood pressure differences remained. Therefore, to elucidate to what extent hemophilia-specific factors might play a role in the pathophysiology of hypertension, we assessed hypertension and blood pressures in association with joint health parameters in a pilot cohort of young adult PWH. These patients underwent prospective baseline examination of 6 joints (both elbows, knees and ankles, n=168) for joint pain (Visual Analogue Scale 0-10), radiographic Pettersson score (maximum score 78), clinical Hemophilia Joint Health Score (HJHS, maximum score 120), severity of hemophilia (severe vs mild/moderate), clotting factor usage, and joint vascular perfusion quantified with Power Doppler (PD, maximum score 54) and high resolution musculoskeletal ultrasound. We found that 54% were hypertensive, similar to the larger cohort. In univariate analysis, PD score was the risk factor most strongly associated with hypertension (p = 0.07). After adjustment for confounders, the odds for hypertension increased by 1.29 (95% CI: 1.04, 1.60; p = 0.02) for each unit increase in PD score. Moreover, there was a strong association of PD scores with SBP when adjusted for confounders. In conclusion, our findings demonstrate that PWH not only have a significantly higher prevalence of hypertension, but also significantly higher blood pressures compared to the general population, even when treated with anti-hypertensive medications. The difference in blood pressures could not be explained by the usual cardiovascular risk factors but appeared to be strongly associated with the degree of vascular changes in the joint. Based on previous findings that vascular remodeling is a prominent feature of hemophilic arthropathy and may be mediated systemically, we postulate that vascular remodeling is associated with the etiology of hypertension in hemophilia. These findings warrant further basic and clinical investigation. Disclosures Kruse-Jarres:Octapharma: Consultancy, Honoraria; CSL Behring: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Baxter: Consultancy, Honoraria. Quon:Novo Nordisk: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Grifols: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Biogen: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Baxter: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. von Drygalski:Novo Nordisk: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Baxalta: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Biogen: Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity9s Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Hematherix Inc: Equity Ownership, Membership on an entity9s Board of Directors or advisory committees, Patents & Royalties; Bayer: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding.

Hip-joint congruity after Dega osteotomy in patients with cerebral palsy: long-term results.

Neurogenic hip dislocation is quite common in children with cerebral palsy (CP). The purpose of this study was to evaluate the long-term outcome of single-event multilevel surgery (SEMLS) in combination with hip reconstruction by using a periacetabular osteotomy as described by Dega concerning post-operative remodeling and plasticity of the femoral head post-operatively. A total of 72 patients with CP as the primary disease and in whom a complex surgical hip reconstruction was performed during SEMLS between 1998 and 2004 were included in the study. There were 45 men and 27 women, with a median age of 7.6 (4.7-16.3) years at the time SEMLS was performed. The mean follow-up time was 7.7years (4.9-11.8). X-rays were taken before and after surgery, and Rippstein 1 and 2 were used for follow-up. As the most reliable value for decentration, migration percentage (MP) as described by Reimers was used. To measure hip-joint cover at follow-up, the centre-edge angle was used. The hip was divided into four different categories according to sphericity and congruity. Using this approach, we could evaluate joint remodeling. Pre-operatively, the mean MP measured by X-ray was 68%. Directly after surgery, this value decreased on average by 12% and at the long-term follow-up was 16.0% on average. A high rate of incongruence was observed on X-rays taken directly after surgery: 66 hip joints were classified as incongruent. The number of aspherical and incongruent joints decreased to 54 at the follow-up examination. Data of our study with high plasticity of the hip joint suggest that even if the femoral head is deformed and a persistent incongruency after surgery is expected, hip reconstruction can be recommended.

Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS.

