Higher uric acid levels or hyperuricemia is a product of more uric acid production, dysfunctional renal excretion, or a combination of both leading to deposition of urate crystals in the joints and kidneys and has been strongly linked with the development of gout, that is, acute inflammatory arthritis. Uric acid levels have been suggested to depend on multiple factors including lifestyle, diet, alcohol consumption, etc. As these are risk parameters for hyperuricemia and since lifestyle choices vary amongst different Indian communities, we sought to study the prevalence of hyperuricemia in these communities. Also, large-scale data (in terms of gender, age, lifestyle, community) on the prevalence of hyperuricemia in subjects amongst different community populations, Hindu, Muslim, Sikh, and Christian was generated. In a retrospective study conducted at Dr. D. Y. Patil School of Medicine & Research Centre, Navi Mumbai from April 2018 to May 2021, information was gathered from four major communities on a range of indicators including serum uric acid levels followed by a thorough multilevel logistic analysis. We evaluated uric acid levels in 10,378 patients of four different communities. Outcomes were assessed biochemically as well as clinically based on the levels of serum uric acid. The mean serum uric acid levels were highest in Sikhs (7.6 mg%, n=732) followed by Christians (7.3 mg%, n=892) and then by Hindus (5.9 mg%, n=6846) and Muslims (5.6 mg%, n=1908). About 83.7% of Christians consumed meat in a non-vegetarian diet followed by 45.7% Muslims. Percentage of Christians who binge drink were highest whereas percentage of Sikh people in the heavy drinkers’ category were 5.2%. Further, 9.5% Hindus were current smokers followed by 7.8% Sikhs who smoked at present. Overall, our study of 10,378 patients demonstrated that the serum uric acid levels varied from one Indian community to another due to varying external factors like diet, age, lifestyle, and addictions. Thus, lifestyle modification in communities with higher serum uric acid levels is highly advocated and this may reduce the healthcare burden of gouty arthritis in these communities

Osteoarthritis (OA) is a joint degenerative disease leading to chronic pain and disability, thus resulting in a major socioeconomic health burden. OA, which has long been believed to be a cartilage disease, is now considered a whole-joint disorder affecting various anatomical structures, including subchondral bone. Hyaluronic Acid (HA) is commonly used as intra-articular viscosupplementation therapy for its mechanical features and biological effects. Bisphosphonates (BPs) are antiresorptive agents inhibiting recruitment and maturation of osteoclast precursors and activity of mature osteoclasts in the bone. Pre-clinical evidences in the literature, show that intra-articular BPs could impact on OA progression, slowing down or reversing it. The combination of HA biological and mechanical role and Alendronate (ALD) antiresorptive effect could be an interesting strategy for OA treatment. This study describes the synthesis and characterization of FID-134, a new chemical derivative of HA conjugated with ALD by means of a covalent bond, cleavable in physiological condition. FID-134 was synthesized starting from 500 kDa HA: chemical structure and functionalization degree with ALD were investigated by NMR and ICP-OES. Kinetics of ALD release from FID-134 was determined in TRIS buffer at 37°C and compared to a simple mixture of HA+ALD. 20mg/mL formulations of FID-134 and HA+ALD were investigated for viscoelastic properties, in absence and presence of Ca. 2+. ions. The cytotoxicity of FID-134 and free ALD were tested on Saos-2 osteoblasts (ATCC HTB-85) and on primary bovine chondrocytes (PBC) at day 1, 3 and 7. The efficacy of FID-134 was assessed in an inflammatory arthritis in vitro model, where bovine cartilage biopsies were exposed to IL-1β/OSM (10ng/mL) for 3 weeks; at the same time, cartilage explants were treated with FID-134. Collagen release in the surnatants was quantified and compared to controls. FID-134 structure was confirmed by NMR and the 20% mol/mol functionalization degree was determined by ICP-OES. Only about 50% of total bound ALD was released from FID-134 within 7 days, resulting slower compared to HA+ALD mixture. In presence of Ca. 2+. ions, viscoelastic properties of FID-134 dramatically improved, while HA+ALD formulation remained unaffected. The cytotoxicity of ALD was evident at 100 μM on Saos-2 and PBC after 3 days, while no cytotoxicity was observed at 7 days with FID-134. In the cartilage explant model, a strong collagen release was detected in inflammatory conditions after 3 weeks; this tendency was reversed, and collagen release halved when FID-134 was added to the biopsies. The synthesized HA-ALD adduct, FID-134, opens the door for a new approach for OA treatment. The results suggest that FID-134 could be beneficial in cartilage degradation and in restoration of subchondral bone function. Finally, local administration and controlled BP release would likely overcome the drawbacks of ALD oral administration, such as unspecific features and long-term toxic side effects

This edition of the Cochrane Corner looks at the three reviews that were published in the second half of 2023: surgical versus non-surgical interventions for displaced intra-articular calcaneal fractures; cryotherapy following total knee arthroplasty; and physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents.

