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Rheumatoid arthritis (RA) is a systemic immune-mediated disease characterized by joint inflammation and destruction. The disease typically affects small joints in the hands and feet, later progressing to involve larger joints such as the knees, shoulders, and hips. While the reasons for these joint-specific differences are unclear, distinct epigenetic patterns associated with joint location have been reported. In this study, we evaluated the unique epigenetic landscapes of fibroblast-like synoviocytes (FLS) from hip and knee synovium in RA patients, focusing on the expression and regulation of Homeobox (HOX) transcription factors. These highly conserved genes play a critical role in embryonic development and are known to maintain distinct expression patterns in various adult tissues. We found that several HOX genes, especially HOXD10, were differentially expressed in knee FLS compared with hip FLS. Epigenetic differences in chromatin accessibility and histone marks were observed in HOXD10 promoter between knee and hip FLS. Histone modification, particularly histone acetylation, was identified as an important regulator of HOXD10 expression. To understand the mechanism of differential HOXD10 expression, we inhibited histone deacetylases (HDACs) with small molecules and siRNA. We found that HDAC1 blockade or deficiency normalized the joint-specific HOXD10 expression patterns. These observations suggest that epigenetic differences, specifically histone acetylation related to increased HDAC1 expression, play a crucial role in joint-specific HOXD10 expression. Understanding these mechanisms could provide insights into the regional aspects of RA and potentially lead to therapeutic strategies targeting specific patterns of joint involvement during the course of disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1 , however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3 , p16 , ADAMTS4 , and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3 , Adamts5 , p16 , Il-6 , and Tnfα , and decreased expression of Col2a1 and -an . These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

Background: Novel methods for diagnosing periprosthetic joint infection (PJI) are currently being explored. Mass spectrometry (MS) is an approach that can detect whole-protein changes in synovial fluid and may represent a promising method., Methods: Between March 2017 and July 2018, we successively collected synovial fluid samples from patients who were undergoing diagnostic hip or knee aspiration because PJI was suspected. A PJI diagnosis was based on the modified Musculoskeletal Infection Society (MSIS) criteria. Cluster analysis and receiver operating characteristic (ROC) curves were used to evaluate the results, which were quantitatively confirmed with parallel reaction monitoring in another patient group who underwent aspiration between August 2018 and January 2019., Results: A total of 117 synovial samples, including 51 PJI and 66 non-PJI samples, were analyzed with liquid chromatography-tandem MS (LC-MS/MS). The cluster analysis sensitivity and specificity based on differentially expressed proteins were 0.961 (95% confidence interval [CI], 0.854 to 0.993) and 0.924 (95% CI, 0.825 to 0.972), respectively. Myeloid nuclear differentiation antigen (MNDA) and polymorphonuclear leukocyte serine protease 3 (PRTN3) were the 2 most important markers for detecting PJI. The areas under the curves (AUCs) of MNDA and PRTN3 were 0.969 (95% CI, 0.936 to 1.000) and 0.900 (95% CI, 0.844 to 0.956), respectively. When MNDA and PRTN3 were combined as variables of a predictive model to diagnose PJI, the AUC reached 0.975 (95% CI, 0.943 to 1.000). Our parallel reaction monitoring-based quantitative analysis of another 40 synovial samples confirmed this result., Conclusions: MS could be a powerful tool for diagnosing PJI using proteome information or 2 specific markers, MNDA and PRTN3. The parallel reaction monitoring strategy simplified the PJI detection process and provided quantitative results with similar conclusions., Clinical Relevance: The clinical application of MS adds a new powerful tool for the diagnosis of PJI, and the parallel reaction monitoring strategy lays a foundation for the clinical application of MS., Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/G534)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control., Design: Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC)., Results: 303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage., Conclusions: Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interests., (Copyright © 2021 Osteoarthritis Research Society International. All rights reserved.)

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, MMP2 (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cai, Liang, Xiao, Huang, Zhu, Shi, Ouyang and Yang.)

Objective: Hip cartilage quality is essential for the success of joint-preserving surgery for osteonecrosis. This study aimed to characterize cartilage changes in osteonecrosis of femoral head (ONFH) using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)., Design: Fifteen asymptomatic (control) and 60 ONFH subjects were included in this study. The ONFH subjects were stratified in accordance with the Association Research Circulation Osseous (ARCO) classification ( n = 15 hips per ARCO stage). All participant hips were investigated using dGEMRIC and theT1Gd data were collected and analyzed., Results: T1Gd value was significantly lower in the ONFH group (365.1 ± 90.5 ms; range 200-498 ms) compared with the control group (546.1 ± 26.0 ms; range 504-580 ms) ( P < 0.001). The T1Gd values of ARCO stage I-IV ONFH were 460.2 ± 17.3 ms (439-498 ms), 408.9 ± 43.4 ms (337-472 ms), 359.9 ± 34.5 ms (303-412 ms), 231.5 ± 15.1 ms (200-253 ms), respectively. Decreased T1Gd value was found to correlate significantly with increased ONFH severity ( P < 0.001). T1Gd value in collapse stage was significantly lower than that of noncollapse stage (295.7 ± 70.3 ms [range 200-412 ms] vs. 434.6 ± 41.7 ms [range 337-498 ms]; P < 0.001)., Conclusions: dGEMRIC identified hip cartilage as abnormal in ONFH, even at early-stage, as represented by decreased T1Gd, and this was further aggravated by ONFH collapse.

In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While loss of Piezo2 in chondrogenic or osteogenic lineages does not lead to human-like skeletal abnormalities, its loss in proprioceptive neurons leads to spine malalignment and hip dysplasia. To validate the non-autonomous role of proprioception in hip joint morphogenesis, we studied this process in mice mutant for proprioceptive system regulators Runx3 or Egr3. Loss of Runx3 in the peripheral nervous system, but not in skeletal lineages, leads to similar joint abnormalities, as does Egr3 loss of function. These findings expand the range of known regulatory roles of the proprioception system on the skeleton and provide a central component of the underlying molecular mechanism, namely Piezo2.

The osteoporosis was common complication of ankylosing spondylitis (AS), but it was frequently unrecognized in the initial stage of the disease. This study was to compare areal bone mineral density (BMD) of hip joints in early AS patients with that in healthy controls, to explore the progress of bone loss in cortex and spongiosa in early AS.Quantitative computed tomography (QCT) of hip was performed in 60 AS patients (modified New York criteria for AS, with grade 2 sacroiliitis in computed tomography) and 57 healthy controls. The QCT measurements of AS patients were compared with the measurements of healthy controls.The AS patients had lower areal BMD in cortical bone and total bone of proximal femur in early AS patients (P < .01), than the controls. But there were not significant different of areal BMD in spongiosa of proximal femur between the early AS patients and healthy controls. Strong correlations were found between body mass index BMI, areal BMD in cortical bone (rs = 0.410, P < .001; rs = 0.422, P < .001) and total bone (rs = 0.368, P < .001; rs = 0.266, P = .003) both in AS patients and healthy controls.The results indicate that osteopenia/osteoporosis is general in early stage of AS. What is more, the osteopenia/osteoporosis in cortex is earlier than in spongiosa of proximal femur in early AS.

The objective of this study was to describe the normal variation of bone marrow fat content in the proximal femur considering the influence of side, age, sex and body mass index using fat fraction MRI. From September 2012 to July 2016, the MRI of 131 patients (258 hips) considered to have a normal MRI appearance were retrospectively evaluated. Patient records were searched to allow calculation of the body mass index (BMI). Water-fat based chemical shift MRI was available for all patients included. Proton density fat fraction maps were calculated, and measurements were performed in the femoral epiphysis, intertrochanteric region, and greater trochanter. The influence of patient age, sex, hip side and BMI on fat fraction values was assessed. Fat fraction was significantly different in the different locations evaluated (P = 0.0001). Patient sex and age significantly influenced fat fraction values in all regions evaluated (P < 0.02) with the exception of the epiphysis for sex (p = 0.07). In all locations, PDFF values were higher in men compared to women (3.3%, 4.4% and 13.1% higher in the epiphysis, greater trochanter and intertrochanteric region respectively). The intertrochanteric region presented the lowest fat fraction values with the highest variation compared to the greater trochanter and the epiphysis. BMI only influenced fat fraction values in the intertrochanteric region of females over 42 years old (P = 0.014). The interobserver variability of the measurements performed was considered to be excellent (ICC = 0.968). In conclusion, patient sex, age, and measurement location significantly influenced fat fraction values indicating that specific standards of reference are needed depending on these factors.

Objective: To preliminarily explore the diagnostic potential of ultrasound (US) in detecting calcium pyrophosphate (CPP) crystal deposits at the hip joint in a cohort of patients with CPP deposition disease (CPPD) who were previously evaluated by conventional radiography (CR) and to assess the sensitivity and specificity as well as the agreement between US and CR in the evaluation of hip CPP crystal deposits., Methods: Fifty consecutive patients with definite CPPD and 40 age/sex/body mass index-matched disease control subjects who had undergone hip CR within the previous 6 months were enrolled. Bilateral hip US examination was carried out to assess the presence of CCP crystal deposits at the acetabular labrum fibrocartilage and at the femoral head's hyaline cartilage. Two independent radiologists evaluated the presence of hip CPP crystal deposits on CR in both groups., Results: US findings indicative of CPP crystal deposits were found in at least 1 hip in 45 of 50 patients with CPPD (90.0%) and in 73 of 100 hips (73.0%). CPP crystal deposits were more frequently found at the acetabular labrum fibrocartilage than at the femoral head's hyaline cartilage (72% and 17% of the hips in patients with CPPD, respectively). US and CR sensitivity was 90% and 86%, whereas US and CR specificity was 85% and 90%, respectively. Total agreement between the US and CR findings was 77.8%., Conclusion: Our results provide new evidence supporting US as a first-line, sensitive, safe, and reliable imaging technique in detecting CPP crystal deposits at the hip level., (© 2018, American College of Rheumatology.)

Objectives: To investigate the prevalence of the ultrasound findings indicative of monosodium urate crystal deposits at the hip joint in patients with gout and to explore the association between the ultrasound findings and the clinical and serological features., Methods: Bilateral ultrasound assessment of the hip joint was carried out in 40 consecutive patients with gout, diagnosed according to the latest Gout American College of Rheumatology/European League Against Rheumatism classification criteria, and 25 disease controls. Ultrasound evidence of crystal deposits was obtained using the Outcome Measures in Rheumatology definitions: hip intra-articular aggregates and/or tophi, and "double contour" sign over the hyaline cartilage of the femoral head., Results: The ultrasound examination revealed crystal deposits in at least one hip in 17 out of 40 patients (42.5%) with gout, and in 2 out of 25 disease controls (8.0%) (P = 0.0029). Aggregates, tophi, and "double contour" sign were found in at least one hip in 13 (32.5%), 6 (15.0%) and 6 (15.0%) out of 40 patients with gout, respectively. A moderate association between disease duration (P = 0.004, Rpb = 0.442), number of gouty "attacks" in the previous year (P = 0.029, Rpb = 0.346), presence of subcutaneous tophi (P = 0.037, V = 0.330) and ultrasound crystal deposits was found., Conclusion: Our results indicate that detecting monosodium urate crystals by ultrasound is common at hip joint in patients with gout., (Copyright © 2019 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Different adaptation rates have been reported in studies involving ankle exoskeletons designed to reduce the metabolic cost of their wearers. This work aimed to investigate energetic adaptations occurring over multiple training sessions, while walking with a soft exosuit assisting the hip joint. The participants attended five training sessions within 20 days. They walked carrying a load of 20.4 kg for 20 minutes with the exosuit powered and five minutes with the exosuit unpowered. Percentage change in net metabolic cost between the powered and unpowered conditions improved across sessions from -6.2 ± 3.9% (session one) to -10.3 ± 4.7% (session five), indicating a significant effect associated with training. The percentage change at session three (-10.5 ± 4.5%) was similar to the percentage change at session five, indicating that two 20-minute sessions may be sufficient for users to fully adapt and maximize the metabolic benefit provided by the exoskeleton. Retention was also tested measuring the metabolic reduction five months after the last training session. The percent change in metabolic cost during this session (-10.1 ± 3.2%) was similar to the last training session, indicating that the adaptations resulting in reduced metabolic cost are preserved. These outcomes are relevant when evaluating exoskeletons' performance on naïve users, with a specific focus on hip extension assistance.

Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes. This is likely responsible for the increased apoptosis of chondrocytes and pathological destruction of cartilage. Further investigation has revealed that LINC00341 interacts with miR-141 to suppress its functional binding to the 3'-untranslated region of YY1-associated factor 2 (YAF2) messenger RNA. Aberrant downregulation of LINC00341 thus may ultimately lead to inhibition of the YAF2 protein, which has been implicated to be an antiapoptotic factor. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects chondrocytes by preventing apoptosis under normal conditions. The results will help further explore the molecular details pertaining to the progression of OA and stimulate efforts to develop effective therapies., (© 2019 Wiley Periodicals, Inc.)

Canine hip dysplasia and developmental dysplasia of the human hip share demographic, phenotypic, and clinical features including the predisposition to develop osteoarthritis in affected joints. To support the results of genetic mapping studies for CHD and its concomitant osteoarthritis with functional information, we performed RNA-seq on hip capsule and teres ligament of affected and unaffected dogs. RNA seq showed that expressed genes segregated according age, capsule or ligament, and hip phenotype. Expression of HHIP, DACT2, and WIF1 was significantly higher in capsule from control hips than dysplastic hips indicating a disruption of the hedgehog signaling pathway. Expression of SPON 1, a key component of the WNT pathway, was increased significantly in both dysplastic capsule and ligament while FBN2 and EMILIN3 were significantly increased in dysplastic capsule. Of genes associated with human hip osteoarthritis, expression of ACAN, IGF1, CILP2, COL11A1, COL8A1, and HAPLN was increased significantly in dysplastic capsule. The significant increase in expression of PLA2F, TNFRSF, TMEM, and IGFBP in dysplastic capsule indicated an injury response. Gene set enrichment analysis revealed that genes involved in extracellular matrix structure, epithelial to mesenchymal transition, myogenesis, growth factor signaling, cancer and immune pathways were enriched in dysplastic capsule. For teres ligament from dysplastic joints, genes in retinoic signaling pathways and those encoding extracellular matrix molecules, but not proteoglycans, were enriched. Hip tissues respond to abnormal mechanics early in dysplastic hip development and these pathways present targets for intervention in the early synovitis and capsulitis secondary to canine and human hip dysplasia. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:313-324, 2019., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Anatomical knowledge dictates that regional anaesthesia after total hip arthroplasty requires blockade of the hip articular branches of the femoral and obturator nerves. A direct femoral nerve block increases the risk of fall and impedes mobilisation. We propose a selective nerve block of the hip articular branches of the femoral nerve by an ultrasound-guided injection in the plane between the iliopsoas muscle and the iliofemoral ligament (the iliopsoas plane). The aim of this study was to assess whether dye injected in the iliopsoas plane spreads to all hip articular branches of the femoral nerve., Methods: Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve., Results: In 10 dissections (67% [95% confidence interval: 38-88%]), the injectate was contained in the iliopsoas plane staining all hip articular branches of the femoral nerve without spread to motor branches. In four dissections (27% [8-55%]), the injection was unintentionally made within the iliopectineal bursa resulting in secondary spread. In one dissection (7% [0.2-32%]) adhesions partially obstructed the spread of dye., Conclusion: An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could generate a selective sensory nerve block of the articular branches of the femoral nerve without motor blockade., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated., Methods: We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type., Results: Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis., Conclusions: In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

We report a case of a 53-year-old man who presented with a diagnostic dilemma mimicking septic arthritis. It is important to consider the diagnosis of calcific peri-arthritis clinically and recognize the hallmarks on radiograph and magnetic resonance imaging as this disease process resolves completely with conservative management like in our patient, and does not require operative intervention., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Adverse Reaction to Metal Debris (ARMD) is still a major reason for revision surgeries in patients with metal-on-metal (MoM) hip replacements. ARMD consists of a wide range of alterations in periprosthetic tissues, most important of which are metallosis, inflammation, pseudotumors and necrosis. Studies investigating histopathological findings and their association to implant wear or indirect measures of wear have yielded inconsistent results. Therefore, we aimed to investigate bearing surface wear volume, whole blood and synovial fluid metal ion concentrations, histopathological findings in periprosthetic tissues and their associations., Methods: Seventy-eight patients with 85 hips revised for ARMD were included in the study. Prior to revision surgery, all patients had whole blood chromium and cobalt ion levels assessed. In revision surgery, a synovial fluid sample was taken and analyzed for chromium and cobalt. Periprosthetic tissue samples were taken and analyzed for histopathological findings. Explanted implants were analyzed for bearing wear volume of both acetabular cup and femoral head components., Results: Volumetric wear of the failed components was highly variable. The total wear volume of the head and cup had a strong correlation with whole blood chromium and cobalt ion concentrations (Cr: ρ = 0.80, p < 0.001 and Co: ρ = 0.84, p < 0.001) and a bit weaker correlation with fluid chromium and cobalt ion concentrations (Cr: ρ = 0.50, p < 0.01 and Co: ρ = 0.41, p = 0.027). Most tissues displayed only low-to-moderate amounts of macrophages and lymphocytes. Total wear volume correlated with macrophage sheet thickness (ρ = 0.25, p = 0.020) and necrosis (ρ = 0.35, p < 0.01). Whole blood chromium and cobalt ion concentrations had similar correlations. Lymphocyte cuff thickness did not correlate with either total wear volume or whole blood metal ion concentrations, but correlated with the grade of necrosis., Conclusions: Bearing wear volume correlated with blood metal ion levels and the degree of necrosis and macrophage infiltration in periprosthetic tissues suggesting a dose-response relationship. Whole blood metal ion levels are a useful tool for clinician to estimate bearing wear and subsequent tissue response.

Objective: The objective of the work to determine the diagnostic role of the three phase bone scintigraphy (3 F BS) in the early prediction of paraendoprosthetic complications of the hip and knee joints of the participants in clean up workers of Chornobyl accident., Material and Methods: The 3 F BS method were investigated the radionuclide kinetic parameters of the inclusion and distribution of radiopharmaceuticals (RF) in damaged joints in the 75 male clean up workers., Results: It was established that calculating the quantitative indices of kinetics of the drug at various stages of the 3 F BS allowed to determine statistically significant differences in metabolic changes in focal lesions in articular structures. Thus, the differential diagnostic capabilities of the radionuclide method of examination of patients with arthroplasty of the hip and knee joints are elevated., Conclusions: The kinetics of osteotropic RF in the foci of fixing the damaged hip and knee joints in the infectious and inflammatory processes is characterized by the predominance of retention and specific accumulation of the drug in the early static phase and the delayed static phase of the 3 F BS compared with the centers of fixation of RF in deforming osteoarthroses, which correlates with the differences in destructive reparative processes in them., (M. M. Tkachenko, P. O. Korol.)

Background: Trochanteric bursa (TB) injection with local anesthetic and corticosteroid is a treatment for patients suffering from greater trochanteric pain syndrome. Both landmark (LM)-guided and ultrasound (US)-guided methods have been used, but their accuracies have not been determined. This study examined the accuracy of these injections with cadaveric dissection., Methods: Twenty-four hip specimens were randomized to receive TB injections with methylene blue under either LM-guided or US-guided approach. After dissection, the locations of the dye were classified into 3 categories: intrabursal, extrabursal, or combined intrabursal and extrabursal. The presence of dye in the intrabursal space with or without extrabursal leak was considered a successful injection. Accuracy was defined as the percentage of successful injection., Results: The accuracies of the LM-guided and US-guided injection were 0.67 (95% confidence interval 0.35-0.90) and 0.92 (95% confidence interval 0.62-1.00), respectively, with no significant difference., Conclusions: This is the first cadaveric study examining the accuracy of both the US-guided and LM-guided techniques for TB injection. Future clinical studies are required to compare the outcomes of LM-guided and US-guided greater trochanteric pain syndrome injection.

Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibers with microfibrillar or network-like aggregates and penetrating extrafibrillar proteoglycan matrix. The biomechanical function of the proteoglycan matrix and the collagen fibers are to absorb compressive and tensional loads, respectively. Here, we are focusing on the suprastructural organization of collagen fibrils and the degradation process of their hierarchical organized fiber architecture studied at high resolution at the authentic location within cartilage. We present electron micrographs of the collagenous cores of such fibers obtained by an improved protocol for scanning electron microscopy (SEM). Articular cartilages are permeated by small prototypic fibrils with a homogeneous diameter of 18 ± 5 nm that can align in their D-periodic pattern and merge into larger fibers by lateral association. Interestingly, these fibers have tissue-specific organizations in cartilage. They are twisted ropes in superficial regions of knee joints or assemble into parallel aligned cable-like structures in deeper regions of knee joint- or throughout hip joints articular cartilage. These novel observations contribute to an improved understanding of collagen fiber biogenesis, function, and homeostasis in hyaline cartilage., Competing Interests: The authors have declared that no competing interests exist.

Articular cartilage consists of chondrocytes and two major components, a collagen-rich framework and highly abundant proteoglycans. Most prior studies defining the zonal distribution of cartilage have extracted proteins with guanidine-HCl. However, an unextracted collagen-rich residual is left after extraction. In addition, the high abundance of anionic polysaccharide molecules extracted from cartilage adversely affects the chromatographic separation. In this study, we established a method for removing chondrocytes from cartilage sections with minimal extracellular matrix protein loss. The addition of surfactant to guanidine-HCl extraction buffer improved protein solubility. Ultrafiltration removed interference from polysaccharides and salts. Almost four-times more collagen peptides were extracted by the in situ trypsin digestion method. However, as expected, proteoglycans were more abundant within the guanidine-HCl extraction. These different methods were used to extract cartilage sections from different cartilage layers (superficial, intermediate, and deep), joint types (knee and hip), and disease states (healthy and osteoarthritic), and the extractions were evaluated by quantitative and qualitative proteomic analyses. The results of this study led to the identifications of the potential biomarkers of osteoarthritis (OA), OA progression, and the joint specific biomarkers.

In hypoparathyroidism, areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is above average, and skeletal indices by bone biopsy are abnormal. We used high-resolution peripheral quantitative computed tomography (HRpQCT) and finite element analyses (FEA) to further investigate skeletal microstructure and estimated bone strength. We studied 60 hypoparathyroid subjects on conventional therapy using DXA, HRpQCT, and FEA of the distal radius and tibia compared with normative controls from the Canadian Multicentre Osteoporosis Study. In hypoparathyroid women and men, areal BMD was above average at the lumbar spine and hip sites by DXA; radial BMD was also above average in hypoparathyroid women. Using HRpQCT, cortical volumetric BMD was increased in the hypoparathyroid cohort compared with controls at both the radius and tibia. Cortical porosity was reduced at both sites in pre- and postmenopausal women and at the tibia in young men with a downward trend at the radius in men. At the tibia, trabecular number was increased in premenopausal women and men and trabecular thickness was lower in women. Ultimate stress and failure load at both sites for the hypoparathyroid subjects were similar to controls. Using a linear regression model, at both radius and tibia, each increment in age decreased ultimate stress and failure load, whereas each increment in duration of hypoparathyroidism increased these same indices. These results provide additional evidence for the critical role of parathyroid hormone in regulating skeletal microstructure. Longer disease duration may mitigate the adverse effects of age on estimated bone strength in hypoparathyroidism., (© 2015 American Society for Bone and Mineral Research.)

Background: Osteoarthritis may result from abnormal mechanics leading to biochemically mediated degradation of cartilage. In a dysplastic hip, the periacetabular osteotomy (PAO) is designed to normalize the mechanics and our initial analysis suggests that it may also alter the cartilage biochemical composition. Articular cartilage structure and biology vary with the depth from the articular surface including the concentration of glycosaminoglycans (GAG), which are the charge macromolecules that are rapidly turned over and are lost in early osteoarthritis. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) enables noninvasive measurement of cartilage GAG content. The dGEMRIC index represents an indirect measure of GAG concentration with lower values indicating less GAG content. GAG content can normally vary with mechanical loading; however, progressive loss of GAG is associated with osteoarthritis. By looking at the changes in amounts of GAG in response to a PAO at different depths of cartilage, we may gain further insights into the types of biologic events that are occurring in the joint after a PAO., Questions/purposes: We (1) measured the GAG content in the superficial and deep zones for the entire joint before and after PAO; and (2) investigated if the changes in the superficial and deep zone GAG content after PAO varied with different locations within the joint., Methods: This prospective study included 37 hips in 37 patients (mean age 26 ± 9 years) who were treated with periacetabular osteotomy for symptomatic acetabular dysplasia and had preoperative and 1-year follow up dGEMRIC scans. Twenty-eight of the 37 also had 2-year scans. Patients were eligible if they had symptomatic acetabular dysplasia with lateral center-edge angle < 20° and no or minimal osteoarthritis. The change in dGEMRIC after surgery was assessed in the superficial and deep cartilage zones at five acetabular radial planes., Results: The mean ± SD dGEMRIC index in the superficial zone fell from 480 ± 137 msec preoperatively to 409 ± 119 msec at Year 1 (95% confidence interval [CI], -87 to -54; p < 0.001) and recovered to 451 ± 115 msec at Year 2 (95% CI, 34-65; p < 0.001), suggesting that there is a transient event that causes the biologically sensitive superficial layer to lose GAG. In the deep acetabular cartilage zone, dGEMRIC index fell from 527 ± 148 msec preoperatively to 468 ± 143 msec at Year 1 (95% CI, -66 to -30; p < 0.001) and recovered to 494 ± 125 msec at Year 2 (95% CI, 5-32; p = 0.008). When each acetabular radial plane was looked at separately, the change from before surgery to 1 year after was confined to zones around the superior part of the joint. The only significant change from 1 to 2 years was an increase in the superficial layer of the superior zone (1 year 374 ± 123 msec, 2 year 453 ± 117 msec, p < 0.006)., Conclusions: This study suggests that PAO may alter the GAG content of the articular cartilage with a greater effect on the superficial zone compared with the deeper acetabular cartilage zone, especially at the superior aspect of the joint. Some surgeons have observed that surgery itself can be a stressor that can accelerate joint degeneration. Perhaps the decrease in dGEMRIC index seen in the superficial layer may be a catabolic response to postsurgical inflammation given that some recovery was seen at 2 years. The decrease in dGEMRIC index in the deep layer seen mainly near the superior part of the joint is persistent and may represent a response of articular cartilage to normalization of increased mechanical load seen in this region after osteotomy, which may be a normal response to alteration in loading., Clinical Relevance: This study looks at the biochemical changes in the articular cartilage before and after a PAO for dysplastic hips using MRI in a similar manner to using histological methods to study alterations in articular cartilage with mechanical loading. Although PAO alters alignment and orientation of the acetabulum, its effects on cartilage biology are not clear. dGEMRIC provides a noninvasive method of assessing these effects.

Objective: First, to study how markers of matrix metabolism, inflammation markers, and adipokines relate to (superior) cam deformity and (possible) cam impingement of the hip. Second, to investigate whether they can identify subjects with cam deformity that are at risk of future hip osteoarthritis (OA)., Method: In a cohort of 1002 subjects (CHECK), (superior) cam deformity was defined by an alpha angle >60° on anteroposterior pelvic radiographs and (possible) cam impingement by a cam deformity together with internal hip rotation ≤20°. Hip OA at 5-year follow-up was defined by Kellgren and Lawrence grade ≥2 or total hip replacement., Results: Subjects with (superior) cam deformity and (possible) cam impingement showed lower levels of bone turnover markers (uCTX-I, uNTX-I, sPINP, sOC) than those without. Cam deformity was positively associated with future hip OA, but associations were weaker at high levels of bone turnover. sCOMP and sHA levels were higher in subjects with cam deformity, while other cartilage and synovium markers were not. Some markers of inflammation (pLeptin, pAdiponectin, and erythrocyte sedimentation rate) were lower in presence of cam deformity and cam impingement, but high-sensitivity C-reactive protein was not. Most associations depended largely on gender differences., Conclusion: Bone metabolism may be relevant in the pathogenesis of (superior) cam deformity and in the development of (superior) cam deformity into hip OA. Subjects with cam deformity and cam impingement surprisingly showed lower levels of inflammation markers and adipokines. Associations of cartilage turnover markers with cam deformity and cam impingement were less obvious., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Presents a new import-substituting the composition of the powder mixture 60 medicinal plants and dead bees. In prednisolonbuy models of osteoporosis have shown dose-dependent regenerative effects bone and cartilage of the hip joints of mice. Unwanted side effects when taking composition was observed. It is assumed the possibility of effective application of the composition as a complementary treatment for osteoporosis.

In the article the results of clinical researches of efficiency of preparation of Cocarnit are resulted for patients after endoprosthesis of large joints. It is routine that for patients, receiving preparation of Cocarnit after the operation period there was a decline in the amount of complaints of patients on the total somatical state. Preparation of Ccocarnit was positively estimated outside patients, meaningful by-reactions, serving reason of abolition of preparation, was not marked. At the reception preparation of Cocarnit greater part of investigational laboratory indexes (table of contents of glucose, β-lipoproteines, total chondroitisulfates, TBC-productes (malonic dyaldehyde), activity of aspartataminotransferase, alkaline phosphatase and β-glutamyltranspeptidase), the indexes of clinical blood test and leucocytar indexes during a supervision did not have reliable differences from such as the persons of the control group, that confirms good bearab leness of the indicated preparation. Application preparation of Cocarnit for patients in composition the chart of treatment of patients after endoprosthesis of large joints brought maintenance over of cholesterol to the decline, glycoproteins, TBC-products (malonic dyaldehyde), activity of alaninaminotransferase, that specifies on normalizing influence of the indicated preparation in relation to the basic types of exchange of matters.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD. Serial MRI was performed on 28 patients. T2-weighted and gadolinium-enhanced MR images were used to assess synovial effusion and synovial enhancement (hyperemia) over time. A multiple-cytokine assay was used to determine the levels of 27 inflammatory cytokines and related factors present in the synovial fluid from 13 patients. MRI analysis showed fold increases of 5.0 ± 3.3 and 3.1 ± 2.1 in the synovial fluid volume in the affected hip compared to the unaffected hip at the initial and the last follow-up MRI, respectively. The mean duration between the initial and the last MRI was 17.7 ± 8.3 months. The volume of enhanced synovium on the contrast MRI was increased 16.5 ± 8.5 fold and 6.3 ± 5.6 fold in the affected hip compared to the unaffected hip at the initial MRI and the last follow-up MRI, respectively. In the synovial fluid of the affected hips, IL-6 protein levels were significantly increased (LCPD: 509 ± 519 pg/mL, non-LCPD: 19 ± 22 pg/mL; p = 0.0005) on the multi-cytokine assay. Interestingly, IL-1β and TNF-α levels were not elevated. In the active stage of LCPD, chronic hip synovitis and significant elevation of IL-6 are produced in the synovial fluid. Further studies are warranted to investigate the role of IL-6 on the pathophysiology of synovitis in LCPD and how it affects bone healing., (© 2015 American Society for Bone and Mineral Research.)

Objective: This retrospective study was carried out to determine the typical patterns of (18)F-FDG uptake in uncomplicated total hip arthroplasty (THA)., Subjects and Methods: (18)F-FDG-PET images of 62 asymptomatic THA patients who had undergone whole body scanning were evaluated for this retrospective study. The uptake was assessed qualitatively as positive or negative in the head/neck and the stem of the prosthesis. There were 76 hip prosthesis scans (34 left side and 42 right) and the average time following surgery was 75 months (range from 40 days to 372 months). Furthermore, the time course after surgery was subdivided into 3 time interval groups: Group I less than 2 years, Group II between 2 to 5 years, Group III more than 5 years. The regions of assessment were: head region including acetabulum and femoral head, femoral neck, trochanter, and femoral shaft., Results: In patients who demonstrated increased peri-prosthetic (18)F-FDG uptake (59 of the 76 hip scans), the activity was confined to the femoral neck and proximal femoral shaft with the majority in the neck regions alone: 68% (40 of 59). Majority of the uptake was noted in the femoral neck, proximal shaft and trochanteric regions., Conclusion: Uptake of (18)F-FDG in the asymptomatic patients with THA is commonly visualized and appears to be confined to the proximal segment of the prosthesis with minimal or no activity in its femoral segment.

Background: Innovations in biologics offer great promise in the treatment of patients with orthopaedic conditions and in advancing our ability to monitor underlying disease pathophysiology. Our understanding of the pathophysiology of hip osteoarthritis (OA) has improved significantly in the last decade. Femoroacetabular impingement (FAI) and hip dysplasia are increasingly recognized and treated as forms of prearthritic hip disease, yet the inability of radiographic and MR imaging to identify patients before the onset of irreversible articular cartilage injury limits their use for early diagnosis and treatment of patients with these conditions. Molecular biomarkers, as objectively measureable indicators of the pathophysiology of hip OA, have the potential to improve diagnosis, disease staging, and prognosis of hip OA and prearthritic hip disease. Although research into molecular biomarkers of hip OA has been conducted, investigations in prearthritic hip disease have only recently begun., Questions/purposes: The purpose of our review was to assess the use of molecular biomarkers in the pathophysiology of hip OA, including (1) diagnosis; (2) disease staging; and (3) prognosis. We additionally aimed to summarize the available literature investigating the use of biomarkers in (4) prearthritic hip disease, including FAI and hip dysplasia., Methods: We conducted a systematic review of molecular biomarkers associated with hip OA or prearthritic hip disease by searching four major electronic databases for keywords "hip", "osteoarthritis", "biomarker", and all synonyms. The search terms "femoroacetabular impingement" and "hip dysplasia" were also included. The biologic source of biomarkers was limited to serum, plasma, urine, and synovial fluid. The literature search yielded a total of 2740 results. Forty studies met all criteria and were included in our review. Studies were categorized regarding their relevance to (1) diagnosis; (2) disease staging; (3) prognosis; and/or (4) prearthritic hip disease., Results: Biomarker studies were characterized as relevant to diagnosis (16 studies), disease staging (15 studies), prognosis (11 studies), and prearthritic hip disease (three studies). Sixteen different biomarkers demonstrated associations relevant to the diagnosis of hip OA, 16 biomarkers demonstrated similar associations for disease staging, and six for prognosis. Six biomarkers seemed to be the most promising, demonstrating associations with hip OA in multiple studies, including: urinary level of type II collagen telopeptide (n = 5 studies), serum cartilage oligomeric protein (n = 4 studies), and serum C-reactive protein (n = 4 studies). Only three studies investigated the role of biomarkers in prearthritic hip disease, including two in FAI and one in unspecified etiology of pain. There were no studies about biomarkers in hip dysplasia., Conclusions: Molecular biomarkers are increasingly investigated for their use in evaluating the pathophysiology of hip OA, but less so for prearthritic hip disease. Several biomarkers have demonstrated significant associations with hip OA across multiple studies. Further validation of these biomarkers is needed to assess their clinical use and potential application to prearthritic hip disease.

Objective: To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts., Methods: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR)., Results: The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene., Conclusions: Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation., (Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Cadmium is an element with proven direct and indirect toxic effects on bones. Zinc affects the content of cadmium in the human body. These elements show antagonistic interactions. The aim of the research was to determine the levels of cadmium and zinc in the hip joint tissues and interactions between these elements. The study group consisted of 91 subjects, 66 women and 25 men. The tissues were obtained intraoperatively during hip endoprosthetic surgery. The levels of cadmium and zinc were assayed by the atomic absorption spectrophotometry (AAS) method. The analysis of the content of cadmium and zinc in different parts of the hip joint, i.e., articular cartilage, cortical bone, and cancellous bone of the femoral head as well as the articular capsule and a fragment of the cancellous bone taken from the intertrochanteric region of the femoral bone showed significant differences. The cancellous bone was found to have the highest potential to accumulate the elements studied, whereas part of the articular capsule the lowest. Higher levels of cadmium and zinc were observed in samples obtained from men. Patients with bone fractures had higher cadmium content than those with osteoarthritis. The study on the content of cadmium and zinc in the tissues of the hip joint is one of the primary research biomonitoring.

18F-fluoride positron emission tomography (18F-fluoride PET) is a functional imaging modality used primarily to detect increased bone metabolism. Increased 18F-fluoride PET uptake suggests an association between increased bone metabolism and load stress at the subchondral level. This study therefore examined the relationship between equivalent stress distribution calculated by finite element analysis and 18F-fluoride PET uptake in patients with hip osteoarthritis. The study examined 34 hips of 17 patients who presented to our clinic with hip pain, and were diagnosed with osteoarthritis or pre-osteoarthritis. The hips with trauma, infection, or bone metastasis of cancer were excluded. Three-dimensional models of each hip were created from computed tomography data to calculate the maximum equivalent stress by finite element analysis, which was compared with the maximum standardized uptake value (SUVmax) examined by 18F-fluoride PET. The SUVmax and equivalent stress were correlated (Spearman's rank correlation coefficient ρ=0.752), and higher equivalent stress values were noted in higher SUVmax patients. The correlation between SUVmax and maximum equivalent stress in osteoarthritic hips suggests the possibility that 18F-fluoride PET detect increased bone metabolism at sites of stress concentration. This study demonstrates the correlation between mechanical stress and bone remodeling acceleration in hip osteoarthritis., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objectives: To explore the association between S100A8/A9 serum levels with clinical and structural characteristics of patients with established knee, hip, or hand osteoarthritis (OA)., Method: A cross-sectional exploratory study was conducted with 162 OA patients. Measures for pain, stiffness, and function included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire or the Australian Canadian Osteoarthritis Hand (AUSCAN) Index and for structural abnormalities, osteophytes and joint space narrowing grades. The association between S100A8/A9 and clinical or structural characteristics was analysed using linear regression or logistic regression where appropriate., Results: The mean age of the OA patients was 56 years, 71% were female, and 61% had a Kellgren and Lawrence (K&L) score ≥ 2. The serum S100A8/A9 level did not differ between knee, hip, and hand OA patients and no association was found between serum S100A8/A9 and clinical characteristics. The serum S100A8/A9 level was negatively associated with the sum score of osteophytes after adjusting for sex and body mass index (BMI) [adjusted β -0.015, 95% confidence interval (CI) -0.030 to 0.001, p = 0.062] and positively associated with erythrocyte sedimentation rate (ESR) > 12 mm/h (adjusted OR 1.002, 95% CI 1.000-1.004 p = 0.049) for each increase in S100A8/A9 of 1 ng/mL. For hand OA patients, a negative association of S100A8/A9 with sum score of joint space narrowing was found (adjusted β -0.007, 95% CI -0.016 to 0.001, p = 0.099)., Conclusions: The results from this cross-sectional exploratory study do not support an important role for serum S100A8/A9 levels as a biomarker for clinical and structural characteristics in established knee, hip, and hand OA patients. The inverse association with structural abnormalities and the positive association with ESR may reflect inflammatory synovial processes in patients with OA before structural abnormalities occur.

The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity.

The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

Purpose: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia)., Materials and Methods: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood-lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis., Results: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood-lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication)., Conclusion: Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk-benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

Objective: To identify expression profiles (EP) associated with aseptic loosening of total knee arthroplasty (TKA) and to compare them with EP observed in total hip arthroplasty (THA), and primary knee and hip osteoarthritis (OA)., Design: Gene EP of TNF, IL-6, IL-8, CHIT1, BMP4, CCL3, CCL18, MMP9, RANKL, OPG, DC-STAMP and SOCS3 were assessed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on tissues retrieved from patients with aseptically failed TKA (n = 21), THA (n = 41) and primary knee (n = 20) and hip (n = 17) OA. Immunohistochemistry was applied to localize the proteins., Results: When compared to knee OA, the pseudosynovial tissue in TKA exhibit (1) elevation of alternative macrophage activation marker (CHIT1), chemokine (IL-8), and a proteolytic enzyme (MMP9); (2) downregulation of pro-inflammatory cytokine (TNF), osteoclastic regulator (OPG) and a stimulator of bone formation (BMP4); (3) no difference in IL-6, CCL3, CCL18, RANKL, DC-STAMP and SOCS3. The EP in TKA differed from EP in aseptically failed THA by lower CCL3 and DC-STAMP mRNA and protein expression. EP of all studied inflammatory and osteoclastogenic molecules were similar in knee and hip OA., Conclusions: Comparing to OA, aseptic loosening of TKA is associated with upregulated expression of CHIT1, IL-8 and MMP9, dysregulated RANKL:OPG ratio and low levels of inflammatory cytokines. Similar cytokine profiles were associated with primary knee and hip OA. Further research is required to explain the differences in CCL3 and DC-STAMP expression between failed TKA and THA., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To perform a genome-wide DNA methylation study to identify DNA methylation changes in osteoarthritic (OA) cartilage tissue., Methods: The contribution of differentially methylated genes to OA pathogenesis was assessed by bioinformatic analysis, gene expression analysis, and histopathologic severity correlation. Genome-wide DNA methylation profiling of >485,000 methylation sites was performed on eroded and intact cartilage from within the same joint of 24 patients undergoing hip arthroplasty for OA. Genes with differentially methylated CpG sites were analyzed to identify overrepresented gene ontologies, pathways, and upstream regulators. The messenger RNA expression of a subset of differentially methylated genes was analyzed by reverse transcription-polymerase chain reaction. Histopathology was graded by modified Mankin score and correlated with DNA methylation., Results: We identified 550 differentially methylated sites in OA. Most (69%) were hypomethylated and enriched among gene enhancers. We found differential methylation in genes with prior links to OA, including RUNX1, RUNX2, DLX5, FURIN, HTRA1, FGFR2, NFATC1, SNCAIP, and COL11A2. Among these, RUNX1, HTRA1, FGFR2, and COL11A2 were also differentially expressed. Furthermore, we found differential methylation in approximately one-third of known OA susceptibility genes. Among differentially methylated genes, upstream regulator analysis showed enrichment of TGFB1 (P = 4.40 × 10(-5) ) and several microRNAs including miR-128 (P = 4.48 × 10(-13) ), miR-27a (P = 4.15 × 10(-12) ), and miR-9 (P = 9.20 × 10(-10) ). Finally, we identified strong correlations between 20 CpG sites and the histologic Mankin score in OA., Conclusion: Our data implicate epigenetic dysregulation of a host of genes and pathways in OA, including a number of OA susceptibility genes. Furthermore, we identified correlations between CpG methylation and histologic severity in OA., (Copyright © 2014 by the American College of Rheumatology.)

Teriparatide is a skeletal anabolic treatment for patients with osteoporosis at high risk for fracture. Because adequate clinical trials have not yet been conducted to assess the efficacy of teriparatide for reducing the risk of hip fracture, we review here the literature regarding how treatment with teriparatide affects the hip in patients with osteoporosis. Teriparatide increases cancellous bone volume, improves bone architecture, and - uniquely among osteoporosis treatments - increases cortical thickness and cortical porosity. By bone scan and positron emission tomography, teriparatide increases bone formation throughout the skeleton, including the hip. Consistent with these findings, studies using dual-energy X-ray absorptiometry and quantitative computed tomography for longitudinal assessment of changes at the hip have consistently shown increases in areal and volumetric bone mineral density, cortical thickness, and finite element-estimated hip strength in patients treated with teriparatide. Finally, in clinical fracture-outcome trials, treatment with teriparatide has been shown to reduce the risk of nonvertebral fracture, a composite endpoint that includes hip fracture. Taken together, this body of evidence suggests that teriparatide positively affects the hip in patients with osteoporosis., (Copyright © 2014. Published by Elsevier Inc.)

Forces generated in the muscles and tendons actuate the movement of the skeleton. Accurate estimation and application of these musculotendon forces in a continuum model is not a trivial matter. Frequently, musculotendon attachments are approximated as point forces; however, accurate estimation of local mechanics requires a more realistic application of musculotendon forces. This paper describes the development of mapped Hill-type muscle models as boundary conditions for a finite volume model of the hip joint, where the calculated muscle fibres map continuously between attachment sites. The applied muscle forces are calculated using active Hill-type models, where input electromyography signals are determined from gait analysis. Realistic muscle attachment sites are determined directly from tomography images. The mapped muscle boundary conditions, implemented in a finite volume structural OpenFOAM (ESI-OpenCFD, Bracknell, UK) solver, are employed to simulate the mid-stance phase of gait using a patient-specific natural hip joint, and a comparison is performed with the standard point load muscle approach. It is concluded that physiological joint loading is not accurately represented by simplistic muscle point loading conditions; however, when contact pressures are of sole interest, simplifying assumptions with regard to muscular forces may be valid., (Copyright © 2014 John Wiley & Sons, Ltd.)

Fondaparinux, indirect factor Xa (FXa) inhibitor, is recommended for thromboprophylaxis for high-risk patients undergoing major orthopedic surgery. We evaluated the prothrombotic state and anticoagulant intensity of fondaparinux (2.5 mg daily) after total hip replacement (THR). Twenty patients underwent THR - seven bilateral and 13 unilateral. Blood samples were collected preoperatively and at 6 h, 8 h (2 h after fondaparinux), 1 day (12-14 h after fondaparinux), and 4 weeks (12-14 h after fondaparinux) postoperatively. Antithrombin (AT), fibrinogen, factor VIII activity, coagulation times, thrombin-AT (TAT) complex, D-dimer, C-reactive protein, prothrombinase-induced clotting time (PiCT) and anti-Xa activity were measured. The latter two were also tested after plasma spiking with fondaparinux 0-1.25 μg/ml. In spiked prophylactic fondaparinux samples (0-0.25 μg/ml), PiCT and anti-Xa activity correlated (r = 0.84) better than in the patient samples (r = 0.35). On the first day, anti-Xa activity and PiCT dissociated, and PiCT lost sensitivity for fondaparinux. AT decreased but stayed within the normal range, whereas TAT complex and D-dimer peaked at 6 h as signs of thrombin generation. On the first postoperative day, TAT and D-dimer halved. Bilateral THR associated with higher TAT and D-dimer levels up to 4 weeks. Perioperative FVIII levels were not affected, but were elevated in both groups (range 191-211%) after 4 weeks. Anti-Xa activity detected prophylactic fondaparinux with higher sensitivity than PiCT in vitro, but even more so in vivo. Thus, PiCT is not the method of choice to assess fondaparinux at least in association with THR. THR, bilateral more than unilateral, increased thrombin generation and D-dimer 7-11-fold early after surgery. Factor VIII activity and D-dimer remained elevated even after 4 weeks despite the compliant thromboprophylaxis with fondaparinux.

Volume and morphology of chondrocytes in osteoarthritic human hip joint articular cartilage were characterized, and their relationship to tissue structure and function was determined. Human osteochondral articular cartilage samples (n=16) were obtained from the femoral heads of nine patients undergoing total hip arthroplasty due to osteoarthritis (OA). Superficial chondrocytes (N=65) were imaged in situ with a confocal laser scanning microscope at 37 °C. This was followed by the determination of the mechanical properties of the tissue samples, depth-wise characterization of cell morphology (height, width; N=385) as well as structure and composition of the tissues using light microscopy, digital densitometry, Fourier transform infrared microspectroscopy and polarized light microscopy. Significant correlations were found between the cell volume and the orientation angle associated with the collagen fibers (r=0.320, p=0.009) as well as between the cell volume and the initial dynamic modulus of the tissue (r=-0.305, p=0.013). Furthermore, the depth-dependent chondrocyte aspect ratio (height/width) correlated significantly with the orientation angle of the collagen fibers and with the tissue's proteoglycan content (r=0.261 and r=0.228, respectively, p<0.001). Our findings suggest that the orientation angle of the collagen fibers primarily controls chondrocyte volume and shape in osteoarthritic human hip joint articular cartilage.

Osteoporosis is a serious and multifactorial disease. The number of people affected with osteoporosis is increasing due to the lengthening of life expectancy. Currently, unlike the genetic, nutritional and hormonal factors that have been the focus of most studies of osteoporosis, mechanical stimuli that potentially can produce an increase in bone strength have not been well studied. Studies suggest that the relationship between the health of the bone and mechanical stimuli occurs through bone adaptive remodeling, which is activated by means of the shear stress transmitted by the interstitial fluid flow. The present work consists of a finite element analysis of a femur to simulate the basic movements of the hip (flexion, extension, abduction, and adduction) to compare the shear stresses in a common zone of fracture and in the critical mechanical strength zones of the femoral head. A comparison of the distribution and magnitude of the shear stresses was performed to estimate the movement that could induce a more rapid adaptive bone remodeling. This study is the first step in the development of a physical therapy for a preventive rehabilitation that helps to prevent patients with low bone mineral density to avoid suffering osteoporosis hip fractures. The finite element model was constructed using a free-access three-dimensional standardized femur obtained from the Instituti Ortopedici Rizzoli, Bologna, Italy. The mechanical properties and the muscular forces were obtained from a specialized bibliography. We conclude that the movements that exhibit a higher mean value and a good shear stress distribution in the femoral neck are hip extension and abduction.

Low bone mineral density (BMD) is a risk factor for osteoporosis. Osteoporosis is more prevalent in females than in males. So far, the pathophysiological mechanisms underlying osteoporosis are unclear. Peripheral blood monocytes (PBMs) are precursors of bone-resorbing osteoclasts. This study aims to identify PBM-expressed proteins (genes) influencing hip BMD in humans. We utilized three independent study cohorts (N=34, 29, 40), including premenopausal Caucasians with discordant hip BMD. We studied PBM proteome-wide protein expression profiles in cohort 1 and identified 57 differentially expressed proteins (DEPs) between low vs. high BMD subjects. One protein gelsolin (GSN), after validation by Western blotting, was subject to follow-up. We compared GSN mRNA level in PBM between low vs. high BMD subjects in cohorts 2 and 3. We genotyped SNPs across GSN in 2286 unrelated Caucasians (cohort 4) and 1627 Chinese (cohort 5) and tested their association with hip BMD in females and males, respectively. We discovered and validated that GSN protein expression level in PBM was down-regulated 3.0-fold in low vs. high BMD subjects (P<0.05). Down-regulation of GSN in PBM in low BMD subjects was also observed at mRNA level in both cohort 2 and cohort 3. We identified that SNP rs767770 was significantly associated with hip BMD in female Caucasians (P=0.0003) only. Integrating analyses of the datasets at DNA, RNA, and protein levels from female Caucasians substantiated that GSN is highly significant for hip BMD (P=0.0001). We conclude that GSN is a significant gene influencing hip BMD in female Caucasians., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To investigate the distribution pattern of sonographically guided iliopsoas (IP) injections in an unembalmed cadaveric model., Methods: A single experienced operator completed 10 sonographically guided IP injections in 5 unembalmed cadaveric pelvic specimens (4 male and 1 female; ages 55-95 years; body mass indices, 15.5-27.5 kg/m(2)) using a previously described in-plane, lateral-to-medial approach short axis to the tendon. Each injection consisted of 7 mL of a 20% dilution of contrast material injected between the IP tendon and the acetabular rim using a 22-gauge, 87.5-mm (3½-in) needle. To facilitate interpretation of contrast patterns, 2 additional injections were performed on single hips: sonographically guided 14 mL contrast-latex IP injection and sonographically guided superficial IP "peritendinous" injection with 7 mL of contrast-latex. Immediately before and after each injection, fluoroscopic images were obtained with a fixed C-arm equipped with coned beam computed tomography. After each injection, radiographic images were evaluated by a board-certified, fellowship-trained musculoskeletal radiologist to determine injectate distribution. Specimens receiving contrast-latex injections were dissected 48 hours after injection to determine the anatomic location of the injectate., Results: Nine of 10 IP injections (90%) produced characteristic "U-shaped" flow patterns covering 50% to nearly 100% of the IP tendon circumference and resembling previously published IP bursograms. One injection was excluded because the majority of the latex was within the pectineus muscle, likely due to technical factors. Latex flowed an average of 5.3 cm (range, 0.3-7.9 cm) cephalad and 5.2 cm (range, 1.0-7.5 cm) caudad to the acetabular rim. The large-volume (14-mL) IP injection produced a similar flow pattern to the 7 mL injections, whereas the superficial peritendinous injection produced a contrast pattern consistent with intramuscular flow. Subsequent dissection confirmed bursal flow for the 14-mL injection, whereas the superficial peritendinous injection placed latex within the superficial portion of the IP muscle (ie, intramuscular)., Conclusions: Sonographically guided IP injections using an in-plane, lateral-to-medial technique place injectate into the IP bursa between the IP tendon and the acetabular rim. Within the limits of this cadaveric investigation, this sonographically guided 7-mL IP "bursa" injection may provide a minimum of 50% circumferential IP tendon coverage and approximately 5 cm of cephalad and caudad flow. There does not appear to be a peritendinous space deep to the IP tendon at the acetabular rim that is both outside the bursa and amenable to sonographically guided injection. Injections into the superficial aspect of the IP using 7-mL volumes may not deliver injectate deep to the IP tendon and therefore may represent a fundamentally different injection.