IntroductionIn ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion. Here, we analyzed whether chondrocyte hypertrophy is involved in cartilage fusion and subsequent joint remodeling in AS.MethodsWe assessed the expression of chondrocyte hypertrophy markers runt-related transcription factor 2 (Runx2), type X collagen (COL10), matrix metalloproteinase 13 (MMP13), osteocalcin and beta-catenin and the expression of positive bone morphogenic proteins (BMPs) and negative regulators (dickkopf-1 (DKK-1)), sclerostin, (wingless inhibitory factor 1 (wif-1)) of chondrocyte hypertrophy in the cartilage of facet joints from patients with AS or osteoarthritis (OA) and from autopsy controls (CO) by immunohistochemistry. Sex determining region Y (SRY)-box 9 (Sox9) and type II collagen (COL2) expression was assessed as indicators of chondrocyte integrity and function.ResultsThe percentage of hypertrophic chondrocytes expressing Runx2, COL10, MMP13, osteocalcin or beta-catenin was significantly increased in OA but not in AS joints compared to CO joints. Frequencies of sclerostin-positive and DKK-1-positive chondrocytes were similar in AS and CO. In contrast, wif-1- but also BMP-2- and BMP-7-expressing and Sox9-expressing chondrocytes were drastically reduced in AS joints compared to CO as well as OA joints whereas the percentage of COL2-expressing chondrocytes was significantly higher in AS joints compared to CO joints.ConclusionsWe found no evidence for chondrocyte hypertrophy within hyaline cartilage of AS joints even in the presence of reduced expression of the wnt inhibitor wif-1 suggesting that chondrocyte hypertrophy is not a predominant pathway involved in joint fusion and remodeling in AS. In contrast, the reduced expression of Sox9, BMP-2 and BMP-7 concomitantly with induced COL2 expression rather point to disturbed cartilage homeostasis promoting cartilage degeneration in AS.

Study of Condylar Asymmetry in Angle Class III Malocclusion With Mandibular Deviation

Differences in the condylar between both sides in class III cases with mandibular deviated are important for the diagnosis, treatment, and retention in this kind of patient. To detect the subtle differences, we analyzed the size, shape, and bone density with three-dimensional reconstructed technology. The symmetry group and the asymmetry group each with 20 cases were chosen according to some standards. The computed tomographic data obtained and three-dimensional model were built with SimPlant software. The distance and angle were measured in the three-dimensional model, and the bone density was measured with the SimPlant software. The differences between the separated side in each group and the difference between the 2 groups were analyzed. In the asymmetry group, some measurement projects of the bilateral condyles showed significant differences, such as the ramal height, condylar perpendicular height, the area of maximum cross section of condylar, condylar medialateral diameter, length of posterior slope, and angle of posterior slope. When the asymmetry group was compared with the symmetry group, the condyles of the asymmetry group showed more asymmetrical variations in morphology, such as the ramal height, the condylar perpendicular height, the area of maximum cross section of condylar, the medialateral diameter, the length of anterior slope, and angle of posterior slope. The bone mineral density of the condylar anterior and condylar medial point was higher in the nondeviated side, and the bone mineral density of the condylar posterior was higher in the deviated side, and no statistically significant difference was found in the symmetry group. In class III malocclusion with mandibular deviation patients, the three-dimensional morphology and bone density of condylar on the deviated side differ from the nondeviated side, which indicates the association between asymmetrical jaw function and joint remodeling.

Distraction, Compression, Extension, and Reduction Combined With Joint Remodeling and Extra-articular Distraction: Description of 2 New Modifications for Its Application in Basilar Invagination and Atlantoaxial Dislocation: Prospective Study in 79 Cases.

Recent strategies for treatment of basilar invagination (BI) and atlantoaxial dislocation (AAD) are based on simultaneous posterior reduction and fixation. To describe new modifications of the procedure distraction, compression, extension, and reduction (DCER), ie, joint remodeling (JRM) and extra-articular distraction (EAD) in patients with "vertical" joints, and to quantify the improvement in joint indices, ie, sagittal inclination (SI), craniocervical tilt (CCT), and coronal inclination. Prospective study (May 2010 to September 2014). Joint indices measured included (normal values): SI (87.15 ± 5.65°), CCT (60.2 ± 9.2°), and coronal inclination (110.3 ± 4.23°). Surgical procedures included DCER alone (performed in SI <100°, group I) or JRM with DCER (in SI: 100-160°, group II), or EAD with DCER in severe BI with almost vertical joints (SI >160°, group III). Seventy-nine patients were selected (mean, 22.5 years of age). All conventional indices improved significantly (P < .001). CCT improved in all groups (P < .01); group I (n = 32): 54 ± 8.7° (preoperative 80.71 ± 12.72°); group II (n = 40): 58 ± 7.0° (preoperative 86.5 ± 14°); group III (n = 7): 62 ± 10.0° (preoperative 104 ± 11.2°). SI improved in both group I and II, P < .01 (cannot be measured in group III). At long-term follow-up (n = 64, 29 ± 8 months, range 12-39 months), the Nurick grade improved to 1.5 ± 0.52 (preoperative: 3.4 ± 0.65; P < .001). DCER seems to be an effective technique in reducing both BI and AAD. JRM and EAD with DCER are useful in moderate to severe BI and AAD (with SI >100°). Joint indices provide useful information for surgical strategy and planning.

The effectiveness of moisturizers for the management of burn scars following severe burn injury: a systematic review protocol

Review question/objective The objective of this review is to identify and synthesize the best available evidence on the effectiveness of moisturizer use for the management of burn scars following severe burn injury. More specifically, the review will focus on the following question(s): What are the recommended types of moisturizers used on scar formation in patients who have sustained a burn injury? What is the effectiveness of moisturizer use on scar outcomes, including formation, breakdown, patient acceptance and water loss, following severe burn injury? Background The common mantra that patients often leave a burns unit with is "moisturize and massage". The modality of scar massage is well-recognized as an important part of burn scar management.1 Following the maturation of scar tissue after a burn injury, massage is commenced as part of the standard care offered to victims of burn injury. The premise behind massage is that it maintains joint mobility, aids softening and remodelling of scar tissue and improves scar elasticity through loosening adhering fibrous tissue, whilst also assisting with pruritus, a common side effect of healing following burn injury.1 When healing skin has gained sufficient strength to tolerate massage with the use of friction, scar massage is routinely performed with the use of lubricants,1 which commonly consist of skin moisturizers. Although existing literature provides guidance on the use of products that are fragrance free and free from other skin irritants,1 little is known in regards to recommendations on the ideal composition of moisturizers for optimal scar management. Products used should not have a negative effect on skin/scar integrity, such as breakdown of the skin. Various products have been reported for use in practice as well as in literature on scar management, include aqueous cream BP, bees wax and herbal oil creams,2 silicone based creams and paraffin/petroleum based products. Aqueous cream BP is a readily available and relatively cheap emollient that is fragrance and color free. Its formulation consists of purified water, white soft paraffin, cetearyl alcohol and sodium lauryl sulfate (SLS), liquid paraffin, and phenoxyethanol. Previously reported as the "standard treatment" for moisturization and massage in some burns units,2 aqueous Cream BP contains SLS, which has been documented as a known skin irritant.3-6 The application of aqueous cream BP in subjects with healthy skin, following the removal of increasing amounts of their stratum corneum, has also been shown to increase transepidermal water loss (TEWL) and disrupt the normal skin maturation process.7 Chronic application of aqueous cream BP was also shown in this study to increase the rate of skin turnover as well as contribute to thinning of the stratum corneum.7 This is of particular concern in burn injury as scar tissue has been shown to have increased TEWL when compared with healthy skin,8. In contrast, a comparison study between aqueous cream BP and bees wax and herbal oil cream indicated that newly healed skin in the bees wax and herbal oil group "appeared supple and moist" when compared to the aqueous BP group. Healing skin in the latter group was reported as appearing dry in contrast.2 Although the study had a small sample size, it did demonstrate that bees wax and herbal oil cream provided a greater reduction in the symptom of itch following burn injury along with a decreased use of antipruritic medications when compared to aqueous cream BP.2 The aim of this study was to compare the effectiveness of both preparations in the management of post burn itch. Anecdotal reports of alternate formulations, including silicone and petroleum based products (such as Vaseline), being used by burns units around the world are often reported at burns symposiums and forums, with their selection appearing to be based on historical practice, clinician preference, patient tolerance or beliefs in herbal medicine. Pressure garment manufacturers often also recommend the avoidance of petroleum based emollients where pressure garments are worn as they may reduce the elasticity of the pressure garment, in turn reducing its effectiveness and the life of the garment. No review on the optimal lubricant for burn scar management has been identified to date via searches of the Cochrane Database of Systematic Reviews, Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports and PubMed database, so this review aims to elucidate the best available evidence on the choice of moisturizer in the management of burn scars.

Biological Reconstruction for Children with Osteosarcoma Around the Knee

Limb salvage in children with primary malignant bone tumours around the knee is challenging, with considerations such as shortening, bone and joint remodeling and high functional demands of active children. The ultimate aim for reconstruction is restoring a stable, painless and mobile joint. With improved survival rates from chemotherapy, reconstructive techniques should ideally last the child's lifespan. We adopted a biological approach by preserving the patients' native joint, with bony defects bridged by fibula grafts supplemented by autoclaved bone grafts infused with bone marrow. We conducted this retrospective review to determine if we were able to meet our objectives of reconstruction. A retrospective review of children with osteogenic sarcoma involving the distal femur or proximal tibia treated at our institution was done. Patients aged 13 years and below at the time of surgery who had undergone a limb salvage procedure that preserved the knee joint were included. Nine patients were identified, 3 males and 6 females. The average age was 10.0 years (range, 7 to 13 years) at the time of surgery. Seven had tumours involving the distal femur while 2 had tumours involving the proximal tibia. There were no cases of local recurrence. Four of the 9 patients died from metastatic disease, the 5 surviving patients have no evidence of disease, and the average follow-up for survivors was 13.2 years. The average active range of motion for the knee joint was 96° (range, 50° to 130°). The average Musculoskeletal Tumour Society (MSTS) score was 26.3 (range, 23 to 30). We have observed this technique of limb salvage offers satisfactory limb function with long-term follow-up.

Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.

To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover. Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA.

Hip Arthroscopic Synovectomy and Labral Repair in a Patient With Rheumatoid Arthritis With a 2-Year Follow-up

The arthroscopic surgical procedures reported previously for a rheumatic hip joint have been primarily performed as diagnostic procedures. Only a few studies have reported the success of arthroscopic surgery in hip joint preservation. We encountered a special case in which joint remodeling was seen in a patient with rheumatoid arthritis treated with biological drugs after hip arthroscopic synovectomy and labral repair. We report the case of a 39-year-old woman with rheumatism, which was controlled with tocilizumab, prednisolone, and tacrolimus. The hip joint showed Larsen grade 3 destruction, and the Harris Hip Score was 55 points. Because of the patient's strong desire to undergo a hip preservation operation, we performed hip arthroscopic synovectomy and repair of a longitudinal labral tear. After 2.5 years, the joint space had undergone rebuilding with improvement to Larsen grade 2, and the Harris Hip Score had improved to 78 points; the patient was able to return to work with the use of 1 crutch. It is possible to perform hip arthroscopic surgery for rheumatoid arthritis with a hip preservation operation with biological drugs.

Histomorphologic and Histomorphometric Characteristics of Zygapophyseal Joint Remodeling in Ankylosing Spondylitis

To unravel the mechanisms that control bony ankylosis in ankylosing spondylitis (AS). Histomorphologic and histomorphometric analyses were performed on zygapophyseal joints obtained from 18 patients with AS, 9 patients with osteoarthritis (OA), and 10 cadaver donors without a rheumatic disease (controls). The proteoglycan content of the cartilage was determined by Safranin O staining and the chondrocyte apoptosis according to caspase 3 expression. AS joints were categorized into 3 groups according to the morphology of the joint surfaces and joint space: group 1 were joints with an open joint space, group 2 were joints with cartilaginous fusion, and group 3 were joints with bony fusion of the joint surfaces. Progressive loss of the joint space from group 1 joints to group 3 joints suggests that this grouping corresponds to sequential stages of joint remodeling. Cartilage thickness and subchondral bone plate thickness declined from group 1 to group 3 (P < 0.01). Increased chondrocyte apoptosis rates were found in groups 1 and 2 (P < 0.05), while in group 3, a reduction in the proteoglycan content was found (P < 0.001). Bone marrow replacement and invasion of the subchondral bone plate by fibrous tissue was found predominantly in AS joints in group 2. Cartilage degeneration, indicated by cartilage thinning, enhanced chondrocyte apoptosis, and proteoglycan loss, and subchondral bone thinning, promoted by invasion of the subchondral bone plate by a fibrous tissue originating from the bone marrow, are hallmarks of joint remodeling in AS.

Effects of Dickkopf-1 on synovitis of rheumatoid arthritis

As an important feature of rheumatoid arthritis (RA), an excessive amount of pro-inflammatory cytokines in RA synovial lesions induces the proliferation of synovial fibroblasts, cartilage erosion and systemic inflammatory immune response. Wnt inhibitor, Dkk-1, contributes to joint remodeling. This study was conducted to explore the role of Dkk-1 in the regulation of pro-inflammatory cytokine secretion. Rheumatoid arthritis synovial fibroblasts (RASF) were cultured from surgical synovial specimens and utilized at passages 4-8. For Dkk-1 silencing assay, Dkk-1-specific siRNA and control scrambled siRNA were transfected into RASF respectively. For Dkk-1 over-expression assay, Dkk-1 plasmid and control vector were transfected into RASFs respectively. Production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8), were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) at pre- and post-transfection respectively. Differences between various groups were evaluated by Wilcoxon signed-rank test. After a treatment of Dkk-1-specific siRNA, RASF exhibited decreased production of pro-inflammatory cytokines in association with down-regulated Dkk-1 levels while Dkk-1 over-expression could up-regulate the production of pro-inflammatory cytokines. The effects were marked when RAFS was activated by TNF-α and IL-1β after transfection. Dkk-1 promotes the production of pro-inflammatory cytokines in RASF so as to exacerbate synovitis of RA. And targeting Dkk-1 may provide a novel therapeutic strategy for RA.