BACKGROUND. Although osteoarthritis (OA) is not an inflammatory arthritis, a characteristic feature of OA is increased production of pro-inflammatory cytokines, such as interleukin 1beta (IL-1b), by articular chondrocytes. In fact, the degree of articular inflammation is often associated with disease progression; indicating that this process probably contributes to articular damage. Suppressor of cytokine signalling (SOCS) proteins are, as the name suggests, inhibitors of cytokine signalling that function via the JAK/STAT pathway (Janus kinase/signal transducers and activators of transcription). Eight SOCS proteins, SOCS1-SOCS7 and CIS-1 (cytokine-inducible SH2-domain-1 with similar structure to the other SOCS proteins) have been identified, of which, SOCS1-3 and CIS-1 are the best characterised. Reduced expression of SOCS proteins would be predicted to result in increased cytokine responsiveness and thereby could contribute to OA pathology. OBJECTIVES. 1) To compare the expression of SOCS1-3 and CIS-1 in normal and OA human articular chondrocytes and 2) to analyze the effects of IL-1b on SOCS1-3 and CIS-1 mRNA expression. METHODS. Femoral heads were obtained after joint replacement surgery due to OA or following a fracture of the neck of femur (#NOF). The latter patients typically suffer from osteoporosis and their cartilage is widely used as a suitable non-OA control. Chondrocytes from the surface layer of OA or the deep zone of #NOF cartilage were isolated by sequential treatment with trypsin, hyaluronidase and collagenase B. Total RNA was extracted using the Qiagen AllPrep RNA mini kit. Primers were designed for SOCS1-3 and CIS-1 and relative gene expression was determined by real-time RT-PCR (Sybr-green method), normalized to GAPDH. Alternatively, non-OA chondrocytes were isolated from #NOF cartilage and cultured in DMEM/F12/5% FCS, with or without IL-1b plus oncostatin M (OSM, both 2.5 ng/ml) for 3-5 weeks until confluent. Total RNA was extracted as above and the effect of IL-1b on gene expression was determined by qPCR. RESULTS. Expression of SOCS1 and SOCS3 was similar in OA and #NOF chondrocytes. However the expression of SOCS2 and CIS-1 was reduced 13-fold in OA samples compared to #NOF samples (n=5, each group). Expression of one OA patient was set to =1 to determine relative expression. In #NOF chondrocytes, relative expression of SOCS2 was 24.5±20.4 versus 2.5±1.9 in OA chondrocytes and for CIS-1 the values were 26.5±19.5 versus 2.5±1.8 (p<0.01). The in vitro experiments showed that treatment of control #NOF chondrocytes with IL-1b+OSM mimicked the situation in OA: Expression of SOCS2 in cytokine-treated cultures was only 15±10% of that in control cultures and CIS-1 expression was reduced to 16±13% (P<0.01). CONCLUSIONS. To the authors' knowledge this is the first demonstration of reduced expression of SOCS2 and CIS-1, but not SOCS1 or SOCS3, in osteoarthritis. As the SOCS proteins are attenuators of cytokine-mediated processes, reduced expression would be expected to accelerate any inflammatory processes. The fact that IL-1b itself reduces the expression of its suppressors of signalling suggests a potentially damaging positive feedback mechanism that could play a role in OA pathology

The Temporomandibular joint (TMJ) is a complex and important joint for daily activities, and the alloplastic implant is recommended as the best solution, after repeated surgeries, failed autogenous grafts, highly inflammatory metabolic arthritis, fibrous or bony ankyloses. Some complications in total TMJ replacement are associated with implant design, screw fixation failure, implant displacement, fibrous tissue formation, (Speculand, et al. 2000). Some numeric studies evaluate the number of screws needed to guarantee the good fixation and suggest a minimum of three (Ramos et al. 2015), but is a controversy conclusion. The Biomet Microfixation TMJ stock prosthesis, Jacksonville, FL, USA is one of the three or four in the market. Clinical studies published by this device between 2005 and 2015 indicate a success rate of around 84 to 91% with improvements in mouth opening, a decrease in pain score and improved quality of life. The present study analyses experimentally the load transfer of this device. The intact, clean cadaveric ramus was instrumented with four rosettes model (KFG-1-120-D17-11 L3M2S, by Kywoa Electronic Instruments Co™, Japan), one in lateral region, two in lateral region and one in lingual face. The condyle was loaded with the temporal reaction; the load was applied constant velocity of 1mm/min in three continuum phases and with three stops at 100N, 200N and 300N. Next, the Biomet microfixation implant was fixed to the same cadaveric mandibular ramus after resection. The implant was 50mm in length. It was fixed with five 6AL/4V Titanium self-tapping screws with 2.7mm diameter were long enough to establish a bi-cortical support. The screws were screwed into the bone with a torque-screwdriver a constant torque of 0.2Nm. The same rosettes were analyzed before and after implantation and the mandible displacement two. The experimental results for the mandibular ramus present a linear behavior up to 300N load in condyle, with the Biomet implant influencing strain distribution; the maximum influence was near the implant (rosette #4) is around 59%. The average vertical displacement of the mandibular ramus (300N) was measured by machine: 1.18 (±0.02) mm for the intact mandibular ramus and 1.21 (±0.02) mm for the implanted one, which represents a 2.8% differences between the experimental models and reduce of stiffness. The maximum principal strain deformation was observed in the rosette #3 with 1360µε more 20% than the intact mandible for 300N of reaction. The experimental results show that the Biomet TMJ mandibular ramus implant changes the load transfer in the ramus, compared to the intact, with its strain shielding effect. The results indicate the minimum number of screws is three to guarantee a good load transfer but the surface preparation of condyle presents an important factor

We analysed the histological findings in 1146 osteoarthritic femoral heads which would have been considered suitable for bone-bank donation to determine whether pathological lesions, other than osteoarthritis, were present. We found that 91 femoral heads (8%) showed evidence of disease. The most common conditions noted were chondrocalcinosis (63 cases), avascular necrosis (13), osteomas (6) and malignant tumours (one case of low-grade chondrosarcoma and two of well-differentiated lymphocytic lymphoma). There were two with metabolic bone disease (Paget’s disease and hyperparathyroid bone disease) and four with inflammatory (rheumatoid-like) arthritis. Our findings indicate that occult pathological conditions are common and it is recommended that histological examination of this regularly used source of bone allograft should be included as part of the screening protocol for bone-bank collection

Objectives

This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing.

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.

Objectives

Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.

Aims

Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee.

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods.

In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days.

Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